News Article | May 20, 2017
Chiesi Group (Chiesi), an international research-focused healthcare company, announced today that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending marketing authorization for the extrafine triple combination ICS/LABA/LAMA, under the brand name Trimbow®, for the first time in a single inhaler for the treatment of Chronic Obstructive Pulmonary Disease (COPD). Trimbow is a combination of Inhaled Corticosteroid (ICS) / Long-acting β2-agonist (LABA) / long-acting muscarinic antagonist (LAMA) that contains Beclometasone dipropionate (BDP), Formoterol fumarate (FF) and Glycopyrronium bromide (GB). Paolo Chiesi, Chiesi Group Vice President and Head of R&D, said, "Today's positive opinion is an important step forward to make our extrafine Triple combination available to COPD patients. COPD affects millions of people across Europe, and Chiesi is committed to developing new therapeutic options that could help these patients' adherence to the therapy, thus reducing the risk of exacerbations and improving their quality of life. With this goal in mind, Chiesi has also developed the first fixed dose ICS/LABA/LAMA Triple combination." Patients with COPD have unmet therapeutic needs, such as reducing the risk of exacerbations that impair the quality of life, which may lead to hospitalization or even be life-threatening 3-6. Indeed, the quality of life7 worsens when symptoms, such as dyspnoea and cough, are not controlled, and the patient needs to be hospitalized. Moreover, COPD is a disease that deteriorates with time8 and therapy often needs to be progressively intensified. This requires patients to be treated with many drugs that, to date, have to be taken through two or even three inhalers. The possibility of taking all drugs needed, and reaching both central and peripheral airways through only one inhaler considerably simplifies the treatment of COPD patients, decreasing the burden on patients and, thus, improving adherence.9,10 Therefore, a simplified treatment option based on ICS/LABA/LAMA that is able to improve lung function and reduce the risk of exacerbations in COPD patients, uncontrolled by previous therapies, would definitely satisfy those unmet needs. The CHMP recommendation is based on the efficacy and safety data of 12 clinical studies involving more than 7,000 patients. Two of the studies were recently published by The Lancet -- one of the most prestigious international medical journals: The CHMP positive opinion is one of the final steps before the European Commission grants marketing authorization. A final decision by the European Commission and official grant of the marketing authorization is expected during the third quarter of 2017. COPD is a respiratory disease characterized by a persistent bronchial obstruction, associated with an increased chronic inflammatory response of the airways to noxious particles or gas. The classic symptoms associated with COPD are dyspnoea, chronic cough and chronic productive sputum. In some cases, an acute worsening of the above-mentioned symptoms may occur, triggering an exacerbation. A double mechanism is at work in the bronchial obstruction in COPD patients: on one hand, an inflammation of the small airways together with the thickening of the airways walls and increased airflow resistance may occur. On the other, a progressive destruction of lung parenchyma (emphysema) associated with the loss of elastic retraction of the lung may take place. It is important to underline that both mechanisms may coexist, leading to a significant airflow reduction throughout the lungs. Trimbow is the first extrafine fixed triple combination of Inhaled Corticosteroid (ICS) / Long-acting β2-agonist (LABA) / long-acting muscarinic antagonist (LAMA) that contains Beclometasone dipropionate (BDP), Formoterol fumarate (FF) and Glycopyrronium bromide (GB) Trimbow will be available as twice a day pMDI (pressurized metered dose inhaler) to be licensed for COPD indication, with an approved indication for maintenance treatment of COPD patients. Based in Parma, Italy, Chiesi Farmaceutici is an international research-focused Healthcare Group, with over 80 years of experience in the pharmaceutical industry, present in 26 countries. Chiesi researches, develops and markets innovative drugs in the respiratory therapeutics, specialist medicine and rare disease areas. Its R&D organization is headquartered in Parma (Italy), and integrated with 6 other key R&D groups in France, the USA, the UK, Sweden and Denmark to advance Chiesi's pre-clinical, clinical and registration programmes. Chiesi employs nearly 5,000 people. For more information please visit www.chiesi.com. 1 Singh D, Papi A, Corradi M, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, and Vestbo J. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2 agonist for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Accepted (2016) THELANCET-D-16-04974R1;S0140-6736(16)31354-X. 2 Vestbo J, Papi A, Corradi M, Blazhko V, Montagna I, Francisco C, et al. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial. www.thelancet.com Published online April 3, 2017 http://dx.doi.org/10.1016/S0140-6736(17)30567-6. 3 Celli BR et al., An official American Thoracic Society/European Respiratory Society statement: research questions in COPD. Eur Respir J. 2015;45:879-905. 6 Groenewegen KH, Schols AM, Wouters EF. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD. Chest. 2003;124:459-67. 7 Hernandez P, Balter M, Bourbeau J, Hodder R. Living with chronic obstructive pulmonary disease: A survey of patients' knowledge and attitudes. Respiratory Medicine. 2009;103:1004-12. 8 Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, Progetto Mondiale BPCO, aggiornamento 2016 (www.goldcopd.org). 9 Stoloff SW, Stempel DA, Meyer J, et al. Improved refill persistence with fluticasone propionate and salmeterol in a single inhaler compared with other controller therapies. J Allergy Clin Immunol. 2004;113:245-51. 10 Nelson HS. Combination therapy of long-acting beta agonists and inhaled corticosteroids in the management of chronic asthma. Curr Allergy Asthma Rep. 2005;5:123-9.
