Jeppesen P.B.,Rigshospitalet |
Messing B.,Hopital Beaujon Service de Gastroenterologie et Assistance Nutritive |
Iyer K.,Mount Sinai Medical Center |
Seidner D.L.,Vanderbilt University |
And 4 more authors.
Gastroenterology | Year: 2012
Background & Aims: Teduglutide, a glucagon-like peptide 2 analogue, might restore intestinal structural and functional integrity by promoting growth of the mucosa and reducing gastric emptying and secretion. These factors could increase fluid and nutrient absorption in patients with short bowel syndrome with intestinal failure (SBS-IF). We performed a prospective study to determine whether teduglutide reduces parenteral support in patients with SBS-IF. Methods: We performed a 24-week study of patients with SBS-IF who were given subcutaneous teduglutide (0.05 mg/kg/d; n = 43) or placebo (n = 43) once daily. Parenteral support was reduced if 48-hour urine volumes exceeded baseline values by <10%. The primary efficacy end point was number of responders (patients with >20% reduction in parenteral support volume from baseline at weeks 20 and 24). Results: There were significantly more responders in the teduglutide group (27/43 [63%]) than the placebo group (13/43 [30%]; P =.002). At week 24, the mean reduction in parenteral support volume in the teduglutide group was 4.4 ± 3.8 L/wk (baseline 12.9 ± 7.8 L/wk) compared with 2.3 ± 2.7 L/wk (baseline 13.2 ± 7.4 L/wk) in the placebo group (P <.001). The percentage of patients with a 1-day or more reduction in the weekly need for parenteral support was greater in the teduglutide group (21/39 [54%]) than in the placebo group (9/39 [23%]; P =.005). Teduglutide increased plasma concentrations of citrulline, a biomarker of mucosal mass. The distribution of treatment-emergent adverse events that led to study discontinuation was similar between patients given teduglutide (n = 2) and placebo (n = 3). Conclusions: Twenty-four weeks of teduglutide treatment was generally well tolerated in patients with SBS-IF. Treatment with teduglutide reduced volumes and numbers of days of parenteral support for patients with SBS-IF; ClinicalTrials.gov Number, NCT00798967. © 2012 AGA Institute.
Jeppesen P.B.,CA 2121 Rigshospitalet |
Pertkiewicz M.,Medical University of Warsaw |
Forbes A.,University College London |
Pironi L.,University of Bologna |
And 7 more authors.
Clinical Nutrition | Year: 2013
Background & aims: Short bowel syndrome (SBS)-intestinal failure (IF) patients have impaired quality of life (QoL) and suffer from the burden of malabsorption and parenteral support (PS). A phase III study demonstrated that treatment with teduglutide, a glucagon-like peptide 2 analogue, reduces PS volumes by 32% while maintaining oral fluid intake constant; placebo-treated patients had reduced PS by 21%, but oral fluid intake increased accordingly. As effects of teduglutide on QoL are unknown, they were investigated here. Methods: QoL analyses from a double-blind, randomised Phase III study in 86 SBS-IF patients receiving teduglutide (0.05mg/kg/day s.c.) or placebo over 24 weeks. At baseline and every 4 weeks, QoL was assessed using the validated SBS-QoL™ scale. Results: PS reductions were associated with QoL improvements (ANCOVA, p=0.0194, SBS-QoL per-protocol). Compared to baseline, teduglutide significantly improved the SBS-QoL™ total score and the score of 9 of 17 items at week 24. These changes were not significant compared to placebo. Teduglutide-treated patients with remaining small intestine >100cm experienced more gastrointestinal adverse events (GI-AE), unfavourably affecting QoL. Conclusions: Overall, PS volume reductions were associated with improvements in SBS-QoL™ scores. The short observation period, imbalances in oral fluid intake in relation to PS reductions, large patient and effect heterogeneity and occurrence of GI-AE in a subgroup of teduglutide-treated patients may account for the inability to show statistically significant effects of teduglutide on SBS-QoL™ scores compared to placebo. ClinicalTrials.gov identifier: NCT00798967. © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.
Bilezikian J.P.,Columbia University |
Khan A.,McMaster University |
Potts Jr. J.T.,Harvard University |
Brandi M.L.,University of Florence |
And 15 more authors.
