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News Article | April 21, 2017
Site: www.prnewswire.com

More than 10 million Honeywell turbochargers have been sold in China since the beginning of TS operations in China more than 20 years ago. Key launches in the past year include: the Buick Encore, Chevrolet Trax, Baojun 560/ 730, and the Chery TIGGO7. According to Honeywell's most recent Turbo Forecast, China will remain the highest growth market for turbocharged light vehicles. After a very strong fourth quarter in 2016, Honeywell has updated its forecast for China calling for a 20-point increase in turbo penetration of total sales. This means the annual sales of turbocharged light vehicles in China will increase from 10.6 million in 2016 to more than 16 million in 2021. On display in Shanghai will be Honeywell's Gasoline VNT Turbocharger, which features a variable geometry turbine stage rather than a typical wastegate valve to help achieve better fuel economy. Designed to work in tandem with a combustion phasing technology known as the Miller cycle, this turbo takes on more work and allows greater thermal efficiency in the engine. This results in improved fuel economy and reduced CO2 emissions at nearly all engine speeds. Honeywell has applied the performance-enhancing VNT technology to nearly 70 million turbos used with diesel engines during the past three decades. It is an industry first to apply VNT technology for the higher-temperature gasoline engine environment – suitable for high-production volume passenger vehicles – without resorting to expensive exotic materials. Honeywell Transportation Systems developed its latest VNT turbocharger for the Volkswagen Group's 1.5L gasoline engine to be used in various VW and Audi models. In its most recent benchmarking study, industry analyst FEV Group GmbH determined that the carbon dioxide emissions (108g/km) for a 1,250 kg vehicle with Honeywell's technology represents best-in-class performance for the industry in 2017. Honeywell is bringing a look into the future to its display, with three examples of electric boosting products that can help provide additional benefits for automakers to use in improving performance and meeting regulatory targets. These include: Honeywell expects these solutions will continue to grow in demand as electric and hybrid vehicles are expected to grow globally from a total of 3 million vehicles sold in 2016 to a total of 16 million sold annually by 2021. Within the electrified category, mild hybrids are expected to account for 46 percent of the mix, full hybrids will account for 40 percent; and pure electric vehicles will be most of the remaining 14 percent. Honeywell estimates 70 percent of all mild hybrid vehicles will have a turbo or multiple turbo systems (mechanical and electric). Honeywell will also offer a demo of three software initiatives aimed at diagnostics and prognostics of vehicle condition, automotive cyber security and calibration of vehicle powertrains. In addition to Honeywell's powertrain related technologies, Honeywell will showcase a new automotive refrigerant that achieves a 99.9 percent greenhouse gas emission reduction compared with previous generation refrigerants with the same or better cooling performance. Honeywell will also present a series of Reddot Award winning products including an indoor air purifier and indoor air quality meter. Honeywell is working with automakers on extending these air quality and environmentally friendly technologies to future vehicle cabin designs. "We pay great attention to the Chinese market and have formulated a long-term strategic plan in China," said Honeywell China President Stephen Shang. "Honeywell's goal is to be the best operating global company in China with best products, best quality, best value and fastest speed for our customers. Our turbocharging business is one of the best examples of how Honeywell is applying global innovations and experience to create a tailored local technology solution with fully local end-to-end capacity." "Our unique Honeywell automotive, aerospace and automation expertise allows us to innovate, bringing differentiated turbo technologies for conventional powertrains as well as electric boosting and Automotive Software solutions," said Charles Jin, Honeywell Transportation Systems Vice President and General Manager of High Growth Regions, China and India. "Moreover, we'll bring to the automotive world, innovative technologies that help make vehicles safer, more connected, more energy efficient and environmentally friendly." Honeywell Transportation Systems will be displaying its automotive solutions and conducting demos, tours and contests at Hall 4.2 booth #4B H001 during Auto Shanghai. Honeywell (www.honeywell.com) is a Fortune 100 software-industrial company that delivers industry specific solutions that include aerospace and automotive products and services; control technologies for buildings, homes, and industry; and performance materials globally. Our technologies help everything from aircraft, cars, homes and buildings, manufacturing plants, supply chains, and workers become more connected to make our world smarter, safer, and more sustainable. For more news and information on Honeywell, please visit www.honeywell.com/newsroom. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/honeywell-boosting-chinas-auto-industry-now-and-in-the-future-300443622.html


MARLBOROUGH, Mass.--(BUSINESS WIRE)--Sunovion Pharmaceuticals Inc. (Sunovion) presented data from the Phase 3 GOLDEN trials, showing that treatment with SUN-101/eFlow® significantly improved lung function, health related quality of life and respiratory symptoms among people with moderate-to-very severe chronic obstructive pulmonary disease (COPD), at the American Thoracic Society 2017 International Conference (ATS 2017) held May 19-24, 2017, in Washington D.C. Sunovion also presented data from the long-term safety trial showing a high rate of patient reported satisfaction and confidence with the use of the investigational eFlow® closed system nebulizer. “There are no approved nebulized, long-acting muscarinic antagonists (LAMAs) currently available for use in COPD,” said Thomas H. Goodin, Ph.D., Senior Director, Clinical Development at Sunovion. “These data suggest that for moderate-to-very severe patients, SUN-101/eFlow® could potentially be an effective and well-tolerated maintenance therapy.” If approved, SUN-101/eFlow® will be the first nebulized LAMA approved for the treatment of COPD in the U.S. The investigational eFlow® closed system nebulizer, developed by PARI Pharma GmbH, is portable, virtually silent, designed to deliver the medication in two to three minutes and, unlike handheld inhalers, allows patients to breathe normally while using the device. “COPD symptoms can severely impact patients’ daily activities and health related quality of life, and it is important for any treatment to be not only well-tolerated and effective, but also easy to administer,” said Gary Ferguson, M.D., Pulmonary Research Institute of Southeast Michigan and Principal Investigator for the GOLDEN-5 clinical trial. “With its efficacy and tolerability profile as well as the portability and short administration time, SUN-101/eFlow® could be a valuable treatment option for patients with COPD.” Results from three Phase 3 studies (GOLDEN-3, GOLDEN-4, GOLDEN-5) demonstrate the efficacy and safety of SUN-101/eFlow® in a population of patients with real-world characteristics representing its potential as an important maintenance therapy in patients with moderate-to-very severe COPD. Key data presented included: The expected action date by the U.S. Food and Drug Administration (FDA) under the Prescription Drug User Fee Act (PDUFA) for SUN-101/eFlow® is May 29, 2017. SUN-101 (glycopyrrolate) is a long-acting muscarinic antagonist (LAMA) bronchodilator delivered via the proprietary investigational eFlow® closed system nebulizer. SUN-101/eFlow® is currently in development as a nebulized treatment for patients with moderate-to-very-severe chronic obstructive pulmonary disease (COPD). The investigational combined product, consisting of SUN-101 and the investigational eFlow® closed system nebulizer, which has been optimized for SUN-101 delivery, has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of COPD. A long-acting muscarinic antagonist (LAMA) is a type of long-acting bronchodilator, along with long-acting beta agonists (LABAs). According to the GOLD report, these are currently the first-line standard of care maintenance therapy for symptomatic patients with COPD, and helps the muscles around the airways in lungs stay relaxed to prevent symptoms such as wheezing, coughing, chest tightness, and shortness of breath.1 LAMAs and LABAs are widely used and important therapeutic approaches for people with COPD. GOLDEN-3 and GOLDEN-4 were pivotal Phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter, efficacy and safety trials comparing SUN-101/eFlow® with placebo in adults with moderate-to-very severe COPD. The GOLDEN-3 trial enrolled 653 people who were at least 40 years old at 45 sites in the United States. The GOLDEN-4 trial enrolled 641 people who were at least 40 years old at 49 sites in the United States. SUN-101/eFlow® 25 mcg, SUN-101/eFlow® 50 mcg or placebo was administered twice daily in these studies. The primary endpoint was the change from baseline in trough FEV at Week 12. Secondary endpoints included standardized change from baseline at Week 12 in FEV area under the curve (AUC), change from baseline in trough forced vital capacity (FVC) at Week 12, change from baseline in health status measured by St. George’s Respiratory Questionnaire and change in rescue medication use. Safety was assessed by the number of treatment-emergent adverse events (TEAE), serious adverse events (SAE) or major adverse cardiac events (MACE) and the number and percentage of study participants who discontinued the study due to TEAE. Both GOLDEN-3 and GOLDEN-4 studies included not only patients who were taking effective background long acting bronchodilator therapy but also patients with very severe disease and co-existing cardiovascular illness. Approximately 10 percent of the population were elderly (>75 years), 65 percent were classified as being high-risk cardiovascular patients and approximately 30 percent were taking long acting bronchodilator therapy [NCT02347761 and NCT02347774]. GOLDEN-5 was a Phase 3, 48-week, randomized, open-label, active-controlled, parallel-group, multicenter safety trial designed to evaluate the long term safety and tolerability of SUN-101/eFlow® in adults with moderate-to-very severe COPD. The study enrolled 1,087 patients at 111 investigational sites in the United States and Europe. The study evaluated 50 mcg of SUN-101/eFlow® delivered twice-daily and active comparator 18 mcg of Spiriva® (tiotropium bromide) delivered once-daily by the HandiHaler® device. The primary safety endpoints were: the number and percentage of study participants with treatment-emergent adverse events (TEAE), the number and percentage of study participants with treatment-emergent serious adverse events (SAE), the number and percentage of study participants who discontinued the study due to TEAEs and the number and incidence of subjects with MACE. The secondary endpoint was the mean change from baseline over 48 weeks in trough FEV for all subjects. The study included not only patients who were taking effective background long acting bronchodilator therapy but also patients with very severe disease and co-existing significant cardiovascular illness. Approximately 10 percent of the population were elderly (>75 years), 65 percent were classified as being high-risk cardiovascular patients and more than 40 percent were taking long acting bronchodilator therapy [NCT02276222]. Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or lung abnormalities usually caused by significant exposure to toxic particles or gases. The main risk factor for COPD is tobacco smoking, but other environmental exposures may contribute.1 Approximately 15.7 million adults in the U.S. report that they have been diagnosed with COPD.2 It is estimated that several million more adults have undiagnosed COPD.3 COPD is responsible for over 120,000 deaths per year, making it the third leading cause of death in the U.S.2 COPD develops slowly and the symptoms often worsen over time, potentially limiting the ability to perform routine activities.2 Symptoms of COPD include coughing, wheezing, shortness of breath, excess production of mucus in the lungs, the inability to breathe deeply and the feeling of being unable to breathe.4 The symptoms of COPD can be most severe during the night and early morning.5 Morning symptoms can be associated with limitation of activities during the day, impaired health status and increased risk of exacerbation.6 Night-time symptoms disturb sleep, reduce sleep quality and, in the long term, may be associated with development or worsening of cardiovascular diseases, cognition, depression and increased mortality.7 Sunovion is committed to expanding its heritage of advancing new treatments for serious respiratory medical conditions, including the 15.7 million people in the U.S. who are living with chronic obstructive pulmonary disease (COPD).2 The company offers the broadest COPD portfolio in the U.S., providing treatment options for people at various stages of COPD, as well as the flexibility to choose handheld or nebulized delivery based on individual needs. Sunovion goes beyond treatment offerings to support awareness and understanding with the entire COPD community – health care providers, patients and caregivers – and to advancing disease state education through its partnerships with various organizations. Sunovion is a global biopharmaceutical company focused on the innovative application of science and medicine to help people with serious medical conditions. Sunovion’s vision is to lead the way to a healthier world. The company’s spirit of innovation is driven by the conviction that scientific excellence paired with meaningful advocacy and relevant education can improve lives. With patients at the center of everything it does, Sunovion has charted new paths to life-transforming treatments that reflect ongoing investments in research and development and an unwavering commitment to support people with psychiatric, neurological and respiratory conditions. Sunovion’s track record of discovery, development and commercialization of important therapies has included Utibron™ Neohaler® (indacaterol/glycopyrrolate) inhalation powder, Brovana® (arformoterol tartrate) inhalation solution, Latuda® (lurasidone HCI) and Aptiom® (eslicarbazepine acetate). Headquartered in Marlborough, Mass., Sunovion is an indirect, wholly-owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd. Sunovion Pharmaceuticals Europe Ltd., based in London, England, Sunovion Pharmaceuticals Canada Inc., based in Mississauga, Ontario, and Sunovion CNS Development Canada ULC, based in Toronto, Ontario, are wholly-owned direct subsidiaries of Sunovion Pharmaceuticals Inc. Additional information can be found on the company’s web sites: www.sunovion.com, www.sunovion.eu and www.sunovion.ca. Connect with Sunovion on Twitter, LinkedIn, Facebook and YouTube. About Sumitomo Dainippon Pharma Co., Ltd. Sumitomo Dainippon Pharma is among the top-ten listed pharmaceutical companies in Japan operating globally in major pharmaceutical markets, including Japan, the United States, China and the European Union. Sumitomo Dainippon Pharma aims to create innovative pharmaceutical products in the Psychiatry & Neurology area and the Oncology area, which have been designated as the focus therapeutic areas. Sumitomo Dainippon Pharma is based on the merger in 2005 between Dainippon Pharmaceutical Co., Ltd., and Sumitomo Pharmaceuticals Co., Ltd. Today, Sumitomo Dainippon Pharma has about 6,500 employees worldwide. Additional information about Sumitomo Dainippon Pharma is available through its corporate website at www.ds-pharma.com. LATUDA and SUNOVION are registered trademarks of Sumitomo Dainippon Pharma Co., Ltd. BROVANA is a registered trademark of Sunovion Pharmaceuticals Inc. APTIOM is used under license from Bial. ARCAPTA and NEOHALER are registered trademarks of Novartis AG, used under license. SEEBRI and UTIBRON are trademarks of Novartis AG, used under license. eFlow® is a registered trademark of PARI Pharma GmbH. Spiriva® and HandiHaler® are registered trademarks of Boehringer Ingelheim Pharma GMBH & Co KG. Sunovion Pharmaceuticals Inc. is a U.S. subsidiary of Sumitomo Dainippon Pharma Co., Ltd. For a copy of this release, visit Sunovion’s web site at www.sunovion.com 1 GOLD Guidelines 2017. http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html. Accessed: March 16, 2017. 2 MMWR: Morbidity and Mortality Weekly Report. Employment and Activity Limitations Among Adults with Chronic Obstructive Pulmonary Disease — United States, 2013. March 27, 2015; 64(11). Available at http://www.cdc.gov/mmwr/ 3 National Heart, Lung, and Blood Institute. “What is COPD?” Available at: http://www.nhlbi.nih.gov/health/educational/copd/what-is-copd/index.htm. Accessed: March 2, 2016 4 National Heart, Lung and Blood Institute. (2013). What Are the Signs and Symptoms of COPD? Retrieved from https://www.nhlbi.nih.gov/health/health-topics/topics/copd/signs. 5 Partridge MR, Karlsson N, Small IR. Patient insight into the impact of chronic obstructive pulmonary disease in the morning: an internet survey. Curr Med Res Opin. 2009;25:2043–8. 6 Roche N, Small M, Broomfield S, Higgins V, Pollard R. Real world COPD: association of morning symptoms with clinical and patient reported outcomes. COPD. 2013;10:679–86. 7 Agusti A, Hedner J, Marin JM, Barbé F, Cazzola M, Rennard S. Night-time symptoms: a forgotten dimension of COPD. Eur Respir Rev. 2011;20:183–94.


WASHINGTON & REDWOOD CITY, Calif.--(BUSINESS WIRE)--Pulmonx®, Inc. today announced the results of two multi-center, randomized clinical trials showing clinically meaningful improvements in lung function after treatment with the Zephyr® Endobronchial Valve (EBV) in emphysema patients without collateral ventilation. Six-month data from both the TRANSFORM and IMPACT trials, presented this week at the American Thoracic Society international conference, demonstrate that Zephyr valves provide positive benefits in these patients with either homogeneous or heterogeneous distribution of emphysema. Zephyr Endobronchial Valves are tiny, minimally-invasive, one-way valves placed via a flexible bronchoscope in airways of the lungs to occlude diseased regions and reduce lung hyperinflation. As a result, the remaining healthier regions can function more efficiently, enabling better breathing and an improved quality of life for patients. In the clinical trials, patients were selected based on the absence of collateral ventilation (airflow between regions of the lung that bypasses normal airways), which was assessed in the trials using the Chartis Pulmonary Assessment System from Pulmonx. The effectiveness of endobronchial valves is dependent on selection of an area of the lung without collateral ventilation for treatment. The TRANSFORM study, a multi-center, prospective, randomized, controlled trial, evaluated 97 patients with heterogeneous (more focally-distributed) emphysema at 17 centers in six countries. Patients were randomized 2:1 to Zephyr valve treatment versus standard of care. The authors concluded that Zephyr valve treatment in heterogeneous emphysema patients without collateral ventilation confers clinically and statistically significant sustained benefits, with improvements in lung function, exercise capacity and quality of life. At six months, 56.3 percent of patients treated with Zephyr valves achieved a 12 percent or greater improvement in lung function (FEV ) from baseline, when compared to 3.2 percent of patients in the control group. The lung function (FEV ) in the Zephyr valve-treated group was on average 29.3 percent higher than the control group. Improvements of a similar magnitude were observed between groups in exercise capacity (measured by Six-Minute Walk Distance, or 6MWD), with Zephyr valve-treated patients improving upon the control group by 78.7 meters. Finally, the quality of life of Zephyr valve treated patients improved by 6.5 points over control in the St. Georges Respiratory Questionnaire (SGRQ) score. “The magnitude of benefits to patients in this pan-European trial are dramatic and reinforce results published from prior single center studies,” said Samuel Kemp, MD, principal investigator and respiratory physician at the Royal Brompton Hospital, London, UK. “Using Chartis for patient selection enabled us to accurately identify patients without collateral ventilation, which is a key predictor for good outcomes with this device.” The IMPACT study enrolled 93 patients with severe homogeneous (more diffusely-distributed) emphysema who were randomized 1:1 to Zephyr valve treatment versus medical management. Consistent with the previously published three-month data, the improvements remained statistically and clinically significant at six months with Zephyr valve treated patients experiencing improvements over control for FEV of 16.3 percent (p<0.001), an increase in 6MWD of 28.3 meters (p=0.016), and an improvement in the quality of life based on a decrease in the SGRQ score of –7.5 points (p<0.001). The most common side effect of the Zephyr valves in both studies was pneumothorax (20 to 26 percent in the treated group) and chronic obstructive pulmonary disease exacerbations (11 to 28 percent versus 6 to 18 percent in the control group) in the immediate post-procedure period. Both were addressed with standard medical management. Two prior randomized controlled trials of the Zephyr valve in patients without collateral ventilation (the STELVIO and BeLieVeR-HIFi trials) also support the ability of Zephyr valves to significantly improve lung function, exercise tolerance and quality of life.1,2 Additional published clinical data demonstrate sustained patient benefits out to five years3 and suggest potential survival benefits at five and 10 years post-treatment,4,5 indicating a possible slowing in disease progression. “For patients with severe emphysema, there were previously few therapeutic options,” said Pulmonx Chief Executive Officer Glen French. “Now, we have consistent data from four randomized studies showing that, regardless of disease heterogeneity, when patients are selected for the absence of collateral ventilation, they can gain substantial benefits in quality of life, exercise capacity and lung function with Zephyr valves.” Over the past 10 years, approximately 50,000 Zephyr EBVs have been implanted globally in more than 12,000 patients. To view a video of the Zephyr EBV procedure, click here. Based in Redwood City, California, and Neuchâtel, Switzerland, Pulmonx is an interventional pulmonology company focused on developing life-changing, cost-effective technologies that improve the lives of patients suffering from lung disease worldwide. For more information, visit www.pulmonx.com. The Zephyr Endobronchial Valve is an investigational device in the United States. Limited by U.S. law to investigational use only.