News Article | May 22, 2017
WILMINGTON, Del.--(BUSINESS WIRE)--Results from the Phase III ZONDA trial presented at the American Thoracic Society (ATS) 2017 International Congress demonstrated that adding benralizumab to standard of care allowed patients dependent on OCS to significantly reduce or discontinue steroids while maintaining asthma control. Detailed results of the ZONDA study were published today in the New England Journal of Medicine. The trial achieved its primary efficacy endpoint, demonstrating statistically-significant and clinically relevant reduction in daily maintenance OCS use with two benralizumab dosing regimens compared with placebo. Patients treated with benralizumab were more than four times as likely to reduce their OCS dose than those in the placebo group. The median reduction in OCS dose was 75% for patients treated with benralizumab versus 25% with placebo. The ZONDA trial demonstrated significant outcomes for secondary endpoints. For OCS reduction in the 8-week dosing regimen: Analysis of prevention or reduction of acute asthma events in benralizumab-treated patients on the 8-week dosing regimen demonstrated: Dr. Parameswaran Nair, Professor of Respiratory Medicine at McMaster University in Hamilton, Canada and the lead investigator of the trial, said: “Benralizumab showed an impressive clinical efficacy by reducing exacerbations rate by up to 70% at the same time enabling patients with severe asthma to significantly lower their prednisone dose and maintain their lung function. This is likely due to its unique mechanism of action of inhibiting the receptor for interleukin-5 and potentially depleting blood and airway eosinophils.” Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: “One of the known clinical characteristics of the eosinophilic asthma phenotype is an over reliance on oral steroids to manage severe uncontrolled disease. What is exciting about the ZONDA trial is that we have shown benralizumab delivers a clinically meaningful OCS reduction alongside a substantial reduction in asthma exacerbation rate including emergency treatment or hospitalizations in this difficult-to-treat patient population.” The ZONDA trial evaluated the effect of benralizumab 30 mg administered subcutaneously (SC) using either an 8- or 4-week dosing regimen for 28 weeks in adult patients with severe, uncontrolled eosinophilic asthma receiving high-dose inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) and OCS with or without additional asthma controllers. Benralizumab was well-tolerated, with an overall adverse event profile like that of placebo and that observed in previous Phase III trials. The most common adverse events (≥10%) in benralizumab-treated patients observed in ZONDA were nasopharyngitis, worsening asthma and bronchitis. The data from the ZONDA trial, along with the pivotal Phase III SIROCCO and CALIMA trials, were included in regulatory submissions for benralizumab. Benralizumab is not approved anywhere in the world, but is under regulatory review in the US, EU, Japan and several other countries with a US PDUFA date in the fourth quarter of 2017. Asthma affects 315 million individuals worldwide, and up to 10% of asthma patients have severe asthma which may be uncontrolled despite high doses of standard of care asthma controller medicines and can require the use of chronic oral corticosteroids (OCS). Severe uncontrolled asthma is debilitating and potentially fatal with patients experiencing frequent exacerbations and significant limitations on lung function and quality of life. Severe, uncontrolled asthma has an eight times higher risk of mortality than severe asthma. Uncontrolled asthma can lead to a dependence on OCS, with systemic steroid exposure potentially leading to serious and irreversible short- and long-term adverse effects, including weight gain, diabetes, osteoporosis, glaucoma, anxiety, depression, cardiovascular disease and immunosuppression. There is also a significant physical and socio-economic burden of severe asthma with these patients accounting for 50% of asthma-related costs. ZONDA was a 28-week, randomized, double-blind, parallel-group, placebo-controlled, multicenter Phase III trial which included 220 adult patients with severe, uncontrolled asthma requiring treatment with high-dose ICS plus a LABA and chronic OCSs and blood eosinophil counts of at least 150 cells/μL1. The trial assessed the effects of benralizumab (30 mg every 4 weeks or every 8 weeks; first three doses every 4 weeks) versus placebo on OCS dose reduction while maintaining asthma control for adult patients with severe asthma. The primary endpoint was the percentage change in OCS dose from baseline to week 28. Patients underwent randomization at week 0 to receive benralizumab or placebo, and entered the 4-week induction phase, during which optimized OCS doses were maintained. In the subsequent reduction phase (weeks 4–24), OCS doses were reduced by 2.5–5.0 mg/d at 4-weekly intervals. Only patients with optimized baseline OCS doses ≤12.5 mg/d were eligible for 100% dose reduction. See the New England Journal of Medicine manuscript for additional information on OCS dose protocol in the trial. Benralizumab is an anti-eosinophil monoclonal antibody that induces direct, and near-complete depletion of eosinophils via antibody dependent cell-mediated cytotoxicity (ADCC). Depletion of circulating eosinophils is rapid, with an onset of action within 24 hours as confirmed in early phase I/II trials. In the pivotal Phase III trials, SIROCCO and CALIMA, benralizumab demonstrated significant reduction in exacerbations and improved lung function and asthma symptoms in severe, uncontrolled eosinophilic asthma patients. Eosinophils are the biological effector cells that drive inflammation and airway hyper-responsiveness in approximately 50% of asthma patients, leading to frequent exacerbations, impaired lung function and asthma symptoms. Benralizumab is not approved anywhere in the world, but is under regulatory review in the US, EU, Japan and several other countries. Benralizumab was developed by MedImmune, AstraZeneca’s global biologics research and development arm and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Hakko Kirin Co., Ltd. Respiratory disease is one of AstraZeneca’s main therapy areas, and the Company has a growing portfolio of medicines that reached more than 18 million patients in 2016. AstraZeneca’s aim is to transform asthma and COPD treatment through inhaled combinations at the core of care, biologics for the unmet needs of specific patient populations, and scientific advancements in disease modification. The Company is building on a 40-year heritage in respiratory disease and AstraZeneca’s capability in inhalation technology spans both pMDIs and dry powder inhalers, as well as the innovative Co-SuspensionTM Delivery Technology. The company’s biologics include benralizumab (anti-eosinophil, anti-IL-5rɑ), which has been accepted for regulatory review in the US, EU and Japan, tralokinumab (anti-IL-13), which is currently in Phase III, and tezepelumab (anti-TSLP), which successfully achieved its Phase IIb primary endpoint. AstraZeneca’s research is focused on addressing underlying disease drivers focusing on the lung epithelium, lung immunity and lung regeneration. AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of Autoimmunity, Neuroscience and Infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
News Article | May 23, 2017
A study by researchers at the University of Tartu found that exposure to traffic-related particulate matter (PM) could be associated with cardiac diseases among people in the city of Tartu, Estonia, whereas PM from residential heating did not. Results of the study adds valuable information to the current knowledge as it they confirms the link between health effects and low-level PM, and association is different depending on the PM source. Results were published in the September 2016 edition of the journal The Open Respiratory Medicine Journal. Residential heating and traffic are two main sources of particulate matter (PM) in Northern European cities. Due to insufficient air flow and low combustion temperatures, several pollutants are produced from a log burning in residential wood stoves, like organic carbon, soot, polycyclic aromatic hydrocarbons (PAHs) etc. Air pollution from traffic includes exhaust particles, nitrogen oxides, black smoke,road dust from road abrasion and tire and brake wear and other pollutants. Short- and long-term exposure to fine (PM2.5) and coarse particles (PM2.5-10) are associated with cardiovascular and respiratory morbidity or mortality. Few studies have analyzed health effects differences from traffic and residential heating. Self-reported health data from RHINE III (Respiratory Health in Northern Europe) study was used and it was linked to the 2012 annual and 2009?2012 average mean local heating induced PM2.5, traffic induced PM10, and all sources PM2.5 modelled concentrations inthe city of Tartu, Estonia. "We found that traffic induced PM compared to residential heating induced PM associated more strongly with cardiac diseases.No significant associations were found with respiratory symptoms. PM modelling results show that traffic induced PM had higher concentration in the city of Tartu compared residential induced PM. Health effects were found in PM concentrations below limit values set by Estonian and EU legislation," said Mihkel Pindus, MSc, lead author of the study and PhD student with the University of Tartu. This study was financed by grants IUT20-11 and IUT34-17 from The Estonian Ministry of Education and Research, and grant ETF8523 from The Estonian Science Foundation.
