In clinical trials, new once-daily Farxiga, in addition to diet and exercise, improved glycemic control by removing glucose from the body
AstraZeneca
(NYSE:AZN) and Bristol-Myers
Squibb Company (NYSE:BMY) announced the U.S. Food and Drug
Administration (FDA) approved Farxiga™
[far-SEE-ga] (dapagliflozin), a once-daily oral treatment indicated as
an adjunct to diet and exercise to improve glycemic control in adults
with type 2 diabetes mellitus. Farxiga should not be used for the
treatment of patients with type 1 diabetes or diabetic ketoacidosis.
The recommended starting dose of Farxiga is 5 mg once daily,
taken in the morning, with or without food. In patients tolerating Farxiga
5 mg once daily who require additional glycemic control, the dose can be
increased to 10 mg once daily. Farxiga is part of a newer class
of medicines called sodium-glucose cotransporter 2 (SGLT2) inhibitors,
which remove glucose via the kidneys.
“With the diabetes epidemic escalating and many people with type 2
diabetes struggling to reach their blood sugar goals, Farxiga
offers an important new option for healthcare professionals and adult
patients,” said Brian Daniels, senior vice president, global development
and medical affairs, Bristol-Myers Squibb. “In clinical trials, Farxiga
helped improve glycemic control, and offered additional benefits of
weight and blood pressure reductions.”
Farxiga is contraindicated in patients with a history of a
serious hypersensitivity reaction to Farxiga or with severe renal
impairment, end stage renal disease, or patients on dialysis.
“The addition of Farxiga to our U.S. treatment portfolio is a
step forward as we work to help reduce the burden of type 2 diabetes by
offering a range of treatment options with different modes of action,”
said Briggs Morrison, M.D., executive vice president, Global Medicines
Development and chief medical officer, AstraZeneca. “We aim to help
adults with type 2 diabetes, and their doctors, create individualized
treatment programs that will help patients lower their glucose levels.”
Dapagliflozin (marketed outside of the United States as Forxiga®)
is approved for the treatment of adults with type 2 diabetes, along with
diet and exercise, in 40 countries, including European Union countries
and Australia.
Farxiga Clinical Development Program
The robust Farxiga clinical development program included 24
clinical studies evaluating safety and efficacy. The studies included
more than 11,000 adults with type 2 diabetes, including more than 6,000
patients treated with Farxiga.
Farxiga causes intravascular volume contraction. Symptomatic
hypotension can occur after initiating Farxiga particularly in
patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2),
elderly patients, or patients on loop diuretics. Before initiating Farxiga
in patients with one or more of these characteristics, volume status
should be assessed and corrected. Monitor for signs and symptoms of
hypotension after initiating therapy. Farxiga increases serum
creatinine and decreases eGFR. Elderly patients and patients with
impaired renal function may be more susceptible to these changes.
Adverse reactions related to renal function can occur after initiating Farxiga.
Renal function should be evaluated prior to initiation of Farxiga
and monitored periodically thereafter.
In a 24-week, add-on to metformin clinical trial, adult patients with
type 2 diabetes treated with Farxiga 5 mg (n=137; baseline HbA1c
8.2%) or 10 mg (n=135; baseline A1c 7.9%) had significant reductions in
HbA1c of -0.7% and -0.8%, respectively, compared with placebo plus
metformin reductions of -0.3% (n=137; baseline HbA1c 8.1%). In the same
study, the placebo-adjusted reduction in body weight was -2.2 kg with Farxiga
5 mg (baseline 84.7 kg) and -2.0 kg with 10 mg (baseline 86.3 kg). Also,
mean changes from baseline in systolic blood pressure relative to
placebo plus metformin were -4.5 mmHg and -5.3 mmHg with Farxiga
5 mg or 10 mg plus metformin, respectively. No major episodes of
hypoglycemia were seen in any of the treatment arms. Minor episodes of
hypoglycemia were reported in 1.5%, 0.7%, and 0% with Farxiga 5
mg, 10 mg, and placebo plus metformin, respectively.
In addition to the clinical development program, the
AstraZeneca/Bristol-Myers Squibb Diabetes Alliance has initiated
DECLARE, a large, randomized, placebo-controlled study of more than
17,000 adult patients with type 2 diabetes designed to determine the
effect of Farxiga, when added to the patients’ current
anti-diabetes therapy, on the risk of CV events, such as CV death,
myocardial infarction or ischemic stroke, compared with placebo. The
study, which will also provide additional data on the long-term safety
profile, initiated enrollment in April 2013 and has an anticipated
completion date of 2019.
INDICATION AND LIMITATION OF USE FOR FARXIGA™ (dapagliflozin)
Farxiga is indicated as an adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes mellitus.
Farxiga is not recommended for patients with type 1 diabetes
mellitus or for the treatment of diabetic ketoacidosis.
IMPORTANT SAFETY INFORMATION FOR FARXIGA
Contraindications
• History of a serious hypersensitivity reaction to Farxiga
• Severe renal impairment, end stage renal disease, or patients on
dialysis
Warnings and Precautions
• Hypotension: Farxiga causes intravascular volume
contraction. Symptomatic hypotension can occur after initiating Farxiga,
particularly in patients with impaired renal function (eGFR <60
mL/min/1.73 m2), elderly patients, or patients on loop
diuretics. Before initiating Farxiga in patients with one or more
of these characteristics, assess and correct volume status. After
initiating therapy, monitor for signs and symptoms of hypotension.
