Exenatide tQT Study Showed No Prolongation of QT Interval

SAN DIEGO, INDIANAPOLIS, and WALTHAM, Mass., July 7, 2011 /PRNewswire/ — Amylin
Pharmaceuticals, Inc. (Nasdaq: AMLN), Eli Lilly and Company (NYSE: LLY) and
Alkermes, Inc. (Nasdaq: ALKS) today announced results from a thorough QT (tQT)
study that assessed the potential of exenatide to increase the QT interval
across a wide range of plasma concentrations. The study was conducted to satisfy
a requirement by the U.S. Food and Drug Administration (FDA) in support of the
New Drug Application (NDA) for BYDUREON(TM) (exenatide extended-release for
injectable suspension), an investigational medication for type 2 diabetes. Using
multiple heart rate correction methodologies, the study met the pre-specified
primary endpoint, demonstrating that exenatide at and above therapeutic levels
did not prolong the corrected QT (QTc) interval in healthy individuals. Further,
the study found no relationship between QTc interval and plasma exenatide
concentrations.

The QT interval represents the amount of time the heart’s electrical system
takes to repolarize, or recharge, after each beat (i). As prolongation of the QT
interval may increase the risk for cardiac arrhythmias, the FDA requires a tQT
study for most new drugs in development. A tQT study is a specialized clinical
trial designed to assess whether an investigational medication has the potential
to prolong the QT interval.

“The findings of this tQT study are clear. Exenatide did not lead to QT
prolongation, even at very high concentrations in the blood,” said Christian
Weyer, M.D., senior vice president, research and development, Amylin
Pharmaceuticals. “This study was designed in accordance with existing guidelines
and in consultation with the FDA. We are confident in these results and will
continue to work toward making BYDUREON available to patients in the U.S. as
soon as possible.”

In its October 2010 complete response letter, the FDA requested a tQT study with
exposures of exenatide at higher than typical therapeutic levels of BYDUREON,
such as those that might be achieved in patients with impaired renal function.
The companies plan to submit results of the tQT study to the FDA in the third
quarter of 2011 as part of their reply to the complete response letter for the
BYDUREON NDA.

Study Details

This randomized double-blind study, designed in accordance with the FDA’s
published guidance on clinical evaluation of QT/QTc interval (ICH E14), compared
the effects of exenatide at or above therapeutic concentrations to placebo on
the QT interval in approximately 75 healthy volunteers. The primary endpoint was
to determine whether exenatide administered at therapeutic and supratherapeutic
concentrations differed from placebo in the mean change in the QTc interval
(defined as the upper bound of the 95 percent confidence interval for
placebo-corrected, baseline subtracted QTc being <10 milliseconds). All heart
rate correction methodologies that satisfied the pre-specified selection
criteria, including QTcP, QTcF and QTcI, met the primary endpoint. Moxifloxacin,
an antibiotic known to prolong the QT interval, was used as a positive control.
The companies plan to present the full data set at a major medical meeting and
submit the data for publication.

BYDUREON is the proposed brand name for exenatide extended-release for
injectable suspension. It is an investigational medication for type 2 diabetes
designed to deliver continuous therapeutic levels of exenatide in a single
weekly dose. BYDUREON is a once-weekly formulation of exenatide, the active
ingredient in BYETTA® (exenatide) injection, which has been available in the
U.S. since June 2005 and is used in more than 70 countries worldwide to improve
glycemic control in adults with type 2 diabetes. BYDUREON received marketing
authorization in the European Union in June 2011.

About Diabetes

Diabetes affects nearly 36 million people in the U.S. and an estimated 347
million adults worldwide (ii). Approximately 90-95 percent of those affected
have type 2 diabetes. Diabetes costs more than $174 billion per year in direct
and indirect medical expenses (iii).

According to the Centers for Disease Control and Prevention's National Health
and Nutrition Examination Survey, approximately 60 percent of people with
diabetes do not achieve their target blood sugar levels with their current
treatment regimen (iv). In addition, 85 percent of type 2 diabetes patients are
overweight and 55 percent are considered obese (v). Data indicate that weight
loss (even a modest amount) supports patients in their efforts to achieve and
sustain glycemic control. (vi, vii)

About BYETTA® (exenatide) injection

BYETTA was the first glucagon-like peptide-1 (GLP-1) receptor agonist to be
approved by the FDA for the treatment of type 2 diabetes. BYETTA exhibits many
of the same effects as the human incretin hormone GLP-1. GLP-1 improves blood
sugar after food intake through multiple effects that work in concert on the
stomach, liver, pancreas and brain.