Researchers presented new data from the completed three-month Phase 3 studies, which included more than 1,250 patients with moderate to very severe COPD, in two separate presentations at the 2017 ATS meeting. The first presentation, which focused on efficacy outcomes, demonstrated statistically significant and clinically meaningful improvements over placebo in trough forced expiratory volume in one second (FEV ) and in overall treatment effect on trough FEV (OTE FEV ) after 12 weeks of dosing in each study and for each of the revefenacin doses studied (88 mcg once daily and 175 mcg once daily). The improvements in trough FEV , the primary efficacy endpoint, versus placebo for the intent-to-treat populations across both studies were 118 mL and 145 mL for 88 mcg and 175 mcg, respectively (p ≤ 0.001). Additionally, the improvements in OTE FEV , a key secondary endpoint, versus placebo for the intent-to-treat population across both studies were 112 mL and 139 mL for 88 mcg and 175 mcg, respectively (p ≤ 0.001). The second presentation featured safety and tolerability data from the two completed three-month Phase 3 studies. Both doses of revefenacin had comparable rates of adverse events to placebo, low rates of serious adverse events, and no clinically meaningful differences in blood parameters or electrocardiogram (ECG) data, across all treatment groups (active and placebo). As previously reported, the most commonly reported adverse events, across both trials and across all treatment groups, were exacerbations, cough, dyspnea and headache. There were no reports of blurred vision, narrow-angle glaucoma or worsening of urinary retention. Reports of dry mouth were <0.5% in the revefenacin treatment arms. "These presentations build upon the topline results that we announced last October and further confirm that revefenacin may offer meaningful benefits to patients with moderate to very severe COPD," said Brett Haumann, MD, Chief Medical Officer at Theravance Biopharma. "We believe that these results position revefenacin favorably as a potentially key therapeutic option for COPD patients if approved, particularly as revefenacin would represent the first once-daily nebulized bronchodilator for COPD. We anticipate completing the ongoing Phase 3 safety trial of revefenacin in mid-2017 with the goal of filing an NDA by the end of 2017." Mylan President Rajiv Malik commented, "We continue to be very pleased with the progress of the Phase 3 revefenacin program, and are excited to have the opportunity to showcase this important data set at ATS for the first time. According to the GOLD Guidelines for COPD, LAMAs are a cornerstone of therapy for moderate to severe COPD, yet there are currently no nebulized LAMAs available. We believe this product has the potential to help address an unmet medical need for patients. Further, revefenacin represents a key contributor in Mylan's pipeline of promising respiratory products, and supports the growth of our respiratory franchise. If approved, we believe that we are well-positioned to support the commercial success of this product." Revefenacin is being developed as a once-daily, nebulized bronchodilator for the treatment of patients with COPD and will be compatible with a range of jet nebulizers. The three-month Phase 3 pivotal studies were replicate, randomized, double-blind, placebo-controlled, parallel-group trials designed to provide pivotal efficacy and safety data for once-daily revefenacin over a dosing period of 12 weeks. The replicate studies enrolled a combined total of over 1,250 patients in the U.S. across a range of disease severity from moderate to very severe COPD and allowed for the concomitant use of long-acting beta agonist (LABA) and/or long-acting beta agonist/inhaled corticosteroid (LABA/ICS) products in a significant proportion (38%) of the studied population. Study investigators tested two doses (88 mcg and 175 mcg) of revefenacin inhalation solution or matched placebo administered once daily via a standard jet nebulizer in moderate to very severe COPD patients. The revefenacin Phase 3 program also includes an ongoing 12-month, open-label, active comparator safety study in more than 1,050 patients, which is expected to be completed in mid-2017. Together, the three studies enrolled approximately 2,300 patients. Should outcomes from the safety study be supportive, Theravance Biopharma expects to file a New Drug Application (NDA) for revefenacin with the U.S. Food and Drug Administration (FDA) by the end of 2017. Theravance Biopharma and its affiliates have partnered with Mylan and its affiliates on the development and commercialization of nebulized revefenacin products for COPD and other respiratory diseases. In a separate presentation at 2017 ATS, researchers reported baseline data on the prevalence of COPD patients with low peak inspiratory flow rate (PIFR) who are enrolled in the ongoing 12-month, open-label, active comparator safety study of revefenacin. Of the total population of 1,080 patients who were enrolled in the study, 448 patients had their PIFR measured using a commercially available, easy-to-use instrument (InCheck®) at the time of study randomization. Researchers categorized PIFRs of less than 40 L/min against the resistance of the Handihaler® as "low" for the means of this analysis based upon published research and reference data. Presented results showed that 24% of subjects had a low PIFR rate at the time of randomization. Analysis of patient characteristics showed that patients with a low PIFR tended to be female and exhibited evidence of more severe COPD, although a proportion of patients with less severe COPD were also found to have low PIFR. "Patients with low PIFR may not be able to breathe in with enough force to benefit from the use of handheld COPD devices. There is growing evidence that these patients may have better short-term and long-term benefits from nebulized therapy. This is supported by a recent scientific study that reported that patients with low PIFR, regardless of disease severity, showed statistically significant lower COPD hospital readmission rates within both 30 and 90 days when using nebulized therapy as compared to a handheld product following COPD exacerbation1," said Dr. Haumann. "We believe that revefenacin could provide a unique benefit to patients with low PIFR and are currently evaluating this in a dedicated clinical study." Researchers also presented results from a study highlighting the pharmacological properties of revefenacin in isolated tissue airways, from both rats and humans, to enable preclinical to clinical translation of the in vivo findings in rats. Study data demonstrated that revefenacin produced potent and persistent anti-muscarinic activity in the airway tissues of both rats and humans. These translational findings are consistent with clinical data from the replicate three-month Phase 3 studies of revefenacin demonstrating 24-hour bronchodilatory effects in COPD patients. Theravance Biopharma and Mylan N.V. and their respective affiliates have established a strategic collaboration to develop and commercialize nebulized revefenacin products for COPD and other respiratory diseases. Under the terms of the agreement, Theravance Biopharma is leading the U.S. development program for the revefenacin inhalation solution product, with all costs reimbursed by Mylan up until the approval of the first new drug application, after which costs will be shared. Mylan is responsible for ex-U.S. development and commercialization. Theravance Biopharma is eligible to receive up to $220 million in development and sales milestone payments, as well as a profit-sharing arrangement with Mylan on U.S. sales and double-digit royalties on ex-U.S. sales. Additionally, Theravance Biopharma retains worldwide rights to revefenacin delivered through other dosage forms, such as a metered dose inhaler or dry powder inhaler (MDI/DPI), and the rights to nebulized revefenacin in China. COPD is a growing and devastating disease that is the third leading cause of death in the U.S.2 An estimated 12.7 million American adults are diagnosed with COPD and an almost equal number are believed to be undiagnosed.3There were more than 700,000 hospital discharges related to COPD in the U.S. reported in 2010. The costs of managing COPD in the U.S. were estimated to be nearly $50 billion in 2010, including $29.5 billion in direct healthcare expenditures, $8 billion in indirect morbidity costs and $12.4 billion in indirect mortality costs.3 Revefenacin (TD-4208) is a novel investigational once-daily nebulized LAMA in Phase 3 development for the treatment of moderate to very severe COPD. Market research by Theravance Biopharma indicates approximately 9% of the treated COPD patients in the U.S. use nebulizers for ongoing maintenance therapy.4 LAMAs are a cornerstone of maintenance therapy for COPD and, if approved, revefenacin would provide a once-daily option for COPD patients who require, or prefer, nebulized therapy. The product's stability in both metered dose inhaler and dry powder device formulations suggest that this LAMA could also serve as a foundation for novel handheld combination products. Theravance Biopharma is a diversified biopharmaceutical company with the core purpose of creating medicines that help improve the lives of patients suffering from serious illness. Our pipeline of internally discovered product candidates includes potential best-in-class medicines to address the unmet needs of patients being treated for serious conditions primarily in the acute care setting. VIBATIV® (telavancin), our first commercial product, is a once-daily dual-mechanism antibiotic approved in the U.S., Europe and certain other countries for certain difficult-to-treat infections. Revefenacin (TD-4208) is a long-acting muscarinic antagonist (LAMA) being developed as a potential once-daily, nebulized treatment for chronic obstructive pulmonary disease (COPD). Our neprilysin (NEP) inhibitor program is designed to develop selective NEP inhibitors for the treatment of a range of major cardiovascular and renal diseases, including acute and chronic heart failure, hypertension and chronic kidney diseases, such as diabetic nephropathy. Our research efforts are focused in the areas of inflammation and immunology, with the goal of designing medicines that provide targeted drug delivery to tissues in the lung and gastrointestinal tract in order to maximize patient benefit and minimize risk. The first program to emerge from this research is designed to develop intestinally restricted pan-Janus kinase (JAK) inhibitors for the treatment of a range of inflammatory intestinal diseases. In addition, we have an economic interest in future payments that may be made by Glaxo Group Limited or one of its affiliates (GSK) pursuant to its agreements with Innoviva, Inc. relating to certain drug development programs, including the Closed Triple (the combination of fluticasone furoate, umeclidinium, and vilanterol), currently in development for the treatment of COPD and asthma. For more information, please visit www.theravance.com. THERAVANCE®, the Cross/Star logo, and VIBATIV® are registered trademarks of the Theravance Biopharma group of companies. Trademarks, trade names or service marks of other companies appearing on this press release are the property of their respective owners. This press release contains certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, expectations and future events. Theravance Biopharma intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to: the company's strategies, plans and objectives, the company's regulatory strategies and timing of clinical studies, the potential benefits and mechanisms of action of the company's product and product candidates, the company's expectations for product candidates through development, potential regulatory approval and commercialization (including their potential as components of combination therapies) and the company's expectations for product sales. These statements are based on the current estimates and assumptions of the management of Theravance Biopharma as of the date of the press release and the conference call and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance Biopharma to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: delays or difficulties in commencing or completing clinical studies, the potential that results from clinical or non-clinical studies indicate the company's product candidates are unsafe or ineffective (including when our product candidates are studied in combination with other compounds),the feasibility of undertaking future clinical trials for our product candidates based on FDA policies and feedback, dependence on third parties to conduct clinical studies, delays or failure to achieve and maintain regulatory approvals for product candidates, risks of collaborating with or relying on third parties to discover, develop and commercialize product and product candidates, and risks associated with establishing and maintaining sales, marketing and distribution capabilities with appropriate technical expertise and supporting infrastructure. Other risks affecting Theravance Biopharma are described under the heading "Risk Factors" contained in Theravance Biopharma's Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 9, 2017 and Theravance Biopharma's other filings with the SEC. In addition to the risks described above and in