• Impairment in Renal Function: Farxiga increases serum
creatinine and decreases eGFR. Elderly patients and patients with
impaired renal function may be more susceptible to these changes.
Adverse reactions related to renal function can occur after initiating Farxiga.
Before initiating Farxiga, evaluate renal function and monitor
periodically thereafter. Discontinue Farxiga when eGFR is
persistently <60 mL/min/1.73 m2.
• Hypoglycemia with Concomitant Use with Insulin and Insulin
Secretagogues: Insulin and insulin secretagogues are known to cause
hypoglycemia. Farxiga can increase the risk of hypoglycemia when
combined with these agents. Consider a lower dose of insulin or the
insulin secretagogue to reduce the risk of hypoglycemia when used in
combination with Farxiga.
• Genital Mycotic Infections: Farxiga increases the risk
of genital mycotic infections. Patients with a history of genital
mycotic infections were more likely to develop genital mycotic
infections. Monitor and treat appropriately.
• Increases in Low-Density Lipoprotein Cholesterol (LDL-C): Increases
in LDL-C occur with Farxiga. After initiating Farxiga,
monitor LDL-C and treat per standard of care.
• Bladder cancer: Across 22 clinical studies, newly diagnosed
cases of bladder cancer were reported in 0.17% of Farxiga
-treated patients and 0.03% of placebo/comparator-treated patients.
After excluding patients in whom exposure to study drug was <1 year at
the time of diagnosis of bladder cancer, there were 4 cases with Farxiga
and no cases with placebo/comparator. Bladder cancer risk factors and
hematuria (a potential indicator of pre-existing tumors) were balanced
between treatment arms at baseline. There were too few cases to
determine whether the emergence of these events is related to Farxiga.
There are insufficient data to determine whether Farxiga has an
effect on pre-existing bladder tumors. Farxiga should not be used
in patients with active bladder cancer. Use with caution in patients
with a prior history of bladder cancer.
Macrovascular Outcomes: There have been no clinical studies
establishing conclusive evidence of macrovascular risk reduction with Farxiga
or any other antidiabetic drug.
Adverse Reactions
• In a pool of 12 placebo-controlled studies, the most common adverse
reactions (≥5%) treated with Farxiga 5 mg, 10 mg, and placebo
respectively were female genital mycotic infections (8.4% vs 6.9% vs
1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract
infections (5.7% vs 4.3% vs 3.7%).
Use in Specific Populations
• Pregnant Women: There are no adequate and well-controlled
studies of Farxiga in pregnant women. Consider appropriate
alternative therapies, especially during the second and third trimesters.
• Nursing Mothers: It is not known whether Farxiga is
excreted in human milk. Because of the potential for serious adverse
reactions in nursing infants from Farxiga, discontinue nursing or
discontinue Farxiga.
• Geriatric Use: A higher proportion of patients ≥65 years
treated with Farxiga had adverse reactions related to volume
depletion and renal impairment or failure compared to patients treated
with placebo. No Farxiga dose change is recommended based on age.
Please click here
for US Full Prescribing Information and Medication Guide for Farxiga.
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 glucose-lowering regimen.
About SGLT2 Inhibition
The kidney plays a contributing role in maintaining normal glucose
balance, in part by filtering and subsequently reabsorbing glucose back
into circulation. SGLT2, a sodium-glucose cotransporter found
predominantly in the kidney, is responsible for the majority of glucose
reabsorption. Selective inhibition of SGLT2 reduces the reabsorption of
glucose and enables its removal via the urine, which is associated with
reductions in HbA1c, weight and systolic blood pressure.
About the AstraZeneca/Bristol-Myers Squibb Diabetes Alliance
Dedicated to addressing the global burden of diabetes by advancing
individualized patient care, AstraZeneca and Bristol-Myers Squibb are
working in collaboration to develop and commercialize a versatile
portfolio of innovative treatment options for diabetes and related
metabolic disorders that aim to provide treatment effects beyond glucose
control. Find out more about the Alliance and our commitment to meeting
the needs of health care professionals and people with diabetes at www.astrazeneca.com
or www.bms.com.
On December 19, 2013 AstraZeneca and Bristol-Myers Squibb announced an
agreement under which AstraZeneca will acquire the entirety of
Bristol-Myers Squibb’s interests in the companies’ diabetes alliance to
consolidate worldwide ownership of the diabetes business within
AstraZeneca. The closing of the transactions contemplated by the
agreement is subject to customary terms and conditions, and is expected
to occur during the first quarter of 2014.
About AstraZeneca
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.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission
is to discover, develop and deliver innovative medicines that help
patients prevail over serious diseases. For more information about
Bristol-Myers Squibb, visit www.bms.com
or follow us on Twitter at http://twitter.com/bmsnews.

Media:Bristol-Myers SquibbKen Dominski, 609-252-5251ken.dominski@bms.comorAstraZenecaKristin Rogers, 302-885-8922kristin.rogers@astrazeneca.comorInvestors:Bristol-Myers SquibbRanya Dajani, 609-252-5330ranya.dajani@bms.comorRyan Asay, 609-252-5020ryan.asay@bms.comorAstraZenecaKarl Hard, 44-20-7604-8123karl.j.hard@astrazeneca.comorAnthony Brown, 44-20-7604-8067Anthony.brown@astrazeneca.comorJens Lindberg, 44-20-7604-8414jens.lindberg@astrazeneca.comorColleen Proctor, 302-886-1842colleen.proctor@astrazeneca.com