ORLANDO, Fla., June 26 /PRNewswire-AsiaNet/ –
Data from Nearly 1,100 Patients in DURATION-1, -2 and -3 Trials Showed
Exenatide Once Weekly was Well-Tolerated
Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN), Eli Lilly and Company (NYSE: LLY) and Alkermes, Inc. (Nasdaq: ALKS) today announced results of an analysis of pooled safety data from three completed randomized controlled trials that showed the investigational product exenatide once weekly, dosed once weekly, was generally well-tolerated with a low discontinuation rate due to serious adverse events similar to pooled comparators in patients with type 2 diabetes. BYDUREON(TM) is the proposed brand name for exenatide once weekly in the United States. These findings were presented at the 70th Annual Scientific Sessions of the American Diabetes Association (ADA) in Orlando, Fla.
Safety data from the DURATION-1, -2 and -3 trials involving patients on either exenatide once weekly or pooled data from comparator groups including sitagliptin, pioglitazone HCI or insulin glargine were analyzed. The overall incidence rates of adverse events (AEs), serious AEs and discontinuations due to serious AEs were similar for exenatide once weekly versus pooled comparators. AEs occurred in 77 percent of patients receiving exenatide once weekly versus 71 percent for pooled comparators; serious AEs were 4 percent for exenatide once weekly versus 5 percent for pooled comparators; and discontinuations due to serious AEs were less than 1 percent for both groups. Discontinuation for nausea was similar in exenatide once weekly (0.7 percent) and pooled comparator (0.5 percent) cohorts. Hypoglycaemic events were lower with exenatide once weekly, and composite exposure-adjusted incidence rates were similar for exenatide once weekly versus pooled comparators for pancreatitis, gall-bladder AEs, renal impairment / dehydration and thyroid-neoplasm AEs.
In the DURATION-1, -2 and -3 studies there were no reports of severe hypersensitivity reactions, such as serious skin reactions or anaphylaxis. These data further support the known safety profile of the exenatide molecule and are consistent with the previously reported profiles of exenatide once weekly and BYETTA(R) (exenatide) injection.
“The DURATION trials not only help us understand the potential of exenatide once weekly in improving blood glucose control as measured by HbA1c, but also its safety and tolerability,” said Orville G. Kolterman, M.D., senior vice president, chief medical officer, Amylin Pharmaceuticals. “Overall, these data showed that exenatide once weekly was generally well-tolerated with a low discontinuation rate due to serious adverse events, adding to the potential of exenatide once weekly as a desirable treatment option for type 2 diabetes in just one dose per week.”
Exenatide once weekly is an investigational, extended-release medication for type 2 diabetes designed to deliver continuous therapeutic levels of exenatide in a single weekly dose. Exenatide once weekly is a once-weekly formulation of exenatide, the active ingredient in exenatide twice daily, which has been available in the U.S. since June 2005 and in Europe since 2007 and is used in more than 60 countries worldwide to improve glycaemic control in adults with type 2 diabetes. Exenatide once weekly and exenatide belong to the glucagon-like peptide-1 (GLP-1) receptor agonist class of medications.
Study Design and Findings
This analysis of the DURATION-1, -2 and -3 trials included 1,095 patients followed for 26 to 30 weeks on either exenatide once weekly (n=541) or pooled comparators (sitagliptin, pioglitizone and insulin glargine; n=554). Selected analyses compared the exenatide once weekly cohort to patients receiving exenatide in the DURATION-1 trial (n=145). Baseline demographics of cohorts were similar and were approximately 50 percent male; mean age 52-58 years; mean HbA1c 8.3-8.5 percent; and mean BMI 32-35 kg/m2.
Common treatment-emergent AEs (>/= 5 percent) that differed between exenatide once weekly and pooled comparator cohorts were injection-site pruritis and gastrointestinal (GI), including nausea, vomiting, diarrhea and constipation. The comparator-corrected incidence of nausea was 15 percent for exenatide once weekly. After three months, at which point a steady-state level of exenatide is reached, approximately 1 percent of subjects treated with exenatide once weekly reported new nausea. Other GI AEs included dyspepsia / reflux symptoms. Abdominal discomfort (2 percent) also was seen in exenatide once weekly and pooled comparator cohorts.
To further understand differences in the tolerability profile of exenatide once weekly and exenatide, the incidence of GI adverse events for the exenatide once weekly cohort was compared to that of exenatide. Nausea was reported more often by exenatide recipients (35 percent) than exenatide once weekly recipients (20 percent). Similarly, vomiting was reported by 19 percent of exenatide recipients compared with 8 percent of exenatide once weekly recipients.
Local injection-site pruritis (itchiness) (7 percent) and erythema (redness) (4 percent) were also observed with exenatide once weekly. The incidence of mild to moderate hypoglycaemic events observed with exenatide once weekly treatment (16 percent) was lower compared to the pooled comparator cohort (22 percent). There were no events of major hypoglycaemia. One death unrelated to assigned treatment was observed in each group. Composite exposure-adjusted cases (per 100 patient-years) were similar for exenatide once weekly versus pooled comparator, respectively, for pancreatitis (0.4 vs. 0.8), gall-bladder AEs (0.8 vs. 2.0), renal impairment / dehydration (1.2 vs. 1.2) and thyroid-neoplasm AEs (0.4 vs. 0.4).
