MEDIA RELEASE PR40201
Exenatide Once Weekly Safety and Tolerability Pooled Summary Data Presented at ADA 2010
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).
About Diabetes
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:
2010.
(ii) The International Diabetes Federation Diabetes Atlas. Available at:
(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
2010.
(v) The International Diabetes Federation Diabetes Atlas. Available at
2010.
(vi) The International Diabetes Federation Diabetes Atlas. Available at:
(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
Phone: +1-858-754-4443
Cell: +1-858-349-3195
Email: anne.erickson@amylin.com
Lilly - Tim Coulom
Phone: +1-317-655-2998
Cell: +1-317-544-9757
Email: coulomtd@lilly.com
Alkermes - Rebecca Peterson
Phone: +1-781-609-6378
Cell: +1-617-899-2447
Email: rebecca.peterson@alkermes.com
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