News Article | May 5, 2017
LONDON--(BUSINESS WIRE)--GlaxoSmithKline plc (LSE/NYSE: GSK) and Innoviva Inc (NASDAQ: INVA) today announced positive results from the innovative Salford Lung Study (SLS) in asthma, carried out amongst 4,233 patients treated by their own General Practitioner in everyday clinical practice. This open-label, randomised study showed that significantly more asthma patients initiated on treatment with Relvar Ellipta 100/25mcg or 200/25mcg (fluticasone furoate ‘FF’/vilanterol ‘VI’ or ‘FF/VI’) achieved an improvement in their asthma control compared with patients who continued to take their usual care medicines. Usual care treatment included inhaled corticosteroids (ICS) administered as monotherapy or as ICS/LABA (Long Acting Beta Agonist) combinations. For the primary effectiveness analysis, at 24 weeks a significantly higher percentage of patients with uncontrolled asthma and initiated on treatment with FF/VI achieved better control of their asthma (71%) measured by the Asthma Control Test (ACT), compared with patients continuing usual care treatment (56%), (Odds ratio 2.00, 95% CI 1.70, 2.34; p<0.001). Improvement was defined as an ACT total score ≥20 or an increase from baseline of ≥3. Statistically significant findings were also seen at 12, 40 and 52 weeks. Lead Investigator, Ashley Woodcock, Professor of Respiratory Medicine and Clinical Director for Respiratory Medicine, University Hospital of South Manchester and University of Manchester said: “I am really excited to see the results from SLS asthma. Asthma control continues to be a real challenge for patients and the healthcare community. Poor control can have a major impact on the lives of asthma patients. The effectiveness of different treatments on asthma control is difficult to investigate in a traditional double-blind randomised control trial, where the study design and intrusive monitoring can influence the behaviour of patients. In SLS, patient relevant outcomes are the major endpoints. GSK should be congratulated for running this unique study, designed to understand how asthma medicines work in everyday clinical practice.” In the study for the intent-to-treat (ITT) population, the incidence of serious adverse events (SAE) was the same in both arms (FF/VI 13% and usual care 13%). Pneumonia was a safety endpoint of special interest and a regulatory post-authorisation requirement of the European Medicines Agency (EMA). A novel aspect of the study design was that it allowed patient’s treatment to be modified throughout the study. Therefore two assessments relating to pneumonia have been performed, one based on the arm to which patients were randomised, the second based upon the treatment to which patients were exposed at the time of the event. Serious adverse events of pneumonia by randomised group were reported by 39 patients (FF/VI arm 23, 1%; usual care arm 16, <1%). These patients had 42 events and based on a pre-planned analysis non-inferiority of FF/VI to usual care was not confirmed. When these events were summarised according to the actual treatment patients were taking at the time of the event, 21 events were recorded for FF/VI and 21 events for usual care. Eric Dube, Senior Vice President and Head, Global Respiratory Franchise GSK, said: “Despite medical advances, more than half of patients with asthma continue to experience poor control and significant symptoms. The primary endpoint of this study showed that patients initiated with Relvar Ellipta treatment had twice the odds of achieving an improvement in asthma control compared with patients continuing usual care in this study in everyday clinical practice. This study has been a tremendous partnership effort between healthcare professionals, patients, academics and GSK and we would like to thank everyone who has helped to make this unique study possible.” Michael W. Aguiar, President and Chief Executive Officer of Innoviva said: “We are delighted to see the positive results from a second SLS study with Relvar Ellipta, the first being in chronic obstructive pulmonary disease. Asthma control remains a significant unmet medical need in the daily lives for many patients. We believe that this positive real world data successfully builds upon the previous clinical data to provide strong evidence of the benefits of Relvar Ellipta for the treatment of asthma.” These data will be presented in future publications and will be made available on clinicaltrials.gov. The Salford Lung Study is a Phase III multi-centre, open label randomised controlled trial (RCT). The objective of this study was to compare the effectiveness and safety profile of initiating treatment with FF/VI with usual asthma maintenance therapy over a 52 week period. All suitable patients with asthma at 74 primary care sites in and around Salford and South Manchester, UK, were identified from practice databases and invited to participate in the study by their own GP. The primary endpoint of the study was measured at week 24 in the primary effectiveness analysis population. In total, 4,233 patients with asthma who were taking an inhaled corticosteroid (ICS) with or without a long acting beta -agonist (LABA) were randomised to receive either FF/VI or to continue on their existing asthma maintenance therapy (usual care). Usual care was prescribed by the patients GP and included ICS either alone or in a combination with a LABA. In the usual care arm 36% of patients were on an ICS alone and 64% were on an ICS/LABA combination at the time of commencing study medication. The Salford Lung Study had minimal exclusion criteria and involved a broad demographic of patients. At baseline patients had a mean age of 49.8 (min 18 years) and were split by gender (males vs. female 41/59%). To enrol in the study, patients were required to have a GP diagnosis of asthma as their primary respiratory disease and be receiving maintenance therapy with an ICS with or without LABA for at least 4 weeks prior to visit 2. At baseline 72% of patients had uncontrolled asthma with an ACT total score of 5 to 19. Patients were followed for a period of 52 weeks in a normal clinical practice setting using their electronic medical record (EMR), linking primary care, secondary care and pharmacy data to collect study data. Throughout the duration of the study physicians were allowed to modify or switch treatment at any point as this would happen in normal clinical practice, the only exception being a switch from usual care to FF/VI. At weeks 12, 24, and 40 patients were telephoned to enquire about whether they had experienced any serious adverse events or non-serious adverse drug reactions. On these telephone calls patients were asked to provide responses to the ACT. At month 12 a face to face visit was carried out. The Standardised Asthma Quality of Life Questionnaire (AQLQ[S]) was also conducted at week 24 and week 52 by telephone. The study team was able to monitor all hospital admissions, outpatient and emergency department visits, as well as data from primary care (including all healthcare contacts, out-of-hours activity and prescriptions of antibiotics or oral steroids) via the electronic health records. The Intent-to-Treat (ITT) population is defined as all patients who have been randomised and received at least one prescription of study medication (e.g., FF/VI or usual asthma maintenance therapy). The primary effectiveness analysis (PEA) population is defined as all ITT patients who have an ACT total score of < 20 at baseline (Randomisation Visit). The odds ratio expressed in the results is calculated as the ratio of the odds of achieving better asthma control as a patient initiated with Relvar Ellipta and the odds of achieving better asthma control as a patient continuing on usual care. This value is adjusted for any imbalances between the treatment arms in certain key characteristics. The study design protocol paper can be found on clintrials.gov. The ACT is a well recognised instrument that is used globally in asthma treatment guidelines to assess asthma control. It is self-administered utilising 5 questions to assess asthma control during the past 4 weeks on a 5-point categorical scale (1 to 5). By answering all five questions, a patient with asthma can obtain a score that may range between 5 and 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that a patient’s asthma is poorly or not well controlled. A score of 20 to 25 suggests that a patient’s asthma is likely to be well controlled. The total score is calculated as the sum of the scores from all 5 questions, provided all scores are non-missing; if any individual scores are missing then the overall score will be set to missing. A change of 3 points is clinically meaningful for the patient. The Salford Lung Study is intended to enable healthcare professionals and decision makers to more fully assess the potential value of FF/VI by providing data collected in a normal clinical practice setting which is representative of how healthcare professionals and patients may use the medicine in everyday life. It will add to the existing data set from double blind randomised clinical trials (RCTs) for the medicine which, while critical to establishing the safety and efficacy of a medicine, are conducted in a highly controlled environment and enrol a more highly selected patient population than would be expected in everyday clinical care. The study is made possible through a unique collaboration between GSK, North West e-Health (NWEH), The University of Manchester, Salford Royal NHS Foundation Trust, University Hospital of South Manchester (UHSM), NHS Salford and GPs and community pharmacists in Salford, Trafford and South Manchester. The Salford Lung Study in COPD reported findings in May 2016. This is the second of the two Salford Lung Studies to report. Asthma is a chronic lung disease that inflames and narrows the airways. Asthma affects 358 million people worldwide. The causes of asthma are not completely understood but likely involve an interaction between a person’s genetic make-up and the environment. 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 patients 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: Full US prescribing information, including BOXED WARNING and Medication Guide is available at us.gsk.com or US Prescribing Information for Breo Ellipta. 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 – 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. ANORO, BREO, RELVAR and ELLIPTA are trademarks of the GlaxoSmithKline group of companies. 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 Principal risks and uncertainties in the company's Annual Report on Form 20-F for 2016. 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. 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, 2016, which is 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 Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, to be filed with the SEC in the second 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).