BYETTA is an injectable prescription medicine that may improve blood sugar
(glucose) control in adults with type 2 diabetes mellitus, when used with a diet
and exercise program. BYETTA is not insulin and should not be taken instead of
insulin. BYETTA is not currently recommended to be taken with insulin. BYETTA is
not for people with type 1 diabetes or people with diabetic ketoacidosis. BYETTA
has not been studied in people who have pancreatitis.

BYETTA provides sustained A1C control and low incidence of hypoglycemia when
used alone or in combination with metformin or a thiazolidinedione, with
potential weight loss (BYETTA is not a weight-loss product). BYETTA was approved
in the U.S. in April 2005 and in Europe in November 2006 and has been used by
more than 1.8 million patients since its introduction. See important safety
information below. Additional information about BYETTA is available at
www.BYETTA.com.

Important Safety Information for BYETTA® (exenatide) injection

Based on postmarketing data, BYETTA has been associated with acute pancreatitis,
including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. Patients
should be observed for signs and symptoms of pancreatitis after initiation or
dose escalation of BYETTA. The risk for getting low blood sugar is higher if
BYETTA is taken with another medicine that can cause low blood sugar, such as a
sulfonylurea. BYETTA should not be used in people who have severe kidney
problems and should be used with caution in people who have had a kidney
transplant. Patients should talk with their healthcare provider if they have
severe problems with their stomach, such as delayed emptying of the stomach
(gastroparesis) or problems with digesting food. Antibodies may develop with use
of BYETTA. Patients who develop high titers to exenatide could have worsening or
failure to achieve adequate glycemic control. Consider alternative therapy if
this occurs. Severe allergic reactions can happen with BYETTA. There have been
no clinical studies establishing conclusive evidence of macrovascular risk
reduction with BYETTA or any other antidiabetic drug.

The most common side effects with BYETTA include nausea, vomiting, diarrhea,
dizziness, headache, feeling jittery, and acid stomach. Nausea most commonly
happens when first starting BYETTA, but may become less over time.

These are not all the side effects from use of BYETTA. A healthcare provider
should be consulted about any side effect that is bothersome or does not go
away.

For additional important safetyinformation about BYETTA, please see the full
Prescribing Information (www.byetta.com/pi) and Medication Guide
(www.byetta.com/mg).

About Amylin, Lilly and Alkermes

Amylin and Lilly partnered to develop and market BYDUREON, which is based on
proprietary technology for long-acting medications developed by Alkermes, Inc.
BYDUREON is approved in the EU and is under regulatory review in the U.S.

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 and has a commercial
manufacturing facility in Ohio.

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, 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, Mass., 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 the tQT study results mentioned in this press release may not be
predictive; BYDUREON may not be approved by the FDA as soon as anticipated or at
all; the companies' response to the FDA's complete response letter may not be
submitted in the third quarter of 2011 and/or the information provided in such
response may not satisfy the FDA; the FDA may request additional information
prior to approval; BYETTA and/or the approval of BYDUREON 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 not receiving regulatory approval; the commercial launch
of BYDUREON being delayed; or manufacturing and supply issues. The potential for
BYETTA and/or BYDUREON 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®are trademarks of Amylin Pharmaceuticals, Inc. All other
marks are the marks of their respective owners.

P-LLY

(i) Long QT Syndrome. Heart Rhythm Society. Available at:

http://www.hrsonline.org/PatientInfo/HeartRhythmDisorders/IDisorders/index.cfm.

Accessed July 7, 2011.

(ii) Danaei G, et al. National, regional, and global trends in fasting plasma
glucose and diabetes prevalence since 1980: systematic analysis of health
examination surveys and epidemiological studies with 370 country-years and 2.7
million participants. Lancet. 2011;DOI:10.1016/S0140-6736(11)60679-X.

(iii) Direct and Indirect Costs of Diabetes in the United States. American
Diabetes Association. Available at:

http://www.diabetes.org/how-to-help/action/resources/cost-of-diabetes.html.

Accessed July 7, 2011.

(iv) Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular
disease among adults with previously diagnosed diabetes. JAMA. 2004;291:335-42.

(v) Bays HE, Chapman RH, Grandy S. The relationship of body mass index to
diabetes mellitus, hypertension and dyslipidaemia: comparison of data from two
national surveys. Int J Clin Pract. 2007;61:737-47.

(vi) Nutrition Recommendations and Interventions for Diabetes: a position
statement of the American Diabetes Association. Diabetes Care. 2008;31 Suppl
1;S61-78.

(vii) Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in
type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr.
2003;22:331-9.

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SOURCE Amylin Pharmaceuticals, Inc.; Eli Lilly and Company; Alkermes, Inc.