Theravance Biopharma's filings with the SEC, other unknown or unpredictable factors also could affect Theravance Biopharma's results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance Biopharma assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law. Mylan is a global pharmaceutical company committed to setting new standards in healthcare. Working together around the world to provide 7 billion people access to high quality medicine, we innovate to satisfy unmet needs; make reliability and service excellence a habit; do what's right, not what's easy; and impact the future through passionate global leadership. We market a growing portfolio of approximately 7,500 products around the world, including antiretroviral therapies on which approximately 50% of people being treated for HIV/AIDS in the developing world depend. We market our products in more than 165 countries and territories. We are one of the world's largest producers of active pharmaceutical ingredients. Every member of our more than 35,000-strong workforce is dedicated to creating better health for a better world, one person at a time. Learn more at mylan.com. This press release includes statements that constitute "forward-looking statements," including with regard to revefenacin having the potential to offer meaningful benefits to patients with moderate to very severe COPD; revefenacin being positioned favorably as a potentially key therapeutic option for COPD patients if approved, particularly as revefenacin would represent the first once-daily nebulized bronchodilator for COPD; anticipated completion of the ongoing Phase 3 safety trial of revefenacin in mid-2017 with the goal of filing an NDA by the end of 2017; revefenacin having the potential to help address an unmet medical need for patients; revefenacin representing a key contributor in Mylan's pipeline of promising respiratory products, and supporting the growth of Mylan's respiratory franchise; Mylan's belief that it is well-positioned to support the commercial success of the product; the ongoing 12-month, open-label, active comparator safety study in more than 1,050 patients, which is expected to be completed in mid-2017; Theravance Biopharma expecting to file a New Drug Application (NDA) for revefenacin with the U.S. Food and Drug Administration (FDA) by the end of 2017; the possibility that revefenacin could provide a unique benefit to patients with low PIFR; and the possibility that this LAMA could also serve as a foundation for novel handheld combination products. These statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Because such statements inherently involve risks and uncertainties, actual future results may differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to: success of clinical trials and our and our partners' ability to execute on new product opportunities; any regulatory, legal or other impediments to our ability to bring our and our partners' products to market; other risks inherent in product development; the scope, timing, and outcome of any ongoing legal proceedings, including government investigations, and the impact of any such proceedings on our or our partners' business; actions and decisions of healthcare and pharmaceutical regulators, and changes in healthcare and pharmaceutical laws and regulations, in the United States and abroad; the impact of competition; strategies by competitors or other third parties to delay or prevent product introductions; the effect of any changes in our customer and supplier relationships and customer purchasing patterns; any other changes in third-party relationships; changes in the economic and financial conditions of  the businesses of Mylan; uncertainties and matters beyond the control of management; and the other risks detailed in Mylan's filings with the Securities and Exchange Commission. Mylan undertakes no obligation to update these statements for revisions or changes after the date of this release. 1 Loh CH, Lovings T, Ohar J. Long acting nebulized agents decrease readmissions in patients with suboptimal peak inspiratory flow. Chest 2016;150:925A–925A. 2American Lung Association. "Chronic Obstructive Pulmonary Disease (COPD)" http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/copd. 3 American Lung Association. "Trends in COPD (Chronic Bronchitis and Emphysema): Morbidity and Mortality" http://www.lung.org/assets/documents/research/copd-trend-report.pdf. 4 TBPH market research (N = 160 physicians); Refers to US COPD patients To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/theravance-biopharma-and-mylan-report-additional-phase-3-data-for-revefenacin-td-4208-in-several-presentations-at-2017-ats-300461835.html


Researchers presented new data from the completed three-month Phase 3 studies, which included more than 1,250 patients with moderate to very severe COPD, in two separate presentations at the 2017 ATS meeting. The first presentation, which focused on efficacy outcomes, demonstrated statistically significant and clinically meaningful improvements over placebo in trough forced expiratory volume in one second (FEV ) and in overall treatment effect on trough FEV (OTE FEV ) after 12 weeks of dosing in each study and for each of the revefenacin doses studied (88 mcg once daily and 175 mcg once daily). The improvements in trough FEV , the primary efficacy endpoint, versus placebo for the intent-to-treat populations across both studies were 118 mL and 145 mL for 88 mcg and 175 mcg, respectively (p ≤ 0.001). Additionally, the improvements in OTE FEV , a key secondary endpoint, versus placebo for the intent-to-treat population across both studies were 112 mL and 139 mL for 88 mcg and 175 mcg, respectively (p ≤ 0.001). The second presentation featured safety and tolerability data from the two completed three-month Phase 3 studies. Both doses of revefenacin had comparable rates of adverse events to placebo, low rates of serious adverse events, and no clinically meaningful differences in blood parameters or electrocardiogram (ECG) data, across all treatment groups (active and placebo). As previously reported, the most commonly reported adverse events, across both trials and across all treatment groups, were exacerbations, cough, dyspnea and headache. There were no reports of blurred vision, narrow-angle glaucoma or worsening of urinary retention. Reports of dry mouth were <0.5% in the revefenacin treatment arms. "These presentations build upon the topline results that we announced last October and further confirm that revefenacin may offer meaningful benefits to patients with moderate to very severe COPD," said Brett Haumann, MD, Chief Medical Officer at Theravance Biopharma. "We believe that these results position revefenacin favorably as a potentially key therapeutic option for COPD patients if approved, particularly as revefenacin would represent the first once-daily nebulized bronchodilator for COPD. We anticipate completing the ongoing Phase 3 safety trial of revefenacin in mid-2017 with the goal of filing an NDA by the end of 2017." Mylan President Rajiv Malik commented, "We continue to be very pleased with the progress of the Phase 3 revefenacin program, and are excited to have the opportunity to showcase this important data set at ATS for the first time. According to the GOLD Guidelines for COPD, LAMAs are a cornerstone of therapy for moderate to severe COPD, yet there are currently no nebulized LAMAs available. We believe this product has the potential to help address an unmet medical need for patients. Further, revefenacin represents a key contributor in Mylan's pipeline of promising respiratory products, and supports the growth of our respiratory franchise. If approved, we believe that we are well-positioned to support the commercial success of this product." Revefenacin is being developed as a once-daily, nebulized bronchodilator for the treatment of patients with COPD and will be compatible with a range of jet nebulizers. The three-month Phase 3 pivotal studies were replicate, randomized, double-blind, placebo-controlled, parallel-group trials designed to provide pivotal efficacy and safety data for once-daily revefenacin over a dosing period of 12 weeks. The replicate studies enrolled a combined total of over 1,250 patients in the U.S. across a range of disease severity from moderate to very severe COPD and allowed for the concomitant use of long-acting beta agonist (LABA) and/or long-acting beta agonist/inhaled corticosteroid (LABA/ICS) products in a significant proportion (38%) of the studied population. Study investigators tested two doses (88 mcg and 175 mcg) of revefenacin inhalation solution or matched placebo administered once daily via a standard jet nebulizer in moderate to very severe COPD patients. The revefenacin Phase 3 program also includes an ongoing 12-month, open-label, active comparator safety study in more than 1,050 patients, which is expected to be completed in mid-2017. Together, the three studies enrolled approximately 2,300 patients. Should outcomes from the safety study be supportive, Theravance Biopharma expects to file a New Drug Application (NDA) for revefenacin with the U.S. Food and Drug Administration (FDA) by the end of 2017. Theravance Biopharma and its affiliates have partnered with Mylan and its affiliates on the development and commercialization of nebulized revefenacin products for COPD and other respiratory diseases. In a separate presentation at 2017 ATS, researchers reported baseline data on the prevalence of COPD patients with low peak inspiratory flow rate (PIFR) who are enrolled in the ongoing 12-month, open-label, active comparator safety study of revefenacin. Of the total population of 1,080 patients who were enrolled in the study, 448 patients had their PIFR measured using a commercially available, easy-to-use instrument (InCheck®) at the time of study randomization. Researchers categorized PIFRs of less than 40 L/min against the resistance of the Handihaler® as "low" for the means of this analysis based upon published research and reference data. Presented results showed that 24% of subjects had a low PIFR rate at the time of randomization. Analysis of patient characteristics showed that patients with a low PIFR tended to be female and exhibited evidence of more severe COPD, although a proportion of patients with less severe COPD were also found to have low PIFR. "Patients with low PIFR may not be able to breathe in with enough force to benefit from the use of handheld COPD devices. There is growing evidence that these patients may have better short-term and long-term benefits from nebulized therapy. This is supported by a recent scientific study that reported that patients with low PIFR, regardless of disease severity, showed statistically significant lower COPD hospital readmission rates within both 30 and 90 days when using nebulized therapy as compared to a handheld product following COPD exacerbation1," said Dr. Haumann. "We believe that revefenacin could provide a unique benefit to patients with low PIFR and are currently evaluating this in a dedicated clinical study." Researchers also presented results from a study highlighting the pharmacological properties of revefenacin in isolated tissue airways, from both rats and humans, to enable preclinical to clinical translation of the in vivo findings in rats. Study data demonstrated that revefenacin produced potent and persistent anti-muscarinic activity in the airway tissues of both rats and humans. These translational findings are consistent with clinical data from the replicate three-month Phase 3 studies of revefenacin demonstrating 24-hour bronchodilatory effects in COPD patients. Theravance Biopharma and Mylan N.V. and their respective affiliates have established a strategic collaboration to develop and commercialize nebulized revefenacin products for COPD and other respiratory diseases. Under the terms of the agreement, Theravance Biopharma is leading the U.S. development program for the revefenacin inhalation solution product, with all costs reimbursed by Mylan up until the approval of the first new drug application, after which costs will be shared. Mylan is responsible for ex-U.S. development and commercialization. Theravance Biopharma is eligible to receive up to $220 million in development and sales milestone payments, as well as a profit-sharing arrangement with Mylan on U.S. sales and double-digit royalties on ex-U.S. sales. Additionally, Theravance Biopharma retains worldwide rights to revefenacin delivered through other dosage forms, such as a metered dose inhaler or dry powder inhaler (MDI/DPI), and the rights to nebulized revefenacin in China. COPD is a growing and devastating disease that is the third leading cause of death in the U.S.2 An estimated 12.7 million American adults are diagnosed with COPD and an almost equal number are believed to be undiagnosed.3 There were more than 700,000 hospital discharges related to COPD in the U.S. reported in 2010. The costs of managing COPD in the U.S. were estimated to be nearly $50 billion in 2010, including $29.5 billion in direct healthcare expenditures, $8 billion in indirect morbidity costs and $12.4 billion in indirect mortality costs.3 Revefenacin (TD-4208) is a novel investigational once-daily nebulized LAMA in Phase 3 development for the treatment of moderate to very severe COPD. Market research by Theravance Biopharma indicates approximately 9% of the treated COPD patients in