News Article | November 16, 2016
INGELHEIM, Germany--(BUSINESS WIRE)--Boehringer Ingelheim welcomes the updated 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Strategy which now positions a combination of a LAMA (long-acting anticholinergic) and a LABA (long-acting beta2-agonist), as a mainstay treatment for people with Chronic Obstructive Pulmonary Disease (COPD) in GOLD groups B-D.1 This represents a significant change versus previous GOLD guidelines.1 The new Strategy classifies people with COPD by symptoms and history of exacerbations only. It still uses the A, B, C, D system, with each category having its own treatment algorithm supporting a more tailored approach addressing patient needs. For GOLD groups B-D, LAMA/LABA therapy plays a critical, central role in the treatment recommendations.1 "This is a major revision of the GOLD document since 2011 and is a step forward for individualised COPD management. The updated pharmacotherapy recommendations are now based solely on two factors, symptoms and exacerbation history," said Professor Claus Vogelmeier, MD, Chair, GOLD Science Committee, Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Germany. "Our 2017 Global Strategy aims to help people with this chronic but treatable condition by offering holistic treatment guidance that covers pharmacological and non-pharmacological treatments." The 2017 GOLD Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease reflects the latest evidence from published scientific research.1 The added benefits of treatment with a LAMA/LABA beyond the monocomponents alone, and versus LABA/ICS (inhaled corticosteroids) for people with COPD, have been consistently confirmed by a number of randomised, clinical trials.2,3,4,5,6,7,8,9 The evidence includes results from the large-scale, Phase III TOviTO® clinical trial programme. The data also demonstrate Spiolto® Respimat® (tiotropium+olodaterol) provides significant improvements in patient outcomes over Spiriva® Respimat® (tiotropium), right from the initial stages when people with COPD need maintenance therapy.6,7,8,10,11 The new GOLD Strategy provides clear guidance on when, and in which patients, ICS can be added or withdrawn.1 All COPD patients should be treated with therapies that optimise lung function first. Only those who have ≥2 exacerbations per year or ≥1 exacerbation leading to hospital admission may be considered for an ICS-containing therapy after LAMA/LABA. In addition, the new GOLD Strategy suggests that ICS therapy may be withdrawn safely in people with COPD who are in GOLD group D and stable, by using a LAMA/LABA regimen.1 Several studies, including the Withdrawal of Inhaled Steroids During Optimised bronchodilator Management (WISDOM) study,12,13,14,15 have helped inform the de-escalation path. “Boehringer Ingelheim is pleased that our extensive, ongoing clinical trial programme in COPD has contributed to the latest GOLD Strategy. We are committed to continuing research into the optimal management of COPD to achieve the best possible outcomes for people with COPD,” said Dr William Mezzanotte, MD MPH, Vice President and Head of Respiratory Medicine at Boehringer Ingelheim. COPD is a serious but manageable lung disease, which is estimated to affect 210 million people worldwide.16 Total deaths from COPD are projected to increase by more than 30 percent in the next 10 years; COPD is predicted to become the third leading cause of death globally by 2030.17 Once daily Spiolto® Respimat® is Boehringer Ingelheim’s advance in COPD maintenance treatment, and has been approved in more than 50 countries worldwide. For ‘Notes to Editors’ and ‘References’ please visit: http://www.boehringer-ingelheim.com/press-release/boehringer-ingelheim-welcomes-central-role-lamalaba-therapy-within-2017-gold-strategy
News Article | February 16, 2017
INGELHEIM, Germany--(BUSINESS WIRE)--Boehringer Ingelheim today announced that the U.S. Food and Drug Administration (FDA) approved tiotropium Respimat® (marketed as SPIRIVA® Respimat®) for the long-term, once-daily maintenance treatment of people with asthma aged 6 years and older who continue to experience symptoms despite their other maintenance therapy – usually either inhaled corticosteroid (ICS) alone, or a combination of inhaled corticosteroids/long-acting beta agonists (ICS/LABA).1 This approval reflects the comprehensive tiotropium Respimat® paediatric clinical trial programme, involving 905 children aged 6-11 years, conducted by Boehringer Ingelheim.2,3,4 Tiotropium Respimat® is part of a class of medicines called long-acting muscarinic antagonists (LAMA) and is the only one of its kind approved for asthma. It works differently from other treatment options by complementing other maintenance therapies (usually ICS/LABA) to open the airways, which helps people breathe better and reduces asthma attacks, also known as exacerbations. “This FDA approval expands the US indication for tiotropium Respimat® to a broad range of patients, including children, adolescents and adults in the US who may suffer from symptomatic asthma despite taking other maintenance therapies,” said Dr William Mezzanotte, Vice President and Head of Respiratory Medicine at Boehringer Ingelheim. “The expansive paediatric programme within the comprehensive UniTinA-asthma® clinical trial programme, reflects the ongoing commitment of Boehringer Ingelheim to providing innovative solutions for children and adults living with asthma and other serious respiratory diseases.” In the comprehensive, large-scale UniTinA-asthma® clinical trial programme, tiotropium Respimat® demonstrated proven efficacy and safety as an add-on therapy for children, adolescents and adults with asthma.1,5,6,7,8,9,10,11,12,13 Tiotropium Respimat® is delivered via Respimat®, the only inhaler that actively* delivers a propellant-free mist, meaning a person just needs to take a slow deep breath in for the medication to go deep into the lungs.14,15,16,17,18,19,20 Previously, in September 2015, tiotropium Respimat® was approved in the US for the long-term, once-daily, prescription maintenance treatment of asthma in people aged 12 and older.1 Tiotropium Respimat® was approved in the EU in 2014 as an add-on therapy for adults (aged 18 and older) with asthma. For more information please visit http://www.boehringer-ingelheim.com/press-release/ASTHMA-FDA-Expanded_Approval_of_Tiotropium_Respimat® This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products varies from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. SPIRIVA® Respimat® is currently NOT APPROVED for use in children and adolescents under 18 years of age in the EU. SPIRIVA® Respimat® has been approved for use in asthma in over 50 countries, including in the EU, U.S. and Japan. The label varies by country. Please refer to the local product information. * Respimat® delivers a metered dose of medication in a mist at the push of a button not requiring the force from the patient’s inhalation
News Article | November 24, 2015