Journal of Bone and Mineral Research | Year: 2011
Recent advances in understanding the epidemiology, genetics, diagnosis, clinical presentations, skeletal involvement, and therapeutic approaches to hypoparathyroidism led to the First International Workshop on Hypoparathyroidism that was held in 2009. At this conference, a group of experts convened to discuss these issues with a view towards a future research agenda for this disease. This review, which focuses primarily on hypoparathyroidism in the adult, provides a comprehensive summary of the latest information on this disease. © 2011 American Society for Bone and Mineral Research.
News Article | December 9, 2016
Enterome SA, a pioneer in the development of pharmaceuticals and diagnostics based on the gut microbiome, is pleased to announce the appointments of Jai Patel, Ph.D. as Chief Medical Officer (CMO), and Roger J. Garceau, MD as Non-executive Director. Drs Patel and Garceau bring significant experience in clinical pharmaceutical development and reinforce Enterome's leadership team as the Company progresses its lead therapeutic and diagnostic projects, including EB8018 for Crohn's disease, into and through clinical development. Dr. Patel joins Enterome with over 25 years' industry experience and a strong background in international clinical development and regulatory affairs. He was most recently Chief Medical & Scientific Officer at NephroGenex, Inc. and, before that, spent over 20 years at GlaxoSmithKline where he held positions of increasing responsibility, serving as Vice President across R&D disciplines including clinical research, medical affairs and global regulatory affairs. He received his medical training at the University of London and is a member of the UK Royal College of Physicians. Dr. Garceau brings over 30 years' of pharmaceutical development experience to Enterome. He previously served as CMO and Executive Vice President of Research & Development at NPS Pharmaceuticals, Inc. Prior to this, he held executive clinical and development roles at Sanofi-Aventis, Aventis and Pharmacia-Upjohn (Pfizer), where he contributed to a number of successful new pharmaceutical marketing applications. Dr. Garceau received his Doctorate of Medicine from the University of Massachusetts Medical School. Commenting on his appointment, Jai Patel said: "I am pleased to join Enterome at such an important time for the Company. Enterome's unique metagenomics platform has enabled a new way of understanding the gut microbiome and its importance in human health. This platform is identifying novel targets and biomarkers to improve the diagnosis and management of serious diseases. Enterome's lead therapeutic candidate, EB8018, a novel small molecule candidate with a unique mode of action, in particular, is at an exciting stage of development as it approaches clinical trials as a potential new treatment for Crohn disease. The company is also building a pipeline of products with significant potential and I'm very excited to be working with the exceptional team to discover, develop and advance these in the coming years." "Enterome has been expanding rapidly in recent months and continues to make steady progress advancing our pipeline. The appointments of Drs Patel and Garceau, in conjunction with the recent addition of Christophe Bonny as Chief Scientific Officer, significantly enhance the discovery and development, and international corporate development capabilities of the team, and give us great confidence for the further development of the company," added Pierre Belichard, CEO of Enterome. Enterome is pioneering the development of novel pharmaceuticals and diagnostics to support personalized therapies in microbiome-related diseases such as Inflammatory Bowel Disease (IBD), cancer and metabolic diseases. Enterome is also leading the development of new industry standards in gut microbiome quantitative and functional analysis. This technology leadership allows Enterome to open up the new field of therapeutic target discovery in the microbiome in order to address significant unmet medical needs. Enterome has established partnerships with leading pharmaceutical companies and academic research institutes, including Johnson & Johnson Innovation/Janssen Biotech, Takeda and Abbvie in inflammatory bowel and gastro-intestinal diseases; Bristol-Myers Squibb in immuno-oncology; and the Mayo Clinic and Geisinger hospitals in metabolic disorders. The Company was established in 2012 in Paris, France to develop the discoveries made by the INRA metagenomic platform. The Company has raised a total of €32 million from leading venture capital investors (Seventure Partners, Lundbeckfonden Ventures, Health for Life Capital & Omnes Capital) and strategic investors (Nestlé, Shire & INRA Transfert). Additional information about Enterome is available through its website: http://www.enterome.com
News Article | February 21, 2017