the U.S. use nebulizers for ongoing maintenance therapy.4 LAMAs are a cornerstone of maintenance therapy for COPD and, if approved, revefenacin would provide a once-daily option for COPD patients who require, or prefer, nebulized therapy. The product's stability in both metered dose inhaler and dry powder device formulations suggest that this LAMA could also serve as a foundation for novel handheld combination products. Theravance Biopharma is a diversified biopharmaceutical company with the core purpose of creating medicines that help improve the lives of patients suffering from serious illness. Our pipeline of internally discovered product candidates includes potential best-in-class medicines to address the unmet needs of patients being treated for serious conditions primarily in the acute care setting. VIBATIV® (telavancin), our first commercial product, is a once-daily dual-mechanism antibiotic approved in the U.S., Europe and certain other countries for certain difficult-to-treat infections. Revefenacin (TD-4208) is a long-acting muscarinic antagonist (LAMA) being developed as a potential once-daily, nebulized treatment for chronic obstructive pulmonary disease (COPD). Our neprilysin (NEP) inhibitor program is designed to develop selective NEP inhibitors for the treatment of a range of major cardiovascular and renal diseases, including acute and chronic heart failure, hypertension and chronic kidney diseases, such as diabetic nephropathy. Our research efforts are focused in the areas of inflammation and immunology, with the goal of designing medicines that provide targeted drug delivery to tissues in the lung and gastrointestinal tract in order to maximize patient benefit and minimize risk. The first program to emerge from this research is designed to develop intestinally restricted pan-Janus kinase (JAK) inhibitors for the treatment of a range of inflammatory intestinal diseases. In addition, we have an economic interest in future payments that may be made by Glaxo Group Limited or one of its affiliates (GSK) pursuant to its agreements with Innoviva, Inc. relating to certain drug development programs, including the Closed Triple (the combination of fluticasone furoate, umeclidinium, and vilanterol), currently in development for the treatment of COPD and asthma. For more information, please visit www.theravance.com. THERAVANCE®, the Cross/Star logo, and VIBATIV® are registered trademarks of the Theravance Biopharma group of companies. Trademarks, trade names or service marks of other companies appearing on this press release are the property of their respective owners. This press release contains certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, expectations and future events. Theravance Biopharma intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to: the company's strategies, plans and objectives, the company's regulatory strategies and timing of clinical studies, the potential benefits and mechanisms of action of the company's product and product candidates, the company's expectations for product candidates through development, potential regulatory approval and commercialization (including their potential as components of combination therapies) and the company's expectations for product sales. These statements are based on the current estimates and assumptions of the management of Theravance Biopharma as of the date of the press release and the conference call and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance Biopharma to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: delays or difficulties in commencing or completing clinical studies, the potential that results from clinical or non-clinical studies indicate the company's product candidates are unsafe or ineffective (including when our product candidates are studied in combination with other compounds),the feasibility of undertaking future clinical trials for our product candidates based on FDA policies and feedback, dependence on third parties to conduct clinical studies, delays or failure to achieve and maintain regulatory approvals for product candidates, risks of collaborating with or relying on third parties to discover, develop and commercialize product and product candidates, and risks associated with establishing and maintaining sales, marketing and distribution capabilities with appropriate technical expertise and supporting infrastructure. Other risks affecting Theravance Biopharma are described under the heading "Risk Factors" contained in Theravance Biopharma's Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 9, 2017 and Theravance Biopharma's other filings with the SEC. In addition to the risks described above and in Theravance Biopharma's filings with the SEC, other unknown or unpredictable factors also could affect Theravance Biopharma's results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance Biopharma assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law. Mylan is a global pharmaceutical company committed to setting new standards in healthcare. Working together around the world to provide 7 billion people access to high quality medicine, we innovate to satisfy unmet needs; make reliability and service excellence a habit; do what's right, not what's easy; and impact the future through passionate global leadership. We market a growing portfolio of approximately 7,500 products around the world, including antiretroviral therapies on which approximately 50% of people being treated for HIV/AIDS in the developing world depend. We market our products in more than 165 countries and territories. We are one of the world's largest producers of active pharmaceutical ingredients. Every member of our more than 35,000-strong workforce is dedicated to creating better health for a better world, one person at a time. Learn more at mylan.com. This press release includes statements that constitute "forward-looking statements," including with regard to revefenacin having the potential to offer meaningful benefits to patients with moderate to very severe COPD; revefenacin being positioned favorably as a potentially key therapeutic option for COPD patients if approved, particularly as revefenacin would represent the first once-daily nebulized bronchodilator for COPD; anticipated completion of the ongoing Phase 3 safety trial of revefenacin in mid-2017 with the goal of filing an NDA by the end of 2017; revefenacin having the potential to help address an unmet medical need for patients; revefenacin representing a key contributor in Mylan's pipeline of promising respiratory products, and supporting the growth of Mylan's respiratory franchise; Mylan's belief that it is well-positioned to support the commercial success of the product; the ongoing 12-month, open-label, active comparator safety study in more than 1,050 patients, which is expected to be completed in mid-2017; Theravance Biopharma expecting to file a New Drug Application (NDA) for revefenacin with the U.S. Food and Drug Administration (FDA) by the end of 2017; the possibility that revefenacin could provide a unique benefit to patients with low PIFR; and the possibility that this LAMA could also serve as a foundation for novel handheld combination products. These statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Because such statements inherently involve risks and uncertainties, actual future results may differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to: success of clinical trials and our and our partners' ability to execute on new product opportunities; any regulatory, legal or other impediments to our ability to bring our and our partners' products to market; other risks inherent in product development; the scope, timing, and outcome of any ongoing legal proceedings, including government investigations, and the impact of any such proceedings on our or our partners' business; actions and decisions of healthcare and pharmaceutical regulators, and changes in healthcare and pharmaceutical laws and regulations, in the United States and abroad; the impact of competition; strategies by competitors or other third parties to delay or prevent product introductions; the effect of any changes in our customer and supplier relationships and customer purchasing patterns; any other changes in third-party relationships; changes in the economic and financial conditions of  the businesses of Mylan; uncertainties and matters beyond the control of management; and the other risks detailed in Mylan's filings with the Securities and Exchange Commission. Mylan undertakes no obligation to update these statements for revisions or changes after the date of this release. 3 American Lung Association. "Trends in COPD (Chronic Bronchitis and Emphysema): Morbidity and Mortality" http://www.lung.org/assets/documents/research/copd-trend-report.pdf. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/theravance-biopharma-and-mylan-report-additional-phase-3-data-for-revefenacin-td-4208-in-several-presentations-at-2017-ats-300462228.html


The mechanism of action of SPX-101 is independent of the genetic mutations that cause CF, which makes it a potential therapy for all CF patients. "The strong clinical and preclinical data presented at ATS helps support the potential of SPX-101 to safely promote airway hydration and mucociliary clearance," said John Taylor, President and CEO, Spyryx Biosciences.  "We will be thoroughly investigating the clinical potential of SPX-101 in our HOPE-1 study, a Phase 2 trial in CF patients, which we anticipate getting underway around the middle of this year." Poster # P105 A7674 "SPX-101 Is a Novel ENaC-Targeted Therapeutic for Cystic Fibrosis that Restores Mucus Transport" This study, which was also published earlier this month in the American Journal of Respiratory and Critical Care Medicine, investigates the preclinical in vitro and in vivo efficacy of SPX-101. The authors used biochemical approaches to demonstrate that SPX-101 binds specifically to ENaC, but not structurally similar proteins, inducing ENaC internalization in human bronchial epithelial cells from healthy and CF donors.  Removal of ENaC from the plasma membrane caused a significant reduction in amiloride sensitive current and increased hydration of the airway epithelial cell cultures.  When tested in vivo, SPX-101 fully corrected mucus transport in a sheep model of CF.  SPX-101 also increased mucous movement, corrected leukocyte distribution in broncho-aveolar lavage fluid, and increased survival in the βENaC transgenic mouse model of CF. The authors concluded that via this unique biological mechanism of action in removing ENaC from the cell surface, SPX-101 promotes a durable inhibition of sodium absorption resulting in increased mucus transport. "We appreciate the opportunity to share our findings with the global respiratory care community at ATS," said Timm Crowder, PhD, Senior Vice President, Technical Operations, Spyryx Biosciences and one of the authors of the paper.  "We believe our findings highlight the opportunity for a treatment pathway that extends beyond mutation specific therapies, with the potential to deliver clinically meaningful benefit to all CF patients." Poster # 114 A4736 "Safety and Pharmacokinetics of SPX-101 in Healthy Human Subjects" This study established the clinical safety and tolerability of SPX-101in healthy, non-smoking adults age 18-50 with no history of respiratory disease and with normal lung function. Each of the 32 participants received one of four doses (20 mg, 60 mg, 120 mg or 240 mg) of SPX-101 or placebo via an investigational eFlow nebulizer system (PARI Pharma, Starnberg, Germany) in a single, ascending dose design.  There were no clinically meaningful changes in lung function as measured by forced expiratory volume in one second (FEV ) in any overall dose group.  No subject had an abnormal serum potassium value at any time in the study. There were no incidences of bronchoconstriction and no serious adverse events (SAEs) observed in the study. Marginal and transient systemic exposure was evident at low levels only at the first measurement after dosing (5 minutes) and only in 4 of 6 subjects receiving the highest dose. "We believe the results shared in the preclinical studies, combined with the absence of dose-limiting adverse effects in our 28-day toxicology and Phase 1 clinical testing, provide a strong scientific rationale for the investigation of SPX-101 in a randomized controlled clinical trial of all CF patients, regardless of their CFTR mutation," said Alistair Wheeler, MD, Chief Medical Officer, Spyryx Biosciences. About Cystic Fibrosis CF is an autosomal recessive genetic disorder affecting approximately 75,000 individuals worldwide.  The disease is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein.  CF profoundly affects the lungs and respiratory tract and is characterized by dehydration of the airway surface, resulting in reduced mucus clearance, the lung's principle mechanism for maintaining a clean environment. The mucus becomes thick and sticky, progressively accumulating into obstructions that block airflow and result in recurrent colonization of the airways by viruses and bacteria.  These pathogens lead to frequent, acute lung infections, chronic inflammation, exacerbations, and impaired lung function. The long-term result of the disease is progressive, permanent tissue damage and scarring (fibrosis) in the lung.  No cure for cystic fibrosis is known, although several treatments have been approved to address the underlying cause of the disease in some patients. Despite currently available treatment, the median age of survival for CF patients is approximately 40 years of age. About Spyryx Biosciences Spyryx Biosciences is a privately held, clinical-stage biopharmaceutical company developing innovative therapeutics to address severe lung diseases. Spyryx's lead clinical candidate, SPX-101, is a novel treatment for cystic fibrosis that has successfully completed a Phase 1 study in healthy volunteers and is advancing into Phase 2 in CF patients. The product has demonstrated a robust ability to restore mucociliary clearance in animal models of the disease and has the potential to improve lung function in all CF patients independent of their CFTR mutation. The Spyryx leadership team and scientific staff have extensive experience in the development of respiratory medicines and work closely with a broad group of clinical and scientific experts in the pulmonary field. Spyryx is funded by a first tier syndicate of life science investors, including Canaan Partners, 5AM Ventures and Hatteras Venture Partners.  Further information regarding Spyryx Biosciences is available at www.spyryxbio.com. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/spyryx-biosciences-reports-positive-data-on-spx-101-at-american-thoracic-society-international-conference-300462567.html


