|[March 03, 2014]
U.S. FDA Approves Bydureon® Pen (exenatide extended-release for injectable suspension) for Once-Weekly Treatment of Adults with Type 2 Diabetes
WILMINGTON, Del. --(Business Wire)--
today announced that the U.S. Food and Drug Administration (FDA) has
approved the Bydureon® Pen (exenatide extended-release
for injectable suspension) 2 mg as an adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes. Bydureon
should not be used for treatment of patients with type 1 diabetes or
diabetic ketoacidosis. Bydureon is not recommended as first-line
therapy for patients who have inadequate glycemic control on diet and
exercise. Bydureon is not a substitute for insulin. The
concurrent use of Bydureon with insulin has not been studied and
is not recommended.
Bydureon is the first and only once-weekly medicine for adults
with type 2 diabetes. The Bydureon Pen is a pre-filled,
single-use pen injector, eliminating the need for the patient to
transfer the medication between a vial and syringe during the
self-injection process. The Bydureon Pen contains the same
formulation and dose as the original Bydureon single-dose tray,
providing the same continuous release of exenatide. Bydureon has
been shown to provide powerful HbA1c (blood glucose level) reduction. In
a 24-week, randomized, open-label trial, once-weekly Bydureon demonstrated
an HbA1c reduction of 1.6 percentage points vs 0.9 percentage points for
twice-daily Byetta® (exenatide) injection at 24 weeks
(baseline HbA1c 8.5% and 8.4%, respectively). Additionally, Bydureon
demonstrated a mean weight reduction of 5.1 pounds (2.3 kg) vs 3.1
pounds (1.4 kg) with Byetta (baseline 213.8 pounds [97 kg] and
207.2 pounds [94 kg], respectively). Bydureon is not indicated
for the management of obesity, and weight change was a secondary
endpoint in clinical trials.
The Prescribing Information for Bydureon includes a Boxed Warning
regarding the risk of thyroid C-cell tumors. It is unknown whether Bydureon
causes thyroid C-cell tumors, including medullary thyroid carcinoma
(MTC), in humans, as human relevance could not be determined by clinical
or nonclinical studies. Bydureon is contraindicated in patients
with a personal or family history of MTC, in patients with Multiple
Endocrine Neoplasia syndrome type 2 (MEN 2), or history of a serious
hypersensitivity reaction to exenatide.
Based on post-marketing data, exenatide has been associated with acute
pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing
pancreatitis. If pancreatitis is suspected, Bydureon should be
discontinued promptly and not restarted if pancreatitis is confirmed.
Other antidiabetic therapies should be considered in patients with a
history of pancreatitis. Bydureon and Byetta contain the
same active ingredient and should not be used together.
"We are pleased to receive approval for the Bydureon Pen, which
can provide a powerful reduction in blood glucose levels along with the
potential benefit of weight loss, through a once-weekly dose in a
pre-filled device," said Briggs Morrison, M.D., executive vice
president, Global Medicines Development and chief medical officer,
AstraZeneca. "We are committed to addressing the needs of adults with
type 2 diabetes, including ongoing research to develop new treatments
and methods of delivery."
The Bydureon Pen delivers exenatide via microsphere technology in
a once-weekly dose requiring no titration. It can be administered at any
time of the day, with or without meals. Prior to initiation of the Bydureon
Pen, patients should be trained by their healthcare professional.
AstraZeneca plans to make the Bydureon Pen available for patients
later this year. The Bydureon single-dose tray will remain on the
market for patients prescribed Bydureon.