BERKELEY HEIGHTS, N.J., Feb. 21, 2017 (GLOBE NEWSWIRE) -- Edge Therapeutics, Inc. (Nasdaq:EDGE), a clinical-stage biotechnology company developing novel hospital-based therapies in the management of acute, life-threatening conditions, today announced the appointment of Alyssa Wyant as Senior Vice President, Regulatory Affairs. Ms. Wyant will oversee all facets of Edge's regulatory activities, providing oversight for all U.S. and international regulatory matters, including filings and interactions with regulatory authorities. Ms. Wyant will report to Edge’s President and Chief Executive Officer, Brian Leuthner, and become part of Edge’s executive team. "We are pleased to have Alyssa join the Edge team. She has extensive regulatory experience and an outstanding track record, having supported the advancement of multiple orphan products through the regulatory approval process, including direct interaction with the U.S. Food and Drug Administration (FDA) and international regulatory agencies for both regulatory approvals and post-approval activities,” said Mr. Leuthner. “Alyssa's experience will be invaluable to Edge as we continue to advance the clinical development of EG-1962 through our Phase 3 NEWTON 2 study for aneurysmal subarachnoid hemorrhage (aSAH), and focus on driving forward pipeline products from our Precisa Platform™ in the years ahead." Ms. Wyant has nearly 20 years of global regulatory experience with a focus on the development, registration and successful launches of innovative, biologic and small molecule orphan disease products. Most recently, Ms. Wyant served as Vice President, Global Regulatory Affairs at PTC Therapeutics. While at PTC, she was responsible for the strategic planning and execution of global regulatory activities for Translarna™ (ataluren) across five orphan disease indications, acting as regulatory agency liaison for approval filings in Duchenne muscular dystrophy (DMD) and cystic fibrosis with the European Medicines Agency (EMA), FDA and Health Canada, and for maintenance of conditional approval for DMD with the EMA. As Senior Director, International Regulatory Affairs at NPS Pharmaceuticals, Ms. Wyant created and implemented global strategies for the registration and post-approval activities for orphan disease products in Europe, North America and Latin America, supporting FDA approval for Natpara® for hypoparathyroidism and the U.S. and EU launches for Gattex® / Revestive® for short bowel syndrome. Earlier in her career, she held multiple leadership positions in global regulatory affairs at Shire Human Genetic Therapies in the U.S. and Switzerland, where she was a key contributor in obtaining, maintaining, and extending registration of the enzyme replacement therapy products Elaprase®, VPRIV® and Replagal®. She also held regulatory affairs positions at Vertex Pharmaceuticals and Genetics Institute / Wyeth-Ayerst Pharmaceuticals. Ms. Wyant has a B.S. in cell and molecular biology from the University of Washington. In connection with Ms. Wyant’s new employment, the Compensation Committee of Edge’s Board of Directors has approved the grant to Ms. Wyant of non-qualified stock options to purchase 80,000 shares of Edge’s common stock. The effective date of the grant is March 1, 2017 and the exercise price for such stock options will be equal to the closing price of Edge’s common stock on such date, as reported by NASDAQ. The grant was made as an inducement material to Ms. Wyant’s acceptance of employment with Edge, in accordance with NASDAQ Listing Rule 5635(c)(4). The options have a 10-year term and vest over a period of four years, with 25 percent vesting on February 21, 2018, which is one year following Ms. Wyant’s date of hire, and the remaining 75 percent vesting in approximately equal monthly increments over the succeeding thirty-six months, subject to Ms. Wyant’s continuous employment through each applicable vesting date. In addition, the options are subject to acceleration or forfeiture upon the occurrence of certain events as set forth in Ms. Wyant’s stock option and / or employment agreements. Edge Therapeutics, Inc. is a clinical-stage biotechnology company that discovers, develops and seeks to commercialize novel, hospital-based therapies capable of transforming treatment paradigms for the management of acute, life-threatening neurological and other conditions. EG-1962, Edge’s lead product candidate, has the potential to fundamentally improve patient outcomes and transform the management of aSAH, which is bleeding around the brain due to a ruptured brain aneurysm. Edge is evaluating EG-1962 in two clinical studies: the pivotal Phase 3 NEWTON 2 study of EG-1962 delivered via external ventricular drain, and a study of direct intracisternal administration of EG-1962. For additional information about Edge, please visit www.edgetherapeutics.com. This press release and any statements of representatives of Edge Therapeutics, Inc. related thereto that are not historical in nature contain, or may contain, among other things, certain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements may include, without limitation, statements with respect to Edge’s plans, objectives, projections, expectations and intentions and other statements identified by words such as "projects," "may," "will," "could," "would," "should," "believes," "expects," "anticipates," "estimates," “seeks,” "intends," "plans," "potential" or similar expressions, including statements with respect to Edge’s future clinical and regulatory plans, Edge’s ability to advance its portfolio of therapies towards commercialization and the potential effects of its products. These statements are based upon the current beliefs and expectations of Edge’s management and are subject to significant risks and uncertainties. Actual results may differ significantly from those set forth in the forward-looking statements. These forward-looking statements involve certain risks and uncertainties that are subject to change based on various risk factors (many of which are beyond Edge's control) as described under the heading "Risk Factors" in Edge’s filings with the United States Securities and Exchange Commission.