It is estimated that by 2010, diabetes will affect 284.6 million adults worldwide and more than 55.4 million in Europe(i,ii). Approximately 90 to 95 percent of those are affected by type 2 diabetes, a condition characterized by failure of the pancreatic beta-cell to adequately respond to the increased demands for insulin that occur as a result of obesity-related insulin resistance(iii).
Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people(iv). In virtually every high-income country, diabetes is ranked among the leading causes of blindness, renal failure and lower limb amputation as well as one of the leading causes of death, largely because of a markedly increased risk of coronary heart disease and stroke (cardiovascular disease)(v). In the European region, estimates indicate that at least 106 billion USD will be spent on healthcare for diabetes in 2010, accounting for 28 percent of global expenditure(vi).
About exenatide Injection
Exenatide was the first approved incretin mimetic, a class of drugs for the treatment of type 2 diabetes. Exenatide exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1, secreted in response to food intake, has multiple effects on the intestine, liver, pancreas and brain that work in concert to regulate blood sugar(vii). Exenatide is approved in the European Union as adjunctive therapy to improve blood sugar control in patients with type 2 diabetes who have not achieved adequate glycaemic control on maximally tolerated doses of metformin and/or a sulfonylurea, two common oral diabetes medications. Since the U.S. market introduction in June 2005, more than one million patients worldwide have been treated with exenatide.
Important Safety Information for exenatide
In clinical studies, the most common side effects were hypoglycaemia (low blood sugar) when taken with a sulfonylurea, nausea (feeling sick), vomiting and diarrhea. For the full list of all side effects reported with exenatide, see the Package Leaflet. Exenatide should not be used in people who may be hypersensitive (allergic) to exenatide or any of the other ingredients.
About Amylin, Lilly and Alkermes
Amylin, Lilly and Alkermes are working together to develop exenatide once weekly, a subcutaneous injection of exenatide for the treatment of type 2 diabetes based on Alkermes’ proprietary Medisorb(R) technology for long-acting medications. Exenatide once weekly is not currently approved by any regulatory agencies.
Amylin Pharmaceuticals is a biopharmaceutical company dedicated to improving lives of patients through the discovery, development and commercialization of innovative medicines. Amylin’s research and development activities leverage the Company’s expertise in metabolism to develop potential therapies to treat diabetes and obesity. Amylin is headquartered in San Diego, California.
Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the industry leader in pioneering therapies to help healthcare professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients.
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Indiana, Lilly provides answers
– through medicines and information – for some of the world’s most urgent medical needs.
Alkermes, Inc. is a fully integrated biotechnology company committed to developing innovative medicines to improve patients’ lives. Alkermes’ robust pipeline includes extended-release injectable and oral products for the treatment of prevalent, chronic diseases, such as central nervous system disorders, addiction and diabetes. Headquartered in Waltham, Massachusetts, Alkermes has a research facility in Massachusetts and a commercial manufacturing facility in Ohio.
This press release contains forward-looking statements about Amylin, Lilly and Alkermes. Actual results could differ materially from those discussed or implied in this press release due to a number of risks and uncertainties, including the risk that exenatide once weekly may not be approved by the FDA or in the EU in a timely manner or at all; the companies’ response to the complete response letter may not satisfy the FDA; the FDA may request additional information prior to approval; exenatide and/or the approval of exenatide once weekly and the revenues generated from these products may be affected by competition; unexpected new data; safety and technical issues; clinical trials not being completed in a timely manner, not confirming previous results, not being predictive of real world use or not achieving the intended clinical endpoints; label expansion requests or NDA filings, such as the NDA filing for exenatide once weekly mentioned in this press release, not receiving regulatory approval; the commercial launch of exenatide once weekly being delayed; or manufacturing and supply issues. The potential for exenatide and/or exenatide once weekly may also be affected by government and commercial reimbursement and pricing decisions, the pace of market acceptance, or scientific, regulatory and other issues and risks inherent in the development and commercialization of pharmaceutical products including those inherent in the collaboration with and dependence upon Amylin, Lilly and/or Alkermes. These and additional risks and uncertainties are described more fully in Amylin’s, Lilly’s and Alkermes’ most recent SEC filings including their Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K. Amylin, Lilly and Alkermes undertake no duty to update these forward-looking statements.
BYDUREON(TM) and BYETTA(R) are trademarks of Amylin Pharmaceuticals, Inc., and Medisorb(R) is a registered trademark of Alkermes, Inc. All other marks are the marks of their respective owners.
(i) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/regional-overview. Accessed on June 9,2010.
(ii) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/europe. Accessed on June 9,2010.
(iii) Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999; 281 (21):2005-2012.
(iv) The International Diabetes Federation Diabetes Atlas. Available at http://www.diabetesatlas.org/content/what-is-diabetes. Accessed on June 9,2010.
(v) The International Diabetes Federation Diabetes Atlas. Available at http://www.diabetesatlas.org/content/what-is-diabetes. Accessed on June 9,2010.
(vi) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/europe. Accessed on June 9,2010.
(vii) Kolterman, O, Buse J, Fineman M, Gaines E, Heintz S, Bicsak T, Taylor K, Kim D, Aisporna M, Wang Y, Baron A. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting glucose in subjects with type 2 diabetes. Journal of Clinical Endocrinology & Metabolism. 2003; 88(7):3082-3089.
SOURCE: Eli Lilly and Company
CONTACT: Amylin – Anne Erickson
Lilly – Tim Coulom
Alkermes – Rebecca Peterson