About Bydureon® Clinical Development
The FDA approval of Bydureon was based on the safety and efficacy
data from the pivotal DURATION-5 clinical trial, in which treatment with Bydureon
resulted in improvements in glycemic control. The DURATION-5 trial was a
randomized open-label clinical study of 252 adult patients with type 2
diabetes and inadequate glycemic control with diet and exercise alone or
with oral antidiabetic therapy, including metformin, a sulfonylurea, a
thiazolidinedione, or a combination of two of these oral type 2 diabetes
medications comparing Bydureon to Byetta (n = 129 and n =
123, respectively). After 24 weeks of treatment, patients taking
once-weekly Bydureon experienced a statistically significant mean
reduction in HbA1c of 1.6 percentage points (8.5% baseline), compared to
a reduction of 0.9 percentage points (8.4% baseline) for patients taking Byetta.
HbA1c is a measure of average blood sugar over three months. Both
treatment groups achieved a reduction in weight by the end of the study,
with an average loss of 5.1 pounds or 2.3 kg (213.8 pounds or 97 kg
baseline) for patients taking Bydureon and 3.1 pounds or 1.4 kg
(207.2 pounds or 94 kg baseline) for patients taking Byetta
(change in weight was a secondary endpoint). The most
frequently reported adverse event in both groups was nausea, reported
less frequently by Bydureon users (14%) than by Byetta
users (35%). Other common treatment-emergent adverse events in the Bydureon
group included diarrhea (9.3% vs 4.1%) and injection-site erythema (5.4%
vs 2.4%, respectively). There were no major hypoglycemic events in
either treatment arm. Minor episodes of hypoglycemia occurred
in Bydureon 2 mg and Byetta 10 mcg patients with
concomitant sulfonylurea use (12.5% vs 11.8%, respectively).
The FDA approval for Bydureon >was received in 2012. Bydureon
is currently available in 42 countries worldwide, including European
INDICATION and IMPORTANT SAFETY INFORMATION for
extended-release for injectable suspension)
Indication and Important Limitations of Use for BYDUREON:
BYDUREON is indicated as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus.
• Because of the uncertain relevance of the rat thyroid C-cell tumor
findings to humans, prescribe only to patients for whom potential
benefits are considered to outweigh potential risk.
• Not recommended as first-line therapy for patients who have inadequate
glycemic control on diet and exercise.
• Not a substitute for insulin, should not be used in patients with type
1 diabetes or diabetic ketoacidosis, and cannot be recommended for use
• BYDUREON and BYETTA® (exenatide) injection
both contain the same active ingredient, exenatide, and should not be
• Exenatide has been associated with acute pancreatitis, including fatal
and non-fatal hemorrhagic or necrotizing pancreatitis, based on
postmarketing data. It is unknown whether patients with a history of
pancreatitis are at increased risk for pancreatitis while using
BYDUREON; consider other antidiabetic therapies for these patients.
Important Safety Information for BYDUREON:
BOXED WARNING: RISK OF THYROID C-CELL TUMORS
Exenatide extended-release causes an increased incidence in thyroid
C-cell tumors at clinically relevant exposures in rats compared to
controls. It is unknown whether BYDUREON causes thyroid C-cell tumors,
including medullary thyroid carcinoma (MTC), in humans, as human
relevance could not be determined by clinical or nonclinical studies.
BYDUREON is contraindicated in patients with a personal or family
history of MTC and in patients with Multiple Endocrine Neoplasia
syndrome type 2 (MEN 2). Routine serum calcitonin or thyroid ultrasound
monitoring is of uncertain value in patients treated with BYDUREON.
Patients should be counseled regarding the risk and symptoms of thyroid
Patients with a personal or family history of MTC and in patients with
Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
Patients with prior serious hypersensitivity reactions to exenatide or
to any of the product components.
Warnings and Precautions
Pancreatitis: Based on postmarketing data, exenatide has been
associated with acute pancreatitis, including fatal and non-fatal
hemorrhagic or necrotizing pancreatitis. After initiation of BYDUREON,
observe patients carefully for pancreatitis (persistent severe
abdominal pain, sometimes radiating to the back, with or without
vomiting). If pancreatitis is suspected, BYDUREON should be
discontinued promptly and should not be restarted if pancreatitis is
Hypoglycemia: Increased risk of hypoglycemia when used in
combination with a sulfonylurea (SFU). Clinicians may consider
reducing the SFU dose to minimize risk of hypoglycemia. It is possible
that use of BYDUREON with other glucose-independent insulin
secretagogues (eg, meglitinides) could increase the risk of
Renal Impairment: Should not be used in patients with severe
renal impairment or end-stage renal disease. Use with caution in
patients with renal transplantation or moderate renal failure.