ALK (ALKB: DC / OMX: ALK B / AKABY / AKBLF) today announced that for the first time, allergy immunotherapy is now recommended as a treatment option in the Global Initiative for Asthma (GINA) report: Global Strategy for Asthma Management and Prevention. This global strategy is a widely recognised practical resource developed to guide healthcare professionals and policy makers, and represents the latest clinical evidence and medical practice for the treatment and management of asthma. The strategy is updated annually based on review of recent scientific literature by an international panel of experts on the GINA Science Committee. The 2017 update, which includes new information regarding the use of allergy immunotherapy, has just been released and features the following addition to steps 3 and 4 of GINA's recommended stepwise treatment of asthma in adult house dust mite (HDM) sensitive patients: Consider adding SLIT (sublingual allergy immunotherapy) in adult HDM sensitive patients with allergic rhinitis who have exacerbations despite ICS (inhaled corticosteroids), provided FEV is > 70% of predicted lung function.[1] This change draws upon recently published results from ALK's Phase III clinical trial evaluating the treatment of HDM allergic asthma with the HDM SLIT-tablet, ACARIZAX® in The Journal of the American Medical Association (JAMA) [2] Henrik Jacobi, Executive Vice President of Research & Development at ALK, said: "We are extremely pleased to see the recognition of ACARIZAX® clinical evidence in the management of asthma. This confirms our long-held conviction that allergy immunotherapy has an important role to play in the treatment of allergic asthma, a belief confirmed by the unprecedented clinical development programme for ACARIZAX®, currently the only HDM SLIT-tablet indicated for use in patients with house dust mite allergic asthma that is not well controlled." House dust mite allergy and asthma often coexist. More than half of asthmatic patients have been reported to have house dust mite sensitisation. He continued: "ALK is committed to gathering further evidence to support the wider recognition of allergy immunotherapy as a treatment option for asthma, and to investigating the potential role for allergy immunotherapy in preventing the onset of asthma." Professor J. Christian Virchow, of the University of Rostock and lead author of the recently published paper in JAMA says: "This is very encouraging. I am pleased to see findings from this important trial translated into clinical guidelines. This underlines the importance of performing robust evidence based trials in allergy immunotherapy." ACARIZAX® is currently approved for the treatment in HDM allergic asthma in 12 European countries and Australia. ALK is a research-driven global pharmaceutical company focusing on allergy prevention, diagnosis and treatment. ALK is a world leader in allergy immunotherapy - a treatment of the underlying cause of allergy. The company has approximately 2,300 employees, with subsidiaries, production facilities and distributors worldwide. ALK has entered into partnership agreements with Torii, Abbott, and Seqirus to commercialise sublingual allergy immunotherapy tablets in Japan, Russia, and South-East Asia, and Australia and New Zealand, respectively. The company is headquartered in Hørsholm, Denmark, and listed on Nasdaq Copenhagen. Find more information at http://www.alk.net. House dust mites (HDM) are the most common cause of allergy in the world. HDM allergy is estimated to affect around 90 million people in Europe, North America and Japan, and more than 100 million in China. It is estimated that one in 10 adults with allergic rhinitis are poorly controlled with current standard therapies. The condition appears early in life, is present all year round and patients face an elevated risk of developing asthma and other allergies. For some of these patients, the HDM SLIT-tablet is a relevant treatment option which can improve their quality of life and potentially modify the underlying cause of their disease. ALK's HDM SLIT-tablet is a treatment for house dust mite-induced allergic rhinitis (AR) with or without conjunctivitis and allergic asthma (AA) that is not well controlled by symptomatic medication. In Europe, where it is marketed as ACARIZAX®, the product has been approved in 14 countries for the treatment of AR, 12 of which also include the HDM AA indication. It is also approved in Japan for AR, where it is licensed by ALK to Torii and marketed under the trade name MITICURE[TM] and in Australia for HDM AR and AA, where it is licensed by ALK to Seqirus. The product is also being developed for a number of other markets around the world, including China, North America and countries in Southeast Asia. Altogether, clinical development activities for the HDM SLIT-tablet have involved more than 6,000 patients worldwide. In the 12 European countries where ACARIZAX® has been approved for HDM AR and AA, ACARIZAX® is indicated in adult patients (18-65 years) diagnosed by a clinical history and by a positive test for HDM sensitisation with at least one of the following conditions: Treating physicians should refer to full summary of product characteristics before considering ACARIZAX® for treatment in patients with house dust mite allergic asthma.[3] GINA was launched in 1993 in collaboration with the National Heart, Lung, and Blood Institute, National Institutes of Health, USA, and the World Health Organization. GINA's programme is determined and its strategies for asthma care are shaped by committees made up of leading asthma experts from around the world. The GINA Scientific Committee prepares updates to their reports and guidelines each year, which are made available on the GINA Website as they are completed. The Scientific Committee has developed a sophisticated set of procedures to review the world's literature with regards to asthma management and to update the GINA documents to reflect this state-of-the-art information.


HORSHOLM, Denmark, Feb. 28, 2017 /PRNewswire/ -- ALK (ALKB: DC / OMX: ALK B / AKABY / AKBLF) today announced that for the first time, allergy immunotherapy is now recommended as a treatment option in the Global Initiative for Asthma (GINA) report: Global Strategy for Asthma Management and Prevention. This global strategy is a widely recognised practical resource developed to guide healthcare professionals and policy makers, and represents the latest clinical evidence and medical practice for the treatment and management of asthma. The strategy is updated annually based on review of recent scientific literature by an international panel of experts on the GINA Science Committee. The 2017 update, which includes new information regarding the use of allergy immunotherapy, has just been released and features the following addition to steps 3 and 4 of GINA's recommended stepwise treatment of asthma in adult house dust mite (HDM) sensitive patients: Consider adding SLIT (sublingual allergy immunotherapy) in adult HDM sensitive patients with allergic rhinitis who have exacerbations despite ICS (inhaled corticosteroids), provided FEV is > 70% of predicted lung function.[1] This change draws upon recently published results from ALK's Phase III clinical trial evaluating the treatment of HDM allergic asthma with the HDM SLIT-tablet, ACARIZAX® in The Journal of the American Medical Association (JAMA) [2] Henrik Jacobi, Executive Vice President of Research & Development at ALK, said: "We are extremely pleased to see the recognition of ACARIZAX® clinical evidence in the management of asthma. This confirms our long-held conviction that allergy immunotherapy has an important role to play in the treatment of allergic asthma, a belief confirmed by the unprecedented clinical development programme for ACARIZAX®, currently the only HDM SLIT-tablet indicated for use in patients with house dust mite allergic asthma that is not well controlled." House dust mite allergy and asthma often coexist. More than half of asthmatic patients have been reported to have house dust mite sensitisation. He continued: "ALK is committed to gathering further evidence to support the wider recognition of allergy immunotherapy as a treatment option for asthma, and to investigating the potential role for allergy immunotherapy in preventing the onset of asthma." Professor J. Christian Virchow, of the University of Rostock and lead author of the recently published paper in JAMA says: "This is very encouraging. I am pleased to see findings from this important trial translated into clinical guidelines. This underlines the importance of performing robust evidence based trials in allergy immunotherapy." ACARIZAX® is currently approved for the treatment in HDM allergic asthma in 12 European countries and Australia. ALK is a research-driven global pharmaceutical company focusing on allergy prevention, diagnosis and treatment. ALK is a world leader in allergy immunotherapy - a treatment of the underlying cause of allergy. The company has approximately 2,300 employees, with subsidiaries, production facilities and distributors worldwide. ALK has entered into partnership agreements with Torii, Abbott, and Seqirus to commercialise sublingual allergy immunotherapy tablets in Japan, Russia, and South-East Asia, and Australia and New Zealand, respectively. The company is headquartered in Hørsholm, Denmark, and listed on Nasdaq Copenhagen. Find more information at http://www.alk.net. House dust mites (HDM) are the most common cause of allergy in the world. HDM allergy is estimated to affect around 90 million people in Europe, North America and Japan, and more than 100 million in China. It is estimated that one in 10 adults with allergic rhinitis are poorly controlled with current standard therapies. The condition appears early in life, is present all year round and patients face an elevated risk of developing asthma and other allergies. For some of these patients, the HDM SLIT-tablet is a relevant treatment option which can improve their quality of life and potentially modify the underlying cause of their disease. ALK's HDM SLIT-tablet is a treatment for house dust mite-induced allergic rhinitis (AR) with or without conjunctivitis and allergic asthma (AA) that is not well controlled by symptomatic medication. In Europe, where it is marketed as ACARIZAX®, the product has been approved in 14 countries for the treatment of AR, 12 of which also include the HDM AA indication. It is also approved in Japan for AR, where it is licensed by ALK to Torii and marketed under the trade name MITICURE[TM] and in Australia for HDM AR and AA, where it is licensed by ALK to Seqirus. The product is also being developed for a number of other markets around the world, including China, North America and countries in Southeast Asia. Altogether, clinical development activities for the HDM SLIT-tablet have involved more than 6,000 patients worldwide. In the 12 European countries where ACARIZAX® has been approved for HDM AR and AA, ACARIZAX® is indicated in adult patients (18-65 years) diagnosed by a clinical history and by a positive test for HDM sensitisation with at least one of the following conditions: Treating physicians should refer to full summary of product characteristics before considering ACARIZAX® for treatment in patients with house dust mite allergic asthma.[3] GINA was launched in 1993 in collaboration with the National Heart, Lung, and Blood Institute, National Institutes of Health, USA, and the World Health Organization. GINA's programme is determined and its strategies for asthma care are shaped by committees made up of leading asthma experts from around the world. The GINA Scientific Committee prepares updates to their reports and guidelines each year, which are made available on the GINA Website as they are completed. The Scientific Committee has developed a sophisticated set of procedures to review the world's literature with regards to asthma management and to update the GINA documents to reflect this state-of-the-art information.


