Exenatide Once Weekly Safety And Tolerability Pooled Summary Data Presented At Ada 2010

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27th June 2010, 03:23am - Views: 1142

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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,


    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


    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:


    (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


    (v) The International Diabetes Federation Diabetes Atlas. Available at


    (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;



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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