One night while watching TV, Chris Kunkel decided to kill himself. “Out of nowhere, it just came over me,” Kunkel told me over the phone. He found a bottle of Tylenol PM in the medicine cabinet, swallowed the contents, and put himself to bed. Kunkel was home alone; his wife and two kids were out of town visiting family, but he was on call for work as an army IT specialist and had to stay behind. He had a great life, and no history of depression or mental illness of any kind. The dark thought simply bloomed in his mind, as natural as any other. “It was like thinking, ‘I’m going to go outside for a smoke,’ or ‘I’m going to go to the bathroom,’” Kunkel said. “Except it was: ‘I’m going to kill myself.’” Luckily, Kunkel’s wife arrived home shortly after he downed the fistful of pills. She had decided to come home early to surprise him and found him unconscious next to the empty bottle. She called 911. In the hospital the next morning, Kunkel said he struggled to piece together the events of the night before. “It took awhile for the cobwebs to clear and for me to realize what had happened, and it was tough to try to explain,” Kunkel said. “Really it wasn’t until we got home that we realized that the Chantix probably played a major part.” Kunkel had recently started taking Chantix, a prescription drug intended to help people quit smoking. It worked: Kunkel did quit smoking. He went from a seven-year, pack-a-day habit to cold turkey just 10 days after his first pill. Ten days after that, he tried to kill himself. His story isn’t unique. Since entering the market in 2006, hundreds of Chantix users have reported a laundry list of disturbing effects ranging from intense nightmares, to amnesia, to suicidal (and even homicidal) thoughts and behavior. There were enough reports that the Food and Drug Administration ordered Pfizer, the maker of Chantix, to include a black-box warning label, the strictest possible labeling requirement. Yet dozens of scientific studies have failed to find any link between Chantix and adverse psychiatric effects. These are not just Pfizer’s in-house trials, but independent double-blind, placebo-controlled studies, focused observational studies, and sweeping meta-analyses. These are studies published in illustrious journals like The Lancet and the BMJ. While some of these results come from researchers with ties to Pfizer, many do not, and all of the studies I reviewed came to the same consensus: there’s no evidence Chantix is linked to adverse psychiatric events. How can there be such a gulf between what the science is indicating and what the population is reporting? Testimonies from former Chantix users like Kunkel make it difficult to come to any conclusion other than the one he came to: that Chantix caused him to have suicidal thoughts. But a review of the scientific literature has the exact opposite effect: one can’t help but conclude that something else is causing these people to feel like they’re losing control. The truth is difficult to pin down, and it’s made Chantix a unique case study in how we view prescription drugs, scientific proof, and addiction. And it raises a sobering question: When it comes to risk, can we ever be truly sure that a drug is safe? “That’s where the trouble really started.” Ten years ago, on a Wednesday in November, Pfizer filed an application with the FDA for approval of a new drug to help people quit smoking. Included in that application was a stack of pre-market trials Pfizer had completed, testing the drug on more than 4,500 patients, many for a full year. The worst side effects that were reported were intense, vivid dreams and some nausea, but no serious psychiatric events emerged. “In addition to being efficacious, varenicline appeared to be well tolerated by most participants,” read a report based on these clinical trials published in the Journal of the American Medical Association the summer after the FDA approved Chantix. “Nausea, the most common complaint, was reported as being mostly mild to moderate in severity and rarely resulted in discontinuation of study medication. [...] Varenicline may represent an advance in the treatment of tobacco dependence.” And the drug proved very effective in helping people kick their tobacco habits: after one year, 23 percent of participants were still tobacco-free, and hadn’t taken a single puff since quitting, even though they were only given the drug for the first twelve weeks. Compared to other smoking cessation treatments—nicotine patches and gum, for example, have about a 6 percent success rate—this was remarkable. Varenicline, the drug Pfizer would market as Chantix, is a combination of nicotinic partial agonist and antagonist. Agonist means it stimulate receptors in the brain, and antagonist means it blocks those receptors from being stimulated by other chemicals. Chantix does both. When a smoker takes a puff of a cigarette, the nicotine in the smoke is absorbed through the lungs into the bloodstream, hitching a ride to the brain. The nicotine binds to nicotonic receptors in the brain, which causes a release of dopamine, giving the brain a feeling of reward. It’s a short-lived little high that helps contribute to the addictive qualities of tobacco. Varenicline works by binding to those receptors before the nicotine can get there, which does two things to help someone quit smoking. First, it causes the brain to release a little bit of dopamine (about 40 percent of what nicotine would, that’s the “partial” part of a partial agonist), which helps curb the craving for a cigarette—your brain already got its dopamine reward, so it’s not seeking it from another source. Second, it blocks nicotine from being able to bind to those receptors (that’s the antagonist function), so even if you do smoke, the nicotine doesn’t have the same effect. In May, 2006, the FDA gave the green light to start marketing Chantix. “Initially, there was tremendous uptake. There was just a huge, pent-up demand of these drugs,” said Dr. Frank T. Leone, the director of comprehensive smoking treatment programs at the University of Pennsylvania’s Abramson Cancer Center. (Leone has no affiliation to Pfizer and his research, which focuses on smoking cessation tactics and nicotine addiction, has never been funded by Pfizer.) Varenicline is not the only smoking cessation drug on the market (Zyban, or bupropion, is another popular choice that’s been around since 1997) but with a slightly higher success rate than its predecessor, it quickly became one of the most frequently prescribed drugs in the world. Since it came on the market in 2006, Chantix has been prescribed to more than 11 million unique patients in the US and more than 22 million unique patients globally, according to Pfizer. Leone said Chantix followed a similar arc to Zyban, with an initial burst of popularity that later fizzled out. “The sales would go through the roof, and then shortly after, sales would taper off when comments about weird side effects emerged,” Leone said. For Chantix, the honeymoon ended a little more than a year after the drug hit the market. It started with a smattering of online posts from users claiming they were having suicidal thoughts after taking the drug. It hit a climax with the death of Carter Albrecht. Albrecht was a musician best known for his work as a keyboardist and guitarist for the New Bohemians. In August 2007, Albrecht started taking Chantix. A week later, after a night of drinking, he started behaving erratically, yelling at and attacking his long-time girlfriend. When she locked him out of the house, he went to the neighbor’s and began yelling at the house from the yard. The neighbor fired a “warning shot” through the door, which struck Albrecht in the head and killed him. Albrecht’s girlfriend and family publicly blamed Chantix for his sudden change in