LONDON & BRISBANE, Calif.--(BUSINESS WIRE)--GlaxoSmithKline plc (LSE/NYSE: GSK) and Innoviva, Inc. (NASDAQ: INVA) today announced positive headline results from a non-inferiority lung function study, which demonstrated that patients with well-controlled asthma were able to switch to the once-daily Relvar® Ellipta® (fluticasone furoate/vilanterol, FF/VI) 100/25, an inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) combination, from the twice-daily Seretide® Accuhaler® (fluticasone propionate /salmeterol, FP/SAL) 250/50, without compromising their lung function. Patients randomised to FF/VI taken once-daily maintained a lung function comparable with those randomised to the twice-daily FP/SAL [difference +19mL (95% CI: -11mL, +49mL], meeting the study’s primary endpoint, based on the lower bound (-11ml) of the 95% confidence interval falling above the non-inferiority margin of -100mL. A third treatment arm with fluticasone propionate (FP), ICS monotherapy, was included to detect a lung function difference between treatments. Results demonstrated statistically significant differences in favour of the ICS/LABA combinations to FP (p<0.001). The incidences of on-treatment serious adverse events (SAEs) and adverse events (AEs) of special interest were consistent with the known safety profile of FF/VI, established in asthma patients from other studies. Eric Dube, SVP and Global Head of Respiratory Franchise, GSK said: “At GSK we are constantly searching for ways in which we can help patients better manage their asthma. In this positive study we have demonstrated non-inferiority for once-daily Relvar versus twice-daily Seretide on lung function. This gives us confidence that for patients who struggle taking a twice-daily treatment regimen, there may be a once-daily treatment option available, providing greater physician choice to help patients.” Mike Aguiar, CEO of Innoviva, Inc., added: “We believe the results of this study are important for patients and physicians. They provide additional evidence that patients with persistent asthma, who are currently treated with a twice-daily ICS/LABA, in this case Seretide, can experience a similar level of benefit in lung function when treated with Relvar Ellipta, which only needs to be taken once a day.” The study design was agreed with European regulatory authorities. GSK now intends to submit this data to the European Medicines Agency (EMA). Results from the study will be shared in future publications and presentations. Following a 4-week open-label treatment period with FP/SAL 250/50 twice-daily, patients with well controlled asthma were randomised to receive either FF/VI 100/25 once-daily, FP/SAL 250/50 twice-daily or FP 250 twice-daily in a double-blind, double-dummy manner for 24 weeks at multiple centres in 12 countries. The primary objective of the study was to demonstrate non-inferiority of Relvar Ellipta 100/25 once-daily with Seretide Accuhaler 250/50 twice-daily in adult and adolescent subjects 12 years of age and older with persistent bronchial asthma, well controlled on twice-daily ICS/LABA. The endpoint for the study was the change from baseline in clinic visit evening FEV (pre-brochodilator and pre-dose) at the end of the 24-week treatment period. To demonstrate the non inferiority of FF/VI vs FP/SAL the lower limit of the 95% confidence interval for the mean difference in change from baseline for evening FEV needed to be greater than the pre defined margin of -100mL. This was to rule out the possibility that FF/VI was more than -100mL inferior to FP/SAL. Asthma is a chronic lung disease that inflames and narrows the airways. Asthma affects 358 million people worldwide. Despite medical advances, more than half of patients continue to experience poor control and significant symptoms impacting their daily life. The causes of asthma are not completely understood but likely involve an interaction between a person’s genetic make-up and the environment. Key risk factors are inhaled substances that provoke allergic reactions or irritate the airways. Relvar Ellipta is a once-daily dual combination treatment comprising fluticasone furoate, an inhaled corticosteroid and vilanterol, a long-acting beta -agonist, in a single inhaler, the Ellipta®. Relvar Ellipta is indicated in Europe in the regular treatment of patients aged 12 and over with asthma, where use of a combination product (long-acting ß2–agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and 'as-needed' short-acting ß -agonist (SABA). Full EU prescribing information is available at: EU Prescribing Information for Relvar Ellipta. FF/VI is contraindicated in patients with hypersensitivity to either fluticasone furoate, vilanterol, or any of the excipients. FF/VI should not be used to treat acute asthma symptoms or an acute exacerbation in COPD, for which a short-acting bronchodilator is required. Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control and patients should be reviewed by a physician. Patients should not stop therapy with FF/VI in asthma or COPD, without physician supervision since symptoms may recur after discontinuation. Asthma-related adverse events and exacerbations may occur during treatment with FF/VI. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of treatment with FF/VI. Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a short-acting inhaled bronchodilator. FF/VI should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary. Cardiovascular effects, such as cardiac arrhythmias e.g. supraventricular tachycardia and extrasystoles may be seen with sympathomimetic medicinal products including FF/VI. Therefore fluticasone furoate/vilanterol should be used with caution in patients with severe cardiovascular disease. For patients with moderate to severe hepatic impairment, the 92/22 mcg dose should be used and patients should be monitored for systemic corticosteroid-related adverse reactions. FF/VI 184/22 mcg is not indicated for patients with COPD. There is no additional benefit of the 184/22 mcg dose compared to the 92/22 mcg dose and there is a potential increased risk of pneumonia and systemic corticosteroid-related adverse reactions. An increase in the incidence of pneumonia has been observed in subjects with COPD receiving FF/VI. There was also an increased incidence of pneumonias resulting in hospitalisation. In some instances these pneumonia events were fatal. The incidence of pneumonia in patients with asthma was common at the higher dose. In a previous study of FF/VI in asthma the incidence of pneumonia in patients with asthma taking FF/VI 184/22 mcg was numerically higher compared with those receiving FF/VI 92/22 mcg or placebo. Hyperglycaemia: There have been reports of increases in blood glucose levels in diabetic patients and this should be considered when prescribing to patients with a history of diabetes mellitus. Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). FF/VI should be administered with caution in patients with pulmonary tuberculosis or in patients with chronic or untreated infections. Data from large asthma and COPD clinical trials were used to determine the frequency of adverse reactions associated with FF/VI. Very common adverse reactions (occurring in >1/10 patients) with FF/VI were headache and nasopharyngitis. Common adverse reactions (occurring in >1/100 to <1/10 patients) were pneumonia, upper respiratory tract infection, bronchitis, influenza, candidiasis of mouth and throat, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain, fractures, and pyrexia and muscle spasms..Extrasystoles were observed as an uncommon adverse reaction (occurring in >1/1,000 to <1/100 patients). Rare adverse reactions (occurring in >1/10,000 to < 1/1,000) were hypersensitivity reactions (including anaphylaxis, angioedema, rash and urticaria), anxiety, tremor, palpitations, tachycardia and paradoxical bronchospasm. With the exception of pneumonia and fractures, the safety profile was similar in patients with asthma and COPD. During clinical studies, pneumonia and fractures were more frequently observed in patients with COPD. Relvar Ellipta is known as Breo Ellipta in the United States. Breo Ellipta is licensed in the US for: Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in Breo Ellipta, increase the risk of asthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, physicians should only prescribe Breo Ellipta for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue Breo Ellipta) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use BREO ELLIPTA for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids. Full US prescribing information, including BOXED WARNING and Medication Guide is available at us.gsk.com or US Prescribing Information for Breo Ellipta. Seretide Accuhaler is a twice-daily dual combination treatment comprising fluticasone propionate /salmeterol, in the Accuhaler inhaler. Seretide Accuhaler is indicated in Europe in the regular treatment of patients aged 4 and over with asthma, where use of a combination product (long-acting ß2–agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and 'as-needed' short-acting ß -agonist (SABA); Patients already adequately controlled on both ICS and LABA. For the UK Summary of Product Characteristics (SmPC), please visit: https://www.medicines.org.uk/emc/medicine/2317/SPC/Seretide+100,+250,+500+Accuhaler Uses: Asthma: Regular treatment of asthma, where a long-acting β agonist and inhaled corticosteroid is appropriate, i.e. patients uncontrolled on inhaled corticosteroids and 'as needed' short-acting inhaled bronchodilator or patients controlled on inhaled corticosteroid and long-acting β agonist. Lowest strength Seretide (salmeterol 25mcg/fluticasone propionate 50 mcg and salmeterol 50mcg/fluticasone propionate 100 mcg) not appropriate in severe asthma. COPD: Symptomatic treatment of patients with COPD with a FEV1 <60% predicted normal (pre-bronchodilator) and a history of repeated exacerbations, who have significant symptoms despite regular bronchodilator therapy. Dosage and administration: Inhalation only. Asthma: Adults and adolescents 12 years and over: Seretide Accuhaler - one inhalation b.d. of: Seretide 100 (salmeterol 50 mcg/fluticasone propionate 100 mcg) or Seretide 250 (salmeterol 50 mcg/fluticasone propionate 250 mcg) or Seretide 500 (salmeterol 50 mcg/fluticasone propionate 500 mcg), Seretide Evohaler – two puffs b.d. of: Seretide 50 (salmeterol 25 mcg/fluticasone propionate 50 mcg) or Seretide 125 (salmeterol 25 mcg/fluticasone propionate 125mcg) or Seretide 250 (salmeterol 25 mcg/fluticasone propionate 250 mcg). Children 4-11 years: Seretide 50 Evohaler (salmeterol 25 mcg/fluticasone propionate 50 mcg): two puffs b.d. Spacer recommended for co-ordination. Seretide 100 Accuhaler (salmeterol 50 mcg/fluticasone propionate 100 mcg) one inhalation b.d. Regularly review patients and reduce dose to lowest that maintains effective symptom control. Where the control of symptoms is maintained with the lowest strength of the combination, patients may be prescribed an inhaled corticosteroid alone, or if a long-acting β agonist is required, Seretide may be given once daily. If rapid control of asthma in adults or adolescents with moderate persistent asthma (defined as patients with daily symptoms, daily rescue use and moderate to severe airflow limitation) is essential, an initial dose of two inhalations b.d. of Seretide 50 Evohaler (salmeterol 25 mcg/fluticasone propionate 50 mcg) or one inhalation b.d. of Seretide 100 Accuhaler (salmeterol 50 mcg/fluticasone propionate 100 mcg) may be considered on a short-term basis. Once control of asthma is attained treatment should be regularly reviewed and stepped down. Doubling the dose of all strengths of Seretide may be considered when adult patients require additional short-term (up to 14 days) inhaled corticosteroid therapy but this causes a small increase in β-agonist-related adverse events. COPD: one inhalation b.d. of Seretide 500 Accuhaler (salmeterol 50mcg/fluticasone propionate 500 mcg). Contraindications: Hypersensitivity to the active ingredients or to any of the excipients. Precautions: Pulmonary tuberculosis, fungal, viral or other infections of the airway, severe cardiovascular disorders, heart rhythm abnormalities, diabetes mellitus, hypokalaemia and thyrotoxicosis. Increased reporting of pneumonia and bronchitis in patients with COPD receiving Seretide compared with placebo. If a patient with severe COPD