News Article | February 16, 2017
Baxalta integration progressing ahead of schedule; Shire now the world leader in rare diseases  Results include Baxalta Inc. (Baxalta) (acquired on June 3, 2016) and Dyax Corp. (Dyax) (acquired on January 22, 2016), unless otherwise noted. Percentages compare to equivalent 2015 period.  The Non GAAP financial measures included within this release are explained on pages 28 - 29, and are reconciled to the most directly comparable financial measures prepared in accordance with US GAAP on pages 22 - 24.  US GAAP net income as a percentage of total revenues.  Percentage point change (ppc).  Diluted weighted average number of ordinary shares 776.2m. "2016 was a transformational year for Shire as we became the world leader in rare diseases. Our innovative portfolio and sharp focus on commercial excellence enabled us to generate double digit pro forma top-line growth, with reported sales of $10.9 billion, while materially advancing the pipeline, successfully integrating Dyax and progressing the Baxalta integration ahead of schedule. "In August we launched XIIDRA in the U.S. with an exceptional new drug launch, demonstrating our strength in commercial excellence and capturing 19% of market share within four months. This marks an outstanding entry into ophthalmics and we aim to further build a leadership position in this therapeutic area. "With multiple product launches planned in 2017, we remain focused on execution and expect to generate strong top- and bottom-line growth. Our pipeline has never been stronger with multiple programs in Phase 3 or registration. We remain extremely optimistic about Shire's long-term growth prospects." We expect 2017 to be another strong year for Shire, building on our excellent financial performance in 2016. In addition to the guidance in the table below, we are providing depreciation and capital expenditure 2017 guidance following the Baxalta acquisition on June 3, 2016. We expect depreciation expense to be $400 - $450 million and capital expenditure to be approximately $1 billion in 2017 reflecting our larger footprint and important investments to support our growth aspirations. The Non GAAP diluted earnings per ADS forecast assumes a weighted average number of 914 million fully diluted ordinary shares outstanding for 2017. Our US GAAP diluted earnings per ADS outlook reflects anticipated amortization, integration and reorganization costs.  For a list of items excluded from Non GAAP Outlook, refer to pages 28 - 29 of this release.  See page 24 for a reconciliation between US GAAP diluted earnings per ADS and Non GAAP diluted earnings per ADS. ADYNOVATE for the treatment of hemophilia A CUVITRU for the treatment of primary immunodeficiency disorders ONIVYDE for the treatment of pancreatic cancer SHP465 for the treatment of ADHD NATPAR for the treatment of hypoparathyroidism VONVENDI for the treatment of adults affected by von Willebrand disease (VWD) On January 3, 2017, Shire announced the appointment of Ian Clark to the Board of Directors. In respect of the six months ended December 31, 2016, the Board resolved to pay an interim dividend of 25.70 U.S. cents per Ordinary Share (2015: 22.16 U.S. cents per Ordinary Share). Dividend payments will be made in Pounds Sterling to holders of Ordinary Shares and in U.S. Dollars to holders of ADSs. A dividend of 20.64 pence per Ordinary Share (2015: 15.32 pence) and 77.10 U.S. cents per ADS (2015: 66.48 U.S. cents) will be paid on April 25, 2017 to shareholders on the register as at the close of business on March 10, 2017. Together with the first interim payment of 4.63 U.S. cents per Ordinary Share (2015: 4.21 U.S. cents per Ordinary Share), this represents total dividends for 2016 of 30.33 U.S. cents per Ordinary Share (2015: 26.37 U.S. cents per Ordinary Share), an increase of 15% in U.S. Dollar terms. Holders of Ordinary Shares are notified that, in order to receive UK sourced dividends via Shire's Income Access Share arrangements ("IAS Arrangements"), they need to have submitted a valid IAS Arrangements election form to the Company's Registrar, Equiniti, by no later than 5pm (BST) on March 24, 2017. Holders of Ordinary Shares are advised that: Internet links to the newly formatted IAS Arrangements election forms can be found at: Dial in details for thelive conference call for investors at 14:00 GMT / 9:00 EDT on February 16, 2017: UK dial in: 0808-237-0030 or 020-3139-4830 US dial in: 1-866-928-7517 or 1-718-873-9077 International Access Numbers: Click here Password/Conf ID: 17162212# Live Webcast: Click here The quarterly earnings presentation will be available today at 13:00 GMT / 8:00 EDT on: OVERVIEW OF FULL YEAR 2016 FINANCIAL RESULTS COMPARED TO FULL YEAR 2015 Product sales increased 78% to $10,886 million (2015: $6,100 million), primarily due to including legacy Baxalta sales since June 2016. Excluding legacy Baxalta, product sales increased 15% (15% at Non GAAP