behavior and subsequent death. His parents even tried to sue Pfizer. After Albrecht’s death, the FDA began receiving hundreds of reports through its adverse events reporting system, a kind of hotline where anyone can report side effects for any drug. By November, 2007, the reports had totaled enough that the FDA alerted the public, launched an investigation, and ordered Pfizer to update its label. In 2009, as the reports from the public continued to mount—hundreds of adverse effects have been reported each year since Albrecht’s death—the FDA ordered Pfizer to add a black box warning. A black box warning is the most severe labeling requirement the FDA has, and is “designed to call attention to serious or life-threatening risks,” according to the agency. The warning Pfizer is required to use on all of its Chantix literature, including a large disclaimer on its website, includes pretty ominous language warning patients that “some people have had changes in behavior, hostility, agitation, depressed mood, suicidal thoughts or actions while using Chantix to help them quit smoking.” Chantix's alleged dark side was a topical enough to warrant a Saturday Night Live skit. At the same time as it issued the black box warning, the FDA ordered Pfizer to do trials specifically looking for evidence of neuropsychiatric adverse events, and how the drug affects people with existing mental health issues. “I never thought that it would give me the results that it did, that it would throw my life into complete disarray,” said Derek De Koff, a journalist who penned a feature for New York magazine in early 2008 on his experience using Chantix. De Koff wrote that he had bizarre, vivid nightmares, that he felt tired, paranoid, and depressed. He wrote that he contemplated suicide without even really grasping that that’s what he was doing. “Maybe I should just go downstairs and leap in front of a tour bus,” De Koff wrote, recalling his experience. “Or launch my head through the computer screen. All this seemed logical, but also weirdly funny, even at the time: I could see how crazy these impulses were, I could recognize them as suicidal clichés. But I couldn’t make them go away.” De Koff still believes Chantix was responsible for his dark thoughts and feelings—he hasn’t experienced any since going off of the drug seven years ago. In his story, he questioned the quality of the premarket trials of varenicline, which were limited by only including people who had no history of certain illnesses including depression and alcohol and drug abuse. De Koff told me he still thinks the initial results were flawed because of this limitation. “Somebody who smokes a lot, there’s a very good chance they drink as well and there were no studies as to how this drug would impact somebody who was drinking,” De Koff said. “A lot of the stories come from people who were on Chantix and drinking. It’s a dangerous mix, or it was a dangerous mix for me. That’s where the trouble really started.” When the concern about Chantix’s possible dark side first started to build, the only data we had to rely on about varenicline were these consumer reports and Pfizer’s few premarket trials. There wasn’t enough information to say with any certainty whether Chantix was causing these sometimes terrifying symptoms. But we’ve come a long way since then. The FDA’s adverse effects reporting system is a useful tool for the agency. It’s a quick and easy way for patients, doctors, and families to report any potential side effects. If reports start to show a pattern, it’s usually a clue that more scientific research needs to be conducted. The reports on Chantix show a definite pattern. From January 1 of this year to October 16, the Food and Drug Administration received 1,811 reports of adverse effects attributed to varenicline, according to documents obtained by Motherboard through a Freedom of Information Act request. Of those, 98 included suicidal thoughts, 18 reported a completed suicide, and two reported a homicide. Some of the reports filed through the FDA's adverse event reporting system. It’s disturbing to read through hundreds of cold, clinical reports dotted with terms like “nightmare,” “hallucination, auditory,” and “completed suicide.” But it’s important to view these reports in context: these are anecdotal, unproven associations. They can’t be taken as proof of a causal relationship. Just as an anti-vaxxer could report autism as a side-effect of the MMR vaccine, anyone can report any symptom and attribute it to Chantix. “It’s completely uncontrolled and anyone can call in and say ‘I had this effect while taking Chantix,’” said Suzanne Colby, a tobacco researcher and the associate director of the center for alcohol and addiction studies at Brown University. Colby has no affiliation with Pfizer and none of her research has ever been funded by Pfizer (nor any other drug company, she noted). “When you don’t see these effects in the context of controlled trials but you do see it reported in this type of database, it makes me think it’s not the Chantix," Colby said. "As a scientist, that’s my conclusion.” Though the scientific literature has shown Chantix can cause abnormal dreams (the kind of intense nightmares often reported by users), this has been a long-known side effect, one that was evident in Pfizer’s original drug application. When it comes to the reported paranoia, dark thoughts, and suicide attempts linked to Chantix, there are dozens of studies that fail to show a connection. A massive study published in last month’s issue of The Lancet: Respiratory Medicine pulled data from the National Health Service in the UK to look for evidence of a link between Chantix and neuropsychiatric risks as well as cardiovascular risks. Looking at more than 160,000 patients, the researchers found no increased risk of neuropsychiatric events when compared to bupropion (the other popular stop smoking drug) or nicotine replacement therapy (things like the patch and gum). (Two out of the six study authors have received grants from Pfizer, though those grants were not used on this study.) Earlier this year, a review of the current scientific literature on varenicline was published in Nicotine & Tobacco Research. The review was written by Dr. John Hughes, who has previously received funding from Pfizer, but is also considered one of the foremost experts on nicotine. Hughes looked at 46 studies, 41 of which were not funded by Pfizer, specifically looking at suicidal outcomes. He found the studies consistently showed no increased risk of suicide with varenicline, and in the handful where there was an increased risk, it was very low. And if the Pfizer affiliations are making you suspicious, there are plenty of examples of completely independent studies finding the same results. A study published in the February issue of BMJ reviewed 39 trials involving 5,817 patients who were taking Chantix and 4,944 patients taking placebos. The researchers found “no increased risk of suicide or attempted suicide, suicidal ideation, depression, or death in individuals treated with varenicline.” None of the study authors have any affiliation with Pfizer or have received any funding from Pfizer. A study from 2013, also with no ties to Pfizer, looked at 120,000 patients undergoing some form of smoking cessation treatment and found no evidence of association between varenicline and an increased risk of suicide