Postmarketing reports of altered renal function with exenatide,
including increased serum creatinine, renal impairment, worsened
chronic renal failure, and acute renal failure, sometimes requiring
hemodialysis and kidney transplantation.
Gastrointestinal Disease: Because exenatide is commonly
associated with gastrointestinal adverse reactions, BYDUREON is not
recommended in patients with severe gastrointestinal disease (eg,
Immunogenicity: Patients may develop antibodies to exenatide.
In 5 registration trials, attenuated glycemic response was associated
in 6% of BYDUREON-treated patients with antibody formation. If
worsening of or failure to achieve adequate glycemic control occurs,
consider alternative antidiabetic therapy.
Hypersensitivity: Postmarketing reports of serious
hypersensitivity reactions (eg, anaphylaxis and angioedema). If this
occurs, patients should discontinue BYDUREON and other suspect
medications and promptly seek medical advice.
Macrovascular Outcomes: No clinical studies establishing
conclusive evidence of macrovascular risk reduction with BYDUREON or
any other antidiabetic drug.
In 5 comparator-controlled, 24- to 30-week BYDUREON trials, the
incidence of withdrawal due to adverse events was 4.9% for BYDUREON,
4.9% for BYETTA, and 2.0% for other comparators. The most common
adverse reactions leading to withdrawal for BYDUREON, BYETTA, and
comparators respectively were nausea (0.5%, 1.5%, 0.3%),
injection-site nodule (0.5%, 0.0%, 0.0%), diarrhea (0.3%, 0.4%, 0.3%),
injection-site reaction (0.2%, 0.0%, 0.0%), and headache (0.2%, 0.0%,
0.0%). One percent of BYDUREON patients withdrew due to injection-site
Most Common Adverse Reactions (=5%)
BYDUREON vs BYETTA:
24-week trial: nausea (14% vs 35%), diarrhea (9.3% vs
4.1%), injection-site erythema (5.4% vs 2.4%).
30-week trial: nausea (27% vs 33.8%), diarrhea (16.2% vs
12.4%), vomiting (10.8% vs 18.6%), injection-site pruritus (18.2%
vs 1.4%), constipation (10.1% vs 6.2%), gastroenteritis viral
(8.8% vs 5.5%), gastroesophageal reflux disease (7.4% vs 4.1%),
dyspepsia (7.4% vs 2.1%), injection-site erythema (7.4% vs 0.0%),
fatigue (6.1% vs 3.4%), headache (6.1% vs 4.8%), injection-site
hematoma (5.4% vs 11.0%).
BYDUREON vs titrated insulin glargine: nausea (12.9% vs 1.3%),
headache (9.9% vs 7.6%), diarrhea (9.4% vs 4.0%), injection-site
nodule (6.0% vs 0.0%).
Combination trial vs sitagliptin and pioglitazone: nausea
(24.4% vs 9.6% and 4.8%), diarrhea (20.0% vs 9.6% and 7.3%), vomiting
(11.3% vs 2.4% and 3.0%), headache (9.4% vs 9.0% and 5.5%),
constipation (6.3% vs 3.6% and 1.2%), fatigue (5.6% vs 0.6% and 3.0%),
dyspepsia (5.0% vs 3.6% and 2.4%), decreased appetite (5.0% vs 1.2%
and 0.0%), injection-site pruritus (5.0% vs 4.8% and 1.2%).