CER). Genetic Diseases product sales increased 12% (14% at Non GAAP CER), primarily driven by increased demand for our HAE therapies. FIRAZYR sales increased 30%, primarily due to an increase in the number of patients on therapy in both the U.S. and international markets. CINRYZE sales increased by 10%, as an increase in the number of patients on therapy was partially offset by reduced utilization as a result of a U.S. supply constraint during the second half of the year. Shire continues to execute on plans to increase CINRYZE production to meet both short-term and long-term patient demand. Neuroscience product sales increased 13% (14% at Non GAAP CER), with growth primarily driven by VYVANSE. VYVANSE sales increased 17% due to prescription growth in the U.S. adult market which includes ADHD and Binge Eating Disorder (BED), the benefit of price increases taken since 2015 and growth in our international markets. Hematology, acquired with Baxalta in June 2016, reported product sales of $2,241 million. Hematology includes sales of recombinant and plasma-derived hemophilia products (primarily factor VIII and factor IX) and inhibitor therapies. Pro forma 2016 growth in Hematology was approximately 2% (3% at Non GAAP CER). Internal Medicine product sales increased 17% (17% at Non GAAP CER), primarily driven by strong growth from LIALDA/MEZAVANT, GATTEX/REVESTIVE and NATPARA. LIALDA/MEZAVANT sales increased 16%, primarily due to an increase in prescription demand, resulting in a U.S. market share of 40% at the end of 2016 (compared to 36% in 2015). GATTEX/REVESTIVE and NATPARA continued to perform well with sales increasing 55% and 250%, respectively, primarily due to an increase in the numbers of patients on therapy. Immunology, acquired with Baxalta in June 2016, reported product sales of $1,516 million. Immunology includes sales of antibody-replacement immunoglobulin and bio therapeutics therapies. Pro forma 2016 growth in Immunology was approximately 8% (9% at Non GAAP CER), at the upper end of the overall market growth trend. Oncology, acquired with Baxalta in June 2016, reported product sales of $131 million. Oncology includes sales of ONCASPAR and ONIVYDE, the latter being approved in the EU on October 18, 2016. Ophthalmology product sales relate to XIIDRA, which was made available to patients on August 29, 2016. XIIDRA contributed $54 million of product sales, primarily due to strong early demand and initial launch stocking. The following table presents full year 2016 Baxalta pro forma sales, assuming the acquisition occurred on January 1, 2015. Growth rates represent the full year 2016 pro forma sales compared to recast full year 2015 pro forma sales as previously reported by Baxalta following its separation from Baxter International Inc. Royalties and Other Revenues increased 61%, primarily due to including $99 million of contract manufacturing revenue acquired with Baxalta. Cost of product sales as a percentage of product sales increased to 34%, primarily due to the impact of higher amortization of inventory fair value adjustments following the acquisitions of Baxalta and Dyax and, to a lesser extent, the impact of lower margin product franchises acquired with Baxalta. Non GAAP cost of product sales as a percentage of product sales increased to 22%, primarily due to the impact of lower margin product franchises acquired with Baxalta. R&D decreased by $124 million, or 8%, as 2015 included R&D program impairment charges of $644 million, compared to $9 million in 2016, which more than offset the inclusion of Baxalta and Dyax costs, and costs related to SHP647. Non GAAP R&D increased by $403 million, or 46%, primarily due to including Baxalta and Dyax costs. Non GAAP R&D expense as a percentage of product sales decreased 2 percentage points in 2016.  Reported SG&A for 2015 has been recast to exclude amortization of acquired intangible assets, which is now presented as a separate line item in the Unaudited Consolidated Statements of Operations. SG&A increased by $1,173 million, or 64%, primarily due to the inclusion of Baxalta related costs and XIIDRA launch and promotional costs. Non GAAP SG&A increased by $1,167 million, or 68%. Non GAAP SG&A as a percentage of product sales decreased 1 percentage point. Shire recorded amortization of acquired intangible assets of $1,173 million (2015: $499 million). The increase primarily related to amortization on the intangible assets acquired with the Baxalta and Dyax transactions. In 2016, Shire recorded integration and acquisition costs of $884 million, primarily related to the Baxalta and Dyax transactions. In 2015, Shire recorded net integration and acquisition costs of $40 million, representing acquisition and integration costs of $190 million, primarily related to NPS Pharmaceuticals Inc., ViroPharma, Baxalta and Dyax. These costs were offset by a net credit of $150 million from the change in fair value of contingent consideration