has experienced pneumonia, treatment with Seretide should be re-evaluated. Paradoxical bronchospasm post dose. Severe unstable asthma: Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases. Consider increased inhaled/additional corticosteroid therapy. Acute symptoms: Not for acute symptoms. Use short-acting inhaled bronchodilator. Systemic effects: Systemic effects of inhaled corticosteroids may occur, particularly at high doses for prolonged periods, but much less likely than with oral corticosteroids. May include Cushing’s syndrome, cushingoid features, adrenal suppression, adrenal crisis, growth retardation in children and adolescents, decrease in bone mineral density, cataract, glaucoma and, more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Monitor height of children on prolonged inhaled corticosteroid therapy. Tremor, palpitations and headache, have been reported with β agonist treatment. In asthma, therapy should be down titrated under physician supervision to lowest effective dose and treatment should not be abruptly stopped due to risk of exacerbation. Serious asthma-related adverse events and exacerbations may occur during treatment with Seretide. Patients should not be initiated on Seretide during an exacerbation, or if they have significantly worsening or acutely deteriorating asthma. Data from a large asthma trial suggested patients of black African or Afro-Caribbean ancestry were at increased risk of serious respiratory-related events or deaths when using salmeterol. All patients should continue treatment but seek medical advice if asthma symptoms remain uncontrolled or worsen when initiated on Seretide or using Seretide. In COPD cessation of therapy may also be associated with decompensation and should be supervised by a physician. Transfer from oral steroids: Special care needed. Consider appropriate steroid therapy in stressful situations. Drug interactions: Avoid beta-blockers. Avoid concomitant administration of ketoconazole or other potent (e.g. itraconazole, telithromycin, ritonavir) and moderate (erythromycin) CYP3A4 inhibitors unless benefits outweigh potential risk. β adrenergic blockers may weaken or antagonise the effect of salmeterol. Potentially serious hypokalaemia may result from β agonist therapy. Particular caution is advised in acute severe asthma as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics. Side effects: Very Common: headache, nasopharyngitis. Common: candidiasis of the mouth and throat, hoarseness/dysphonia, throat irritation, pneumonia, bronchitis, hypokalaemia, sinusitis, contusions, traumatic fractures, arthralgia, myalgia, muscle cramps. Uncommon: respiratory symptoms (dyspnoea), anxiety, tremor, palpitations, tachycardia, angina pectoris, atrial fibrillation, cutaneous hypersensitivity reactions, hyperglycaemia, sleep disorders, cataract. Rare: angioedema, respiratory symptoms (bronchospasm), anaphylactic reactions including anaphylactic shock, Cushings syndrome, cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, oesophageal candidiasis, behavioural changes including psychomotor hyperactivity and irritability (predominately in children), glaucoma, cardiac arrhythmias and paradoxical bronchospasm. Not known: depression or aggression (particularly in children). Paradoxical bronchospasm: substitute alternative therapy. Seretide Accuhaler is known as ADVAIR DISKUS in the United States. ADVAIR DISKUS is licensed in the US for: Long-acting beta2-adrenergic agonists (LABA), such as salmeterol, one of the active ingredients in ADVAIR DISKUS, increase the risk of asthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, physicians should only prescribe ADVAIR DISKUS for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue ADVAIR DISKUS) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use ADVAIR DISKUS for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids. Full US prescribing information, including BOXED WARNING and Medication Guide is available at us.gsk.com or US Prescribing Information for Advair Diskus. GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com. RELVAR®, BREO®, ELLIPTA®, SERETIDE®, ACCUHALER®, ADVAIR®, DISKUS® are trademarks of the GlaxoSmithKline group of companies. Innoviva – Innoviva is focused on bringing compelling new medicines to patients in areas of unmet need by leveraging its significant expertise in the development, commercialization and financial management of bio-pharmaceuticals. Innoviva's portfolio is anchored by the respiratory assets partnered with Glaxo Group Limited (GSK), including RELVAR®/BREO® ELLIPTA® and ANORO® ELLIPTA®, which were jointly developed by Innoviva and GSK. Under the agreement with GSK, Innoviva is eligible to receive associated royalty revenues from RELVAR®/BREO® ELLIPTA®, ANORO® ELLIPTA®. In addition, Innoviva retains a 15 percent economic interest in future payments made by GSK for earlier-stage programs partnered with Theravance Biopharma, Inc., including the closed triple combination therapy for COPD. For more information, please visit Innoviva's website at www.inva.com. GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Risk factors' in the company's Annual Report on Form 20-F for 2015. This press release contains certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives and future events, including the development, regulatory and commercial plans for closed triple combination therapy and the potential benefits and mechanisms of action of closed triple combination therapy. Innoviva intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks, uncertainties and assumptions. These statements are based on the current estimates and assumptions of the management of Innoviva as of the date of this press release and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Innoviva to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are described under the headings "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" contained in Innoviva's Annual Report on Form 10-K for the year ended December 31, 2015 and Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, which are on file with the U.S. Securities and Exchange Commission (SEC) and available on the SEC's website at www.sec.gov. Additional factors may be described in those sections of Innoviva's Annual Report on Form 10-K for the year ended December 31, 2016, to be filed with the SEC in the first quarter of 2017.. In addition to the risks described above and in Innoviva's other filings with the SEC, other unknown or unpredictable factors also could affect Innoviva's results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. The information in this press release is provided only as of the date hereof, and Innoviva assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law. (INVA-G).


BOULDER, Colo., Feb. 23, 2017 (GLOBE NEWSWIRE) -- Nivalis Therapeutics, Inc. (NASDAQ:NVLS), a pharmaceutical company historically focused on developing innovative solutions for people with cystic fibrosis (CF), today announced topline results from the Company's Phase 2 trial evaluating the efficacy and safety of cavosonstat at a dose of 400 mg in adult patients with CF who had one copy of the F508del-CFTR mutation and a second gating mutation, and were being treated with Kalydeco™ (ivacaftor). There were no dose limiting toxicities and cavosonstat was well tolerated in the trial. Cavosonstat, when added to Kalydeco therapy, did not demonstrate benefit in absolute change in percent predicted FEV the trial’s primary endpoint, or in sweat chloride reduction at 8 weeks. Summary of Key Data The data announced today are from a Phase 2, double-blind, randomized, placebo controlled, trial that evaluated the efficacy and safety of one dose of cavosonstat administered twice daily (BID) in adult patients with CF who were heterozygous for the F508del-CFTR mutation and a gating mutation, being treated with Kalydeco. The 12-week trial included a total of 19 adults who received treatment with cavosonstat (400 mg) added to Kalydeco (n=15) or with placebo added to Kalydeco (n=4). The trial included a 4-week withdrawal and follow-up period once patients had completed 8 weeks of dosing. The primary endpoint of the trial was change in absolute percent predicted FEV from baseline to week 8. These primary and key secondary endpoints are shown in the table below. The increase in body mass index (BMI) reflecting a gain in weight in this study was similar to increases in BMI observed in two prior studies of cavosonstat in CF patients homozygous for F508del-CFTR. In one study, cavosonstat was administered over 4 weeks to CF patients who were not being treated with OrkambiTM and in the other study cavosonstat was administered over 12 weeks to patients who were being treated with Orkambi. End of treatment BMI data from these studies are summarized in the table below. These data suggest that GSNOR inhibition may have improved the nutritional status of patients with CF in these studies. “We are sincerely grateful to those who participated in this trial, including the patients, their families, the trial investigators and our employees,” said Steven Shoemaker, M.D., Medical Director at Nivalis. “We hope that the data from this trial will help inform the overall body of CF research, and help others in the design of future CF trials.” About Nivalis Therapeutics, Inc. Nivalis Therapeutics, Inc. (http://www.nivalis.com) is a pharmaceutical company that has historically been focused on the discovery and development of product candidates for patients with cystic fibrosis, or CF. Our GSNOR inhibitors selectively target an enzyme known as S-nitrosoglutathione reductase, which we refer to as GSNOR. GSNOR regulates levels of an endogenous protein known as S-nitrosoglutathione, or GSNO.  Depleted levels of GSNO have been associated with CF, asthma, inflammatory bowel diseases and certain cardiovascular diseases. However, in light of recent disappointing results of a Phase 2 clinical trial of our lead product candidate, cavosonstat, in CF, we determined to not pursue the development of this compound in CF and to wind down our research and development activities as we shift our strategic emphasis to investigating and evaluating strategic alternatives. About Cavosonstat Cavosonstat works through a novel mechanism of action called GSNOR inhibition. Nivalis discovered and owns exclusive rights to cavosonstat in the United States (U.S.) and all other major markets, including U.S. composition of matter patent protection until at least 2031. Cavosonstat was granted Orphan Drug and Fast Track designations in CF by the FDA in 2016. Nivalis has completed clinical studies with cavosonstat, including two Phase 1a dose-escalation safety studies in healthy volunteers, a Phase 1b safety study and a Phase 2 trial in adult patients with CF who had two copies of the F508del-CFTR mutation and in the Phase 2 trial were being treated with Orkambi and a second Phase 2 trial of cavosonstat in patients with CF who had one copy of the F508del-CFTR mutation and a second gating mutation, and were being treated with Kalydeco. Forward Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements related to the potential for GSNOR inhibitors to improve nutritional status in CF. These forward-looking statements are based on the current intent and expectations of the management of the Company. These statements are not guarantees of future performance or actions and involve risks and uncertainties that are difficult to predict. The Company’s actual performance in the timing and outcome of actions and events may differ materially from those expressed or implied in the forward-looking statements because such statements are based on assumptions and projections relating to these activities that are inherently uncertain and may also be affected by risks such as: that certain clinical data from prior trials may not be predictive of results achieved in other trials of a drug candidate relating to the same or different indications; and the other risks and uncertainties described in the Company’s SEC reports filed under the Securities Exchange Act of 1934, including its most recent annual report on Form 10-K filed with the Securities and Exchange Commission on February 13, 2017. All information in this press release is as of the date of this release, and Nivalis undertakes no duty to update or revise this information unless required by law.

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