Monotherapy trial vs sitagliptin, pioglitazone, and metformin:
nausea (11.3% vs 3.7%, 4.3%, and 6.9%), diarrhea (10.9% vs 5.5%, 3.7%,
and 12.6%), injection-site nodule (10.5% vs 6.7%, 3.7%, and 10.2%),
constipation (8.5% vs 2.5%, 1.8%, and 3.3%), headache (8.1% vs 9.2%,
8.0%, and 12.2%), dyspepsia (7.3% vs 1.8%, 4.9%, and 3.3%).
Hypoglycemia: No major hypoglycemia was reported for BYDUREON-
or comparator-treated patients in five 24- to 30-week trials. Minor
hypoglycemia incidences for BYDUREON vs comparator-treated patients
were as follows: 24-week trial vs BYETTA: with SFU, 12.5% vs 11.8%;
without SFU, 0.0% for both; 30-week trial vs BYETTA: with SFU, 14.5%
vs 15.4%; without SFU, 0.0% vs 1.1%; monotherapy trial vs sitagliptin,
pioglitazone, and metformin: 2.0% vs 0.0% (all comparators);
combination trial vs sitagliptin and pioglitazone: 1.3% vs 3.0% and
1.2%; vs titrated insulin glargine, with SFU, 20.0% vs 43.9%; without
SFU, 3.7% vs 19.1%.
Injection-site reactions were observed more frequently in
BYDUREON-treated patients (17.1%) vs patients treated with BYETTA
(12.7%), titrated insulin glargine (1.8%), or placebo injection
(6.4%-13.0%). Injection-site reactions were observed in 14.2% of
antibody-positive patients vs 3.1% of antibody-negative patients, with
higher incidence in those with higher-titer antibodies. BYETTA-treated
patients had similar incidence between antibody-positive and
antibody-negative patients (5.8% vs 7.0%). Small, asymptomatic,
subcutaneous injection-site nodules are seen with the use of BYDUREON.
Oral Medications: BYDUREON slows gastric emptying and can
reduce the rate of absorption of orally administered drugs. Use with
caution with oral medications.
Warfarin: Postmarketing reports with exenatide of increased
international normalized ratio (INR) sometimes associated with
bleeding with concomitant use of warfarin. Monitor INR frequently
until stable upon initiation or alteration of BYDUREON.
Use in Specific Populations
Pregnant and Nursing Women: Based on animal data, BYDUREON may
cause fetal harm and should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus. To report
drug exposure during pregnancy call 1-800-633-9081. When administered
to a nursing woman, a decision should be made whether to discontinue
nursing or to discontinue BYDUREON.
Pediatric Patients: Use in pediatric patients is not
recommended as safety and effectiveness have not been established.
here for US Full Prescribing Information for BYDUREON (exenatide
extended-release for injectable suspension) 2 mg, including Boxed
WARNING regarding risk of thyroid C-cell tumors, and click
here for Medication Guide.
About GLP-1 Receptor Agonists
An agonist is a molecule, such as a drug or a hormone, which binds to a
receptor of a cell and triggers a response by that cell. A glucagon-like
peptide-1 (GLP-1) receptor agonist binds to and activates the GLP-1
receptor, which exhibits multiple anti-hyperglycemic actions.
About Type 2 Diabetes
Diabetes is estimated to affect 25.8 million people in the U.S. and more
than 382 million people worldwide. The prevalence of diabetes is
projected to reach more than 592 million people worldwide by 2035. Type
2 diabetes accounts for approximately 90-95 percent of all cases of
diagnosed diabetes. Type 2 diabetes is a chronic disease
characterized by pathophysiologic defects leading to elevated glucose
levels. Over time, this sustained hyperglycemia contributes to further
progression of the disease. Significant unmet needs still exist, as many
patients remain inadequately controlled on their current
AstraZeneca is a global, innovation-driven biopharmaceutical business
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of cardiovascular,
metabolic, respiratory, inflammation, autoimmune, oncology, infection
and neuroscience diseases. AstraZeneca operates in over 100 countries
and its innovative medicines are used by millions of patients worldwide.
For more information please visit: www.astrazeneca.com.
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