liabilities, primarily relating to SHP625 and SHP608. In 2016, Shire recorded reorganization costs of $121 million, primarily related to the planned closure of a facility at the Los Angeles manufacturing site acquired with Baxalta in June 2016. In 2015, Shire recorded reorganization costs of $98 million, primarily related to the relocation of roles from Pennsylvania to Massachusetts. Other expense, net increased by $443 million, primarily due to higher interest expense and amortization of one-time borrowing costs, including the write-off of certain financing costs related to the bridge facility for the Baxalta transaction. During Q3 2016, the bridge facility was fully repaid with the proceeds from the $12.1 billion public debt offering. Non GAAP Other expense, net increased by $328 million, primarily due to higher interest expense as noted above. The effective tax rate on US GAAP income in 2016 was a benefit of 26% (2015: charge of 3%) and on a Non GAAP basis was a charge of 16% (2015: charge of 16%). The effective tax rate in 2016 on US GAAP income from continuing operations is lower primarily due to the combined impact of the relative quantum of the profit before tax for the period by jurisdiction and the reversal of deferred tax liabilities (including in higher tax territories) from the Baxalta acquisition, inventory and intangible asset amortization, as well as acquisition and integration costs. The loss from discontinued operations in 2016 was $276 million, net of tax benefit of $99 million, primarily due to legal contingencies established in Q2 2016, related to the divested DERMAGRAFT business. The loss in 2015 was $34 million, net of tax, primarily related to a change in estimate for abandoned facilities charges. Selected Notes to the Unaudited US GAAP Financial Statements The share equivalents not included in the calculation of the diluted weighted average number of shares are shown below: Selected Notes to the Unaudited US GAAP Financial Statements Reconciliation of US GAAP net income to Non GAAP EBITDA and Non GAAP Operating income: Reconciliation of US GAAP product sales to Non GAAP Gross Margin: Reconciliation of US GAAP diluted earnings per ADS to Non GAAP diluted earnings per ADS: Reconciliation of US GAAP net cash provided by operating activities to Non GAAP cash generation: Reconciliation of US GAAP net cash provided by operating activities to Non GAAP free cash flow: Reconciliation of full year 2017 US GAAP diluted earnings per ADS Outlook to Non GAAP diluted earnings per ADS Outlook: Stephen Williams, Deputy Company Secretary is responsible for arranging the release of this announcement. Shire is the leading global biotechnology company focused on serving people with rare diseases and other highly specialized conditions. We strive to develop best-in-class products, many of which are available in more than 100 countries, across core therapeutic areas including Hematology, Immunology, Neuroscience, Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine / Endocrine and Hereditary Angioedema; and a growing franchise in Oncology. Our employees come to work every day with a shared mission: to develop and deliver breakthrough therapies for the hundreds of millions of people in the world affected by rare diseases and other high-need conditions, and who lack effective therapies to live their lives to the fullest. THE "SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995 Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline products, are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, the following: a further list and description of risks, uncertainties and other matters can be found in Shire's most recent Annual Report on Form 10-K and in Shire's subsequent Quarterly Reports on Form 10-Q, in each case including those risks outlined in "ITEM 1A: Risk Factors", and in subsequent reports on Form 8-K and other Securities and Exchange Commission filings, all of which are available on Shire's website. All forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Except to the extent otherwise required by applicable law, we do not undertake any obligation to update or revise forward-looking statements, whether as a result of new information, future events or otherwise. This press release contains financial measures not prepared in accordance with US GAAP. These measures are referred to as "Non GAAP" measures and include: Non GAAP operating income; Non GAAP net income; Non GAAP diluted earnings per ADS; effective tax rate on Non GAAP income before income taxes and (losses/earnings) of equity method investees (effective tax rate on Non GAAP income); Non GAAP CER; Non GAAP cost of product sales; Non GAAP gross margin; Non GAAP R&D; Non GAAP SG&A; Non GAAP other expense; Non GAAP cash generation; Non GAAP free cash flow, Non GAAP net debt, Non GAAP EBITDA and Non GAAP EBITDA margin (excluding royalties and other revenues and cost of sales related to contract