or depression. There are also studies that focus on specific groups, like people with schizophrenia or bipolar disorder. Even with pre-existing neuropsychiatric issues, researchers found no risk of adverse effects linked to Chantix. Colby suspects there are a number of factors that could be leading to the reports of negative side effects, ranging from fodder for courtroom defenses to the very real side effects of nicotine withdrawal. The fact is that Chantix is a pretty effective stop-smoking aid, so many people who report scary side effects have recently kicked two or three-pack-a-day habits, and that takes a toll on the brain, Colby said. “The most common things are cravings, irritability, frustration, sleep disturbance, difficulty concentrating, negative affect generally, depression,” Colby said. “For people who have various forms of mental illness, maybe those are exacerbated. These things that happen very idiosyncratically, how do we know that it’s the Chantix versus something that would have happened anyway? The only way to answer that question is with clinical trials.” It’s worth noting that Pfizer’s fingerprints are littered throughout the scientific literature—it’s a bit of a hazard with this field of study, in general. Many studies have one or more authors with some kinds of ties to the company, ranging from accepting research grants from Pfizer to testifying as expert witnesses for Pfizer in court. This doesn’t mean the studies are invalid, but it does show Pfizer clearly is investing a lot of money into studying, and possibly exonerating, Chantix. And the company's motivations are worth considering. Just weeks after Albrecht’s death, lawyers began advertising for lawsuits. These rounds of early suits have cost Pfizer millions of dollars in settlements. By February of 2013, the company had settled most of its claims at a total cost of $273 million, according to SEC filings. It estimated it would need to spend another $15 million on the outstanding cases, and a class action suit in Canada is still pending, according to this year’s filing. “Pfizer believes there is no reliable scientific evidence establishing a causal relationship between Chantix and serious neuropsychiatric events,” said Steven Danehy, a spokesperson for Pfizer, in an email. “Smoking is one of the leading preventable causes of death in the world. Stopping smoking is one of the most important steps a person can take to improve their health, and the benefits of quitting are immediate and substantial. However, many people who want to quit struggle to do so without help. The risks of Chantix should be weighed against the benefits of its use.” Pfizer is also just months away from publishing the results of a massive clinical trial looking at the effects of varenicline specifically on patients who have a history of psychiatric disorders, an undertaking requested by the FDA as the agency considers rewording or lifting the black-box warning requirement. “You have a tricky conundrum: you want to be cautious and provide every possible piece of info to the public to help them make a decision, but on the other hand you don’t want to put people off using what is probably the most effective stop smoking method we’ve got,” said Robert West, a professor of health psychology and the director of tobacco studies at University College London. West was a co-author on the Lancet study and has received grants from Pfizer. “You can’t discount the observational data [from consumer reports,]” West continued. “There’s something going on and we don’t know what it is, but when you have a drug taken by millions of people, the laws of chance for this kind of thing are always against you.” Cigarette smoking causes close to half a million deaths in the US annually, according to the Centers for Disease Control and Prevention. Life expectancy for smokers is ten years shorter than nonsmokers, and if you can quit smoking before you turn 40, your chance of dying from a smoking-related disease drops by 90 percent. With a higher effectiveness than any other smoking cessation treatment, Chantix can quite literally extend people’s lives. But the reams of testimonies from patients who have suffered scary, even life-threatening, side effects from the drug online and in the media, combined with the alarming warnings issued by the FDA, could make anyone hesitant to try, and stick with, the drug. And there’s another factor at play. Despite the clear health benefits of quitting smoking, people don’t view Chantix or drugs like it as “life-saving.” We accept the truly awful side effects of treatments like chemotherapy (which include vomiting, mouth sores, diarrhea, and burning sensations) because we know the trade off is the chance for a longer life. But when the benefits of a drug are delayed by years or even decades, like with a smoking cessation aid, we’re less willing to endure any possible negative side effects in the short term. “If we had done this study with anything other than Chantix, I think people would have said ‘yeah, absolutely, fine. No evidence of an effect, we’ll move on. That’s good news,’” West told me via Skype. “But with Chantix, that idea is there." There are also pervasive cultural ideas that might make someone weigh the risks of Chantix more strongly than the risks of continuing to smoke. The public generally perceives addiction as a shortcoming, something you should just be able to overcome on your own. Why would you risk feeling suicidal to fix a problem you really ought to be able to just solve on your own? “It’s a common perspective in smokers and particularly in smokers with substance use disorders,” Colby told me. “And adolescents and young adults in particular are very unlikely to take a pharmacotherapy to quit smoking, because they don’t really perceive smoking as something that should require treatment to quit.” And there’s the issue with proof. Can we ever truly say a drug is 100 percent safe? West said once an idea that a drug is dangerous has made its way into the public consciousness, the burden of proof becomes much higher. Instead of looking for evidence of a relationship between Chantix and negative effects, the researcher is tasked with seeking out evidence that there isn’t a relationship. "It’s probably not related [to neuropsychiatric effects], but the key is in the ‘probably,’ because you can’t say definitely,” West said. “How do you prove a negative? You can’t.” The FDA assesses drug risks all the time. If it thinks there is enough evidence that a drug causes more harm than good, it pulls it from the market (and that’s if a drug company hasn’t already pulled it). The FDA’s label requirements on Chantix aren’t proof that the drug causes people to come undone, it’s just relaying the information we have: there have been reports of serious neuropsychiatric adverse effects. Thousands of reports. And at the end of the day, there’s no way to know for sure that a drug is 100 percent safe for every person. As for Kunkel? He stopped taking Chantix and started smoking again as soon as he got home from the hospital, but recently quit by switching to vaping. He told me he hasn't had any issues with depression or suicidal thoughts since he stopped taking Chantix. “I truly believe it just depends on the person, ” Kunkel said. “Everyone’s built differently.” Lit Up is a series about drugs and drug-like substances and practices. Follow along here.
