Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE:
AZN) today announced results from a Phase 3 clinical study that
showed the investigational compound dapagliflozin 10 mg
demonstrated significant reductions in blood sugar levels
(glycosylated hemoglobin levels, or HbA1c) compared with placebo at
24 weeks when either agent was added to existing sitagliptin
therapy (with or without metformin) in adult patients with type 2
diabetes. The results were maintained over a 24-week extension and
similar results were observed when the data were stratified by
background therapy. The findings were presented today at the 72nd
American Diabetes Association (ADA) Scientific Sessions in
Philadelphia, PA.
The study also demonstrated significant reductions in total body
weight and fasting plasma glucose (FPG) levels in patients taking
dapagliflozin added to sitagliptin (with or without metformin),
with results maintained throughout the duration of the study
extension.
Patients were actively questioned at each study visit for signs,
symptoms or events suggestive of genital infections and urinary
tract infections. These events were more frequent with the
dapagliflozin treatment group compared to the placebo treatment
group, and were generally mild to moderate in intensity, with most
patients responding to standard treatment.
“Type 2 diabetes is a complex disease that often requires
patients to take multiple treatments to control their blood sugar
levels, with DPP4 inhibitors being some of the most widely
prescribed therapies,” said Serge Jabbour, M.D., Division Director
of Endocrinology, Thomas Jefferson University. “In this study,
dapagliflozin, in addition to diet and exercise, resulted in
reduced blood sugar levels when added to sitagliptin, a DPP4
inhibitor. These findings add to our understanding of the effect of
dapagliflozin in combination with commonly prescribed type 2
diabetes treatments.”
Dapagliflozin, an investigational oral compound, is a selective
and reversible inhibitor of sodium-glucose cotransporter 2 (SGLT2),
which works independently of insulin. Dapagliflozin is under joint
development by Bristol-Myers Squibb and AstraZeneca, and is being
investigated to evaluate its safety and efficacy in improving
glycemic control in adults with type 2 diabetes as an adjunct to
diet and exercise, for once-daily use as a monotherapy and in
combination with other glucose-lowering drugs. If approved,
dapagliflozin would potentially be the first in the new SGLT2
inhibitor class for the treatment of type 2 diabetes, a disease
where high unmet medical need exists. In a comprehensive clinical
trial program of 19 studies, dapagliflozin has been studied
together with diet and exercise as a monotherapy, and as an add-on
therapy to commonly prescribed diabetes medications, including
metformin, sulfonylurea (glimepiride), thiazolidinedione
(pioglitazone), and insulin (with or without other diabetes
therapies).
In January 2012, the U.S. Food and Drug Administration (FDA)
issued a complete response letter regarding the New Drug
Application (NDA) for dapagliflozin for the treatment of adults
with type 2 diabetes, requesting additional clinical data to allow
a better assessment of the benefit-risk profile for dapagliflozin.
In April 2012, the Committee for Medicinal Products for Human Use
(CHMP) of the European Medicines Agency (EMA) issued a positive
opinion recommending the approval of dapagliflozin for the
treatment of type 2 diabetes as an adjunct to diet and exercise, in
combination with other glucose-lowering medicinal products
including insulin, and as a monotherapy in metformin intolerant
patients. The CHMP positive opinion for dapagliflozin will now be
reviewed by the European Commission, which has the authority to
approve medicines for the European Union.
About the Study
This was a 24-week, Phase 3, multicenter, randomized,
double-blind, placebo-controlled, parallel-group study with a
24-week blinded extension. The study compared the efficacy of
dapagliflozin to placebo in patients with type 2 diabetes who are
inadequately controlled on sitagliptin monotherapy or on
sitagliptin plus metformin therapy. The primary efficacy endpoint
at 24 weeks was mean change in HbA1c from baseline for
dapagliflozin 10 mg compared to placebo, both added to sitagliptin
(with or without metformin) in adults with type 2 diabetes who had
inadequate glycemic control. The 24-week extension was designed to
assess the maintenance of efficacy with the dapagliflozin treatment
group, as well as safety and tolerability over 48 weeks.
The study included 447 adults with type 2 diabetes (aged ≥ 18
years) with inadequate glycemic control (HbA1c ≥ 7.0% and ≤ 10.0%)
who were on a stable dose of sitagliptin, a dipeptidyl peptidase-4
(DPP4) inhibitor (with or without metformin).
Patients were randomized equally to receive dapagliflozin or
placebo added to sitagliptin alone (stratum 1) or added to
sitagliptin plus metformin (stratum 2). Patients in stratum 1
received dapagliflozin 10 mg or placebo added to sitagliptin 100
mg/d. Patients in stratum 2 received dapagliflozin 10 mg or placebo
added to sitagliptin 100 mg/d plus metformin ≥ 1500 mg/d.
Study Results
Patients (n = 223) receiving dapagliflozin 10 mg added to
sitagliptin with or without metformin demonstrated significantly
greater improvements in glycemic control at the end of 24 weeks
compared to patients (n = 224) taking placebo added to sitagliptin
with or without metformin, with a change in baseline in HbA1c of
-0.48% (p-value < 0.0001, Last Observation Carried Forward
[LOCF]).
Additional results of the key primary and secondary endpoints
included the following:
- Dapagliflozin added to sitagliptin
(stratum 1) resulted in a greater reduction in HbA1c compared to
placebo added to sitagliptin, with a change in HbA1c of -0.56%
(p-value < 0.0001, LOCF).
- Dapagliflozin added to sitagliptin and
metformin (stratum 2) resulted in a greater reduction in HbA1c
compared to placebo added to sitagliptin plus metformin, with a
change in HbA1c of -0.40% (p-value < 0.0001, LOCF).
- Reductions in HbA1c were notable at
four weeks (the first recorded time point) and maintained to 48
weeks.