manufacturing revenues). The Non GAAP measures exclude the impact of certain specified items that are highly variable, difficult to predict, and of a size that may substantially impact Shire's operations. Upfront and milestone payments related to in-licensing and acquired products that have been expensed as R&D are also excluded as specified items as they are generally uncertain and often result in a different payment and expense recognition pattern than ongoing internal R&D activities. Intangible asset amortization has been excluded from certain measures to facilitate an evaluation of current and past operating performance, particularly in terms of cash returns, and is similar to how management internally assesses performance. The Non GAAP financial measures are presented in this press release as Shire's management believes that they will provide investors with an additional analysis of Shire's results of operations, particularly in evaluating performance from one period to another. Shire's management uses Non GAAP financial measures to make operating decisions as they facilitate additional internal comparisons of Shire's performance to historical results and to competitor's results, and provides them to investors as a supplement to Shire's reported results to provide additional insight into Shire's operating performance. Shire's Remuneration Committee uses certain key Non GAAP measures when assessing the performance and compensation of employees, including Shire's executive directors. The Non GAAP financial measures used by Shire may be calculated different from, and therefore may not be comparable to, similarly titled measures used by other companies - refer to the section "Non GAAP Financial Measure Descriptions" below for additional information. In addition, these Non GAAP financial measures should not be considered in isolation as a substitute for, or as superior to, financial measures calculated in accordance with US GAAP, and Shire's financial results calculated in accordance with US GAAP and reconciliations to those financial statements should be carefully evaluated. Where applicable the following items, including their tax effect, have been excluded when calculating Non GAAP earnings and from our Non GAAP outlook: Additionally, in any given period Shire may have significant, unusual or non-recurring gains or losses which it may exclude from its Non GAAP earnings for that period. When applicable, these items would be fully disclosed and incorporated into the required reconciliations from US GAAP to Non GAAP measures. Depreciation, which is included in Cost of product sales, R&D and SG&A costs in our US GAAP results, has been separately disclosed for presentational purposes. Cash generation represents net cash provided by operating activities, excluding up-front and milestone payments for in-licensed and acquired products, tax and interest payments. Free cash flow represents net cash provided by operating activities, excluding up-front and milestone payments for in-licensed and acquired products, but including capital expenditure in the ordinary course of business. Non GAAP net debt represents cash and cash equivalents less short and long term borrowings, capital leases and other debt. A reconciliation of Non GAAP financial measures to the most directly comparable measure under US GAAP is presented on pages 22 to 24. Non GAAP CER growth is computed by restating 2016 results using average 2015 foreign exchange rates for the relevant period. Average exchange rates used by Shire for the three months ended December 31, 2016 were $1.26:£1.00 and $1.09:€1.00 (2015: $1.52:£1.00 and $1.09:€1.00). Average exchange rates used by Shire for the twelve months ended December 31, 2016 were $1.36:£1.00 and $1.11:€1.00 (2015: $1.53:£1.00 and $1.11:€1.00). We own or have rights to trademarks, service marks or trade names that we use in connection with the operation of our business. In addition, our names, logos and website names and addresses are owned by us or licensed by us. We also own or have the rights to copyrights that protect the content of our solutions. Solely for convenience, the trademarks, service marks, trade names and copyrights referred to in this press release are listed without the ©, ® and ™ symbols, but we will assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensors to these trademarks, service marks, trade names and copyrights. In addition, this press release may include trademarks, service marks or trade names of other companies. Our use or display of other parties' trademarks, service marks, trade names or products is not intended to, and does not imply a relationship with, or endorsement or sponsorship of us by, the trademark, service mark or trade name. For further information please contact:
Chogle A.,Childrens Memorial Hospital |
Sztainberg M.,Northeastern University |
Bass L.,NPS Pharmaceuticals |
Youssef N.N.,Rutgers University |
And 6 more authors.