News Article | December 9, 2016
MELBOURNE, Australia, Dec. 09, 2016 (GLOBE NEWSWIRE) -- Adherium Limited (ASX:ADR), a global leader in digital health technologies that address sub-optimal medication use in chronic disease, today announces that some of Europe’s most prestigious clinical opinion leaders have chosen Adherium’s Smartinhaler™ for the myAirCoach programme, part of the European Union’s Horizon 2020 Framework for Research and Innovation. The myAirCoach programme is being funded through the Horizon 2020 framework which is the largest EU Research and Innovation programme ever established with nearly €80 billion of funding available over 7 years (2014 to 2020). The purpose of the myAirCoach programme is to establish whether home monitoring and mobile health (mHealth) systems can be used to predict asthma control and the occurrence of asthma exacerbations. One of the main goals of the project is to help patients manage their health through user-friendly tools that will increase awareness of their clinical state as well as the adherence and effectiveness of the medical treatment they follow. The impact of the myAirCoach programme is expected to set the basis for the widespread adoption of sensor-based self-management systems across the spectrum of respiratory diseases. (Source: http://www.myaircoach.eu/myaircoach/content/what-myaircoach-project) Smartinhaler™ is already proven to reduce hospitalisation as demonstrated in the results of the year-long STAAR study, recently published online in the prestigious peer-reviewed medical journal Thorax . The study revealed a significant reduction in hospital admissions over the course of 12 months as well as substantial other health and quality of life benefits for patients using Smartinhaler™. The data from the STAAR study builds on a study published in January 2015 in The Lancet Respiratory Medicine  which showed the use of the Smartinhaler™ platform increased adherence to preventative medication by 180% and reduced use of reliever medication by 45%. “Successful disease management and prevention is only truly achieved by understanding the real-world complexity of our lives. The best way to do that is through rich data collected in the real world. By providing our innovative solutions to people with asthma, we can help people take the right medicine, at the right dose, at the right time and in the right way,” said Garth Sutherland, Founder & Group CEO of Adherium. “The myAirCoach programme is a leading initiative assessing the impact that digital health solutions, such as Smartinhaler™, can have on patients in a real-world setting. It is a major international project, funded by the prestigious European Union Horizon 2020 framework.” Participating organisations in the myAirCoach project include: Imperial College London, University of Manchester and Leiden University Medical Center. The project is anticipated to run for the next 12 months. Dr. Omar Usmani, Reader in Respiratory Medicine & Consultant Physician, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, said; “The myAirCoach programme will help asthma sufferers to manage their health through user-friendly tools that will increase awareness of their clinical state as well as their adherence and the effectiveness of medical treatment they follow.” Professor Fan Chung, Professor of Respiratory Medicine and Head of Experimental Studies Medicine, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, commented; “People with asthma are more likely to miss school or work and experience reduced quality of life. We are excited about the collaboration between Adherium and myAirCoach which is expected to set the basis for the widespread adoption of sensor-based self-management systems across the spectrum of respiratory diseases.” Adherium will be supplying a range of products to the programme via three key centres, including devices for inhaled medications manufactured by AstraZeneca and GSK: The project is coordinated by the Centre for Research and Technology Hellas (CERTH), Thessaloniki, Greece and is supported by a group of asthma patients acting as advisors. Other participating organisations in the myAirCoach project include: University of Patras, Allertec Hellas SA, IHP Microelectronics, ZorgGemak (MedVision 360BV), European Federation of Asthma & Allergy Associations, Cnet Svenska AB, Circassia and Asthma UK. More information on myAirCoach can be found at the project’s website http://www.myaircoach.eu/myaircoach/  Published online: Thorax doi:10.1136/thoraxjnl-2015-208171  Chan AHY, Stewart AWS, Harrison J, Camargo C, Black PN, Mitchell EA. The effect of an inhaler with ringtones on asthma control and school attendance in children. Lancet Respir Med. 2015;3:210-219 Adherium (ASX:ADR) is an Australian Securities Exchange listed company which develops, manufactures and supplies digital health technologies which address sub-optimal medication use and improve health outcomes in chronic disease. Adherium operates globally from bases in the USA, Europe and Australasia. Adherium is a provider of digital health solutions to patients, pharmaceutical companies, healthcare providers and contract research organizations. The Company’s proprietary Smartinhaler™ platform has been independently proven to improve medication adherence and health outcomes for patients with chronic respiratory disease. Adherium has the broadest range of "smart" medication sensors for respiratory medications globally. The Smartinhaler™ platform has so far been used in more than 65 projects (clinical, device validation or other) and has been referenced in 56 peer reviewed journal articles. Clinical outcomes data has proven that the Smartinhaler™ platform can improve adherence by up to 59% in adults and 180% in children and reduce severe episodes by 60% in adults, leading to improved quality-of-life and demonstrating a substantial gain over current best practice treatment. The Company has received FDA 510(k) notifications for clearance to market and CE Marks for its devices and software, which allows it to sell these devices into international markets.
News Article | December 7, 2015
Whole Genome Sequencing is a faster, cheaper and more effective way of diagnosing tuberculosis says a new study published in the journal Lancet Respiratory Medicine. Dr. Louise Pankhurst of the University of Oxford and a team of worldwide collaborators including Public Health England utilised innovative DNA technology to diagnose cases of tuberculosis (TB) up to eight times faster than traditional methods. While Whole Genome Sequencing has been previously used in TB research studies, this is the first time the technology was applied in real world scenarios. The researchers at Oxford's John Radcliffe Hospital were able to detect presence of TB and whether it was resistant to commonly used antibiotics within one week – up to eight times faster than utilising traditional diagnosis methods. In addition to facilitating faster and more targeted treatment of people with TB, the speedy diagnosis also meant the scientists were able to detect and respond to potential outbreaks as they happen. The innovative technology also proved more cost effective, at an average cost of £481 per positive case, compared to £517 per case using current technologies. The stunning results of this trial have implications for TB prevention in the UK. It was funded by the Health Innovation Challenge Fund (HIC Fund) and supported by the NIHR Oxford Biomedical Research Centre and the NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance. The new technique will be adopted by Public Health England (PHE) and is expected to reduce transmission of TB. Tuberculosis is a major part of PHE's strategy for infectious diseases due to some increases in incidence and emergence of multi-drug resistant infections. PHE is also working with Genomics England as part of the 100,000 Genomes Project to further understanding of why some people develop severe reactions to infections. Lead author Dr. Louise Pankhurst, University of Oxford, said: 'This is a really exciting time to be working in infectious disease research. The UK is poised to become the first country in the world to replace traditional tuberculosis diagnosis with whole genome sequencing. Our study has shown how this will dramatically speed up the time taken to diagnose TB, helping patients be placed on the most effective treatment as soon as possible and reducing the risk of disease transmission.' Professor Derrick Crook, Director of the Public Health England National Infections Service said: 'This ground-breaking research provides a roadmap for faster, cheaper and more effective diagnosis of TB, and is a crucial step in Public Health England’s goal of eliminating TB as a public health problem in England. 'This marks a significant milestone in the way we tackle TB, yet things are going to get better as whole genome sequencing technology is rapidly becoming much faster and less expensive and will ultimately inform the way we deal routinely with all infectious disease diagnosis.'
News Article | November 28, 2016
Doctors in Scotland are working to improve mesothelioma diagnosis by creating a list of biomarkers to identify the disease. Surviving Mesothelioma has just posted an article on the newly-announced study. Click here to read it now. The trial will involve up to 120 pleural mesothelioma patients as well as 480 people with other pleural diseases and 109 asbestos-exposed people. Everyone involved in the trial will submit a blood sample and undergo a clinical exam. “Blood levels will be compared with paired pleural fluid levels and malignant pleural mesothelioma tumor volume (using MRI) in a nested substudy,” explains researcher Selina Tsim of the Department of Respiratory Medicine at Queen Elizabeth University Hospital in Glasgow. The trial announced in the British Medical Journal’s open access online-only journal BMJ Open will be carried out at 22 recruiting centers across Scotland. “There is a tremendous need for more reliable biomarkers for mesothelioma diagnosis and prognosis, especially since diagnostic procedures like thoracoscopy are not available everywhere and are expensive,” says Alex Strauss, Managing Editor of Surviving Mesothelioma. Learn more about the new biomarker study, including some of the biomarkers researchers will be looking at closely, in the article New Clinical Trial Aims to Create Bioresource for Improved Mesothelioma Diagnosis, now available on the Surviving Mesothelioma website. Tsim, S, et al, “Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study”, November 24, 2016, BMJ Open, http://bmjopen.bmj.com/content/6/11/e013324.full For nearly ten years, Surviving Mesothelioma has brought readers the most important and ground-breaking news on the causes, diagnosis and treatment of mesothelioma. All Surviving Mesothelioma news is gathered and reported directly from the peer-reviewed medical literature. Written for patients and their loved ones, Surviving Mesothelioma news helps families make more informed decisions.