- Patients with a higher baseline HbA1c
(≥ 8.0%) receiving treatment with dapagliflozin achieved greater
reductions in HbA1c.
- Significant reductions in body weight
were observed with dapagliflozin compared to placebo in the entire
treatment cohort (-1.89 kg, LOCF), stratum 1 (-1.85 kg, LOCF) and
stratum 2 (-1.87 kg, LOCF), and were sustained out to 48
weeks.
- Significant differences were also
observed in adjusted mean FPG in patients who received
dapagliflozin.
Patients in the dapagliflozin group did not show a statistically
significant change from baseline in placebo subtracted seated
systolic blood pressure (SBP, baseline ≥ 130 mm Hg) compared to
placebo: -5.98 mm Hg (n = 101; dapagliflozin) vs. -5.12 mm Hg (n =
111; placebo) at week 24 (-0.86 [SE 1.47], p-value = 0.5583).
Over 24 weeks, 18.8% of patients receiving dapagliflozin
discontinued for lack of efficacy or were rescued for meeting
pre-specified rescue criteria vs. 41.5% receiving placebo.
Over the 48-week treatment period, the proportion of patients
experiencing at least one adverse event was 66.2% in the
dapagliflozin group compared to 61.1% in the placebo group. The
most common adverse events occurring in ≥ 4.0% of the study
population were as follows: nasopharyngitis, back pain, urinary
tract infection, pharyngitis, arthralgia and headache.
The proportion of patients who experienced at least one serious
adverse event was 6.7% in the dapagliflozin group compared to 8.0%
in the placebo group. In either treatment group, 3.1% discontinued
treatment due to an adverse event. Hypoglycemia was reported in
5.3% of the dapagliflozin group compared to 6.2% in the placebo
group.
The proportion of patients with diagnoses of genital infections
was 9.3% in the dapagliflozin group compared to 0.4% in the placebo
group. The proportion of patients with diagnoses of urinary tract
infections was 5.8% in the dapagliflozin group and 3.5% in the
placebo group.
Adverse events suggestive of renal impairment or failure were
observed in eight patients in the dapagliflozin group (3.6%) and
four patients in the placebo group (1.8%). In four patients in the
dapagliflozin group and in one patient in the placebo group, a
decrease in renal creatinine clearance was reported.
About Type 2 Diabetes
In 2011, diabetes was estimated to affect more than 365 million
people aged 20-79 worldwide. Because of the aging population and
the growing trend of obesity, the prevalence of diabetes is
projected to reach more than 550 million by 2030. Type 2 diabetes
accounts for approximately 90 to 95% of all cases of diagnosed
diabetes in adults. Type 2 diabetes is a chronic disease
characterized by insulin resistance and dysfunction of beta cells
in the pancreas, which decreases insulin sensitivity and secretion,
leading to elevated glucose levels. Over time, this sustained
hyperglycemia contributes to worsening insulin resistance and
further beta cell dysfunction. To date, treatments for type 2
diabetes have focused primarily on insulin-dependent mechanisms. An
approach that acts independently of insulin could provide an
additional option for adults with type 2 diabetes.
Significant unmet needs still exist, as many patients remain
inadequately controlled on their current glucose-lowering regimen.
Many patients with type 2 diabetes have additional co-morbidities
(such as obesity) which may complicate glycemic control.
About SGLT2 inhibition
The kidney plays an important role in glucose balance, normally
filtering ~180g of glucose each day, with virtually all glucose
being reabsorbed back into circulation. SGLT2 is a major
sodium-glucose cotransporter in the kidney and is an
insulin-independent pathway for the reabsorption of glucose back
into the blood.
Bristol-Myers Squibb and AstraZeneca Collaboration
Bristol-Myers Squibb and AstraZeneca entered into a
collaboration in January 2007 to enable the companies to research,
develop and commercialize select investigational drugs for type 2
diabetes. The Bristol-Myers Squibb/AstraZeneca Diabetes
collaboration is dedicated to global patient care, improving
patient outcomes and creating a new vision for the treatment of
type 2 diabetes.
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.
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical
business with a primary focus on the discovery, development and
commercialization of prescription medicines for gastrointestinal,
cardiovascular, neuroscience, respiratory and inflammation,
oncology and infectious disease. 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.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding product development. Such forward-looking statements
are based on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change
any of them, and could cause actual outcomes and results to differ
materially from current expectations. No
forward-looking statement can be guaranteed. Among other
risks, there can be no guarantee that dapagliflozin will receive
European Commission regulatory approval or, if approved, that it
will become a commercially successful product. Forward-looking
statements in this press release should be evaluated together with
the many uncertainties that affect Bristol-Myers Squibb's business,
particularly those identified in the cautionary factors discussion
in Bristol-Myers Squibb's Annual Report on Form 10-K for the year
ended December 31, 2011, in our Quarterly Reports on Form 10-Q and
our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no
obligation to publicly update any forward-looking statement,
whether as a result of new information, future events or
otherwise.
AstraZeneca Forward-Looking Statement
The statements contained herein include forward-looking
statements. Although we believe our expectations are based on
reasonable assumptions, any forward-looking statements, by their
very nature, involve risks and uncertainties and may be influenced
by factors that could cause actual outcomes and results to be
materially different from those predicted. The forward-looking
statements reflect knowledge and information available at the date
of the preparation of this press release and the Company undertakes
no obligation to update these forward-looking statements. Important
factors that could cause actual results to differ materially from
those contained in forward-looking statements, certain of which are
beyond our control, include, among other things, those risk factors
identified in the Company's Annual Report and Form 20-F Information
2011. Nothing contained herein should be construed as a profit
forecast.
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Feb 2024 to Mar 2024
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Mar 2023 to Mar 2024