Journal of Pediatric Gastroenterology and Nutrition | Year: 2012
Background and Aim: Chronic abdominal pain (AP) is common in children. Recall of symptoms is used clinically to determine management, to assess treatment progress, and in drug studies to assess outcomes. Limited data exist on accuracy of AP recall in children. The aim of the present study was to assess ability to accurately recall AP in children. Methods: The study was a secondary analysis of data obtained from a double-blind, randomized, placebo-controlled trial, evaluating amitriptyline in children with functional gastrointestinal disorders. Children ages 8 to 17 years with AP predominant functional gastrointestinal disorders based on Rome II criteria were recruited from 6 centers. Those with evidence of organic disease were excluded. Patients maintained AP diary daily for 1 month (presence, frequency, and intensity). At the end of the study, patients reported the number of days of AP during previous month. Agreement between daily pain reports and recalled pain was assessed. Univariate analysis was conducted with Spearman rank correlations. Results: We recruited 63 children (45 girls, mean age 12.8 years). Sixteen percent children had perfect agreement on number of days of AP. Fifty-four percent of children recalled fewer episodes of pain. The average number of days with AP by recall was 17.7/month, whereas by diary it was 23.5/month (P=0.001). Correlation between patient recall of the last week of symptoms (r=0.47) was no better than correlation between recall of the last 30 days of symptoms (r=0.48). On comparing AP recall versus various pain intensities, reported AP did not reflect only AP of greater severity. Higher correlation of recall of symptoms was seen in children 11 years or younger (r=0.59) as compared with children older than 11 years (r=0.26). Conclusions: Few children can accurately recall the episodes of AP. Children commonly recall a lower frequency of AP than that assessed by prospective diary reports. Reported recall does not reflect a shorter recollection period. Recall is not related to intensity of pain. Adolescents have worse recall of symptoms. © 2012 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Duvoisin R.M.,Oregon Health And Science University |
Pfankuch T.,Oregon Health And Science University |
Wilson J.M.,NPS Pharmaceuticals |
Grabell J.,NPS Pharmaceuticals |
And 4 more authors.
Behavioural Brain Research | Year: 2010
Metabotropic glutamate receptors (mGluRs), which are coupled to second messenger pathways via G proteins, modulate glutamatergic and GABAergic neurotransmission. Because of their role in modulating neurotransmission, mGluRs are attractive therapeutic targets for anxiety disorders. Previously we showed that mGluR8-/- male mice showed higher measures of anxiety in the open field and elevated plus maze than age-matched wild-type mice. In this study, we assessed the potential effects of acute pharmacological modulation of mGluR8 on measures of avoidable and unavoidable anxiety. In addition to wild-type mice, we also tested apolipoprotein E-deficient (Apoe-/-) mice, as these mice show increased levels of anxiety-like behaviors and therefore might show an altered sensitivity to mGluR8 stimulation. mGluR8 stimulation with the specific agonist DCPG, or modulation with AZ12216052, a new, positive allosteric modulator of mGluR8 reduced measures of anxiety in both wild-type mice. The effects of mGluR8 positive allosteric modulators, which only affect neurotransmission in the presence of extracellular glutamate, seem particularly promising for patients with anxiety disorders showing benzodiazepine insensitivity. © 2010 Elsevier B.V.
PubMed | University of Rostock, St Marks Hospital, Charité - Medical University of Berlin, NPS Pharmaceuticals and 4 more.
Type: | Journal: Clinical and translational gastroenterology | Year: 2016
In the pivotal 24-week, phase III, placebo-controlled trial, teduglutide significantly reduced parenteral support (PS) requirements in patients with short bowel syndrome (SBS). STEPS-2 was a 2-year, open-label extension of that study designed to evaluate long-term safety and efficacy of teduglutide.Enrolled patients had completed 24 weeks of either teduglutide (TED/TED) or placebo (PBO/TED) in the initial placebo-controlled study or qualified for that study, but were not treated (NT/TED) because of full enrollment. Patients received subcutaneous teduglutide 0.05mg/kg/day for up to 24 months (NT/TED and PBO/TED) or up to 30 months (TED/TED). Clinical response was defined as 20-100% reduction from baseline in weekly PS volume; baseline was considered the beginning of teduglutide treatment in the initial placebo-controlled study (TED/TED) or STEPS-2 (NT/TED and PBO/TED). Descriptive statistics summarized changes in efficacy and safety variables.Of 88 enrolled patients, 65 (74%) completed STEPS-2. The most common treatment-emergent adverse events were abdominal pain (34%), catheter sepsis (28%), and decreased weight (25%). Mean weight, body mass index, and serum albumin remained stable. In patients who completed the study, clinical response was achieved in 28/30 (93%) TED/TED, 16/29 (55%) PBO/TED, and 4/6 (67%) NT/TED patients. Mean PS volume reductions from baseline were 7.6 (66%), 3.1 (28%), and 4.0 (39%) l/week in the TED/TED, PBO/TED, and NT/TED groups, respectively. Thirteen patients achieved full enteral autonomy.In patients with SBS, long-term teduglutide treatment resulted in sustained, continued reductions in PS requirements. Overall health and nutritional status was maintained despite PS reductions.