Ongoing CV Outcomes Trial of Ertugliflozin
Expanded to Test for Superiority in CV Risk
Reduction
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, in partnership with Pfizer Inc. (NYSE:PFE), today announced
that two Phase 3 studies (VERTIS Mono and VERTIS Factorial) of
ertugliflozin, an investigational oral SGLT-2 inhibitor for the
treatment of patients with type 2 diabetes, met their primary
endpoints. The study results showed statistically significant
reductions in A1C (a measure of average blood glucose) for both
ertugliflozin doses tested (5 mg and 15 mg daily). These results
from the VERTIS clinical development program of ertugliflozin will
be presented for the first time at the 76th Scientific Sessions of
the American Diabetes Association, which are being held in New
Orleans from June 10-14, 2016.
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A 26-week investigational study (VERTIS Mono), which evaluated
ertugliflozin as monotherapy, met its primary endpoint, showing
that patients randomized to ertugliflozin 5 mg and 15 mg had
significantly greater A1C reductions of 0.99 percent and 1.16
percent, respectively, compared with placebo (p<0.001, for both
comparisons). In addition, significantly more patients taking
ertugliflozin 5 mg and 15 mg achieved the A1C treatment goal of
less than 7.0 percent (28.2 percent and 35.8 percent, respectively)
compared with placebo (13.1 percent) (p<0.001, for both
comparisons), which was a secondary endpoint of the study.
VERTIS Factorial, another 26-week investigational study,
evaluated the co-administration of ertugliflozin and Merck’s DPP-4
inhibitor JANUVIA® (sitagliptin). This study also met its primary
endpoint, with greater reductions in A1C observed in patients
taking ertugliflozin in combination with sitagliptin compared to
ertugliflozin or sitagliptin alone. An A1C reduction of 1.5 percent
was observed in both combinations studied (ertugliflozin 5 mg or 15
mg with sitagliptin 100 mg), as compared with A1C reductions of 1.0
percent with ertugliflozin 5 mg alone, 1.1 percent with
ertugliflozin 15 mg alone, and 1.1 percent with sitagliptin 100 mg
alone (p<0.001 for both combinations vs. individual
treatments).
In addition, the co-administration of ertugliflozin and
sitagliptin was significantly more effective than ertugliflozin or
sitagliptin alone in achieving the A1C treatment goal of less than
7.0 percent, which was a secondary endpoint of the study.
Specifically, 52.3 percent of patients taking ertugliflozin 5 mg in
combination with sitagliptin 100 mg and 49.2 percent of patients
taking ertugliflozin 15 mg in combination with sitagliptin 100 mg
reached an A1C goal of less than 7.0 percent. In comparison, 26.4
percent achieved this A1C goal with ertugliflozin 5 mg, 31.9
percent with ertugliflozin 15 mg, and 32.8 percent with sitagliptin
100 mg (p<0.001 for both combinations vs. individual treatments
in model-based tests).
Indications and Usage for JANUVIA®
(sitagliptin) 25 mg, 50 mg and 100 mg tablets
JANUVIA is indicated as an adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes mellitus.
JANUVIA should not be used in patients with type 1 diabetes or for
the treatment of diabetic ketoacidosis. JANUVIA has not been
studied in patients with a history of pancreatitis. It is unknown
whether patients with a history of pancreatitis are at increased
risk of developing pancreatitis while taking JANUVIA.
Selected Important Risk Information about
JANUVIA®
JANUVIA is contraindicated in patients with a history of a
serious hypersensitivity reaction to sitagliptin, such as
anaphylaxis or angioedema.
Update on VERTIS Clinical Development Program
VERTIS CV, a randomized, double-blind, placebo-controlled,
parallel-group trial, was recently expanded to enable testing for
superiority in improving CV outcomes in type 2 diabetes patients.
The study is now targeting enrollment of approximately 8,000
patients with type 2 diabetes and established vascular disease.
Pre-specified secondary endpoints were added to test for
superiority on the composite of CV death and hospitalization for
heart failure and superiority on CV death alone. The primary
endpoint of the trial continues to be to assess the non-inferiority
of ertugliflozin versus placebo on the composite of CV death,
nonfatal myocardial infarction or nonfatal stroke (MACE).
“Merck’s goal in our diabetes development program is to evaluate
new treatment options to advance the care of people with type 2
diabetes around the world,” said Peter Stein, M.D., vice president,
late stage development, diabetes and endocrinology, Merck. “We are
encouraged that these first Phase 3 studies of investigational
ertugliflozin met their primary endpoints for ertugliflozin as a
monotherapy and in combination with sitagliptin, and we look
forward to progressing the VERTIS clinical development program with
Pfizer.”
“Pfizer has a legacy in CV disease, and after discovering
ertugliflozin, wanted a partner that could help us meet our goal to
improve disease management in patients with type 2 diabetes,” said
James Rusnak, M.D., Ph.D., chief development officer,
cardiovascular & metabolics, Pfizer Global Product Development.
“Diabetes is a progressive disease, and many patients need multiple
treatment options to manage their condition.”
Merck and Pfizer plan to submit New Drug Applications to the
U.S. Food and Drug Administration for ertugliflozin and the two
fixed-dose combination tablets (ertugliflozin plus JANUVIA, and
ertugliflozin plus metformin) by the end of 2016. VERTIS Mono and
VERTIS Factorial are a part of the VERTIS clinical development
program comprised of a total of nine Phase 3 trials in
approximately 12,600 adults with type 2 diabetes. Results from the
other seven VERTIS trials will be submitted for publication and
presentation at future scientific congresses.
Results from VERTIS Mono: Ertugliflozin as a Monotherapy
(130-LB)
In this randomized, double-blind, placebo-controlled
investigational study, 461 patients with type 2 diabetes and a
baseline A1C of 7.0 – 10.5 percent, inclusive, who were
inadequately controlled on diet and exercise alone and who had an
eGFR (estimated glomerular filtration rate) of ≥55 mL/min/1.73m2,
were randomized to receive ertugliflozin 5 mg, ertugliflozin 15 mg,
or placebo in a 1:1:1 ratio. In addition to meeting the primary
endpoint of improved blood glucose control at 26 weeks and the
secondary endpoint of achieving an A1C treatment goal of less than
7.0 percent, the following observations were made on additional
secondary endpoints:
- Placebo-adjusted mean significant
reduction in body weight of 3.9 lbs (1.76 kg) (5 mg) and 4.8 lbs
(2.16 kg) (15 mg) (p<0.001, for both comparisons);
- Placebo-adjusted mean significant
reductions in fasting plasma glucose (FPG) of 34.50 mg/dL (5 mg)
and 44.01 mg/dL (15 mg) (p<0.001, for both comparisons);
- Placebo-adjusted mean significant
reductions in postprandial glucose (PPG) of 69.03 md/dL (5 mg) and
67.33 mg/dL (15 mg) (p<0.001, for both comparisons); and
- Numerically greater reductions in
systolic blood pressure (3.31 mmHg (5 mg), 1.71 mmHg (15 mg)) and
diastolic blood pressure (1.80 mmHg (5 mg), 0.37 mmHg (15 mg)),
which did not reach statistical significance, for both
comparisons.
Overall adverse event (AE) rates were similar between
ertugliflozin 5 mg (52.6 percent), ertugliflozin 15 mg (55.9
percent) and placebo (52.3 percent), with a similar rate of one or
more serious AEs across all groups (4.5 percent for ertugliflozin 5
mg; 1.3 percent for ertugliflozin 15 mg; 1.3 percent for placebo).
The rates of discontinuations due to AEs were low across all groups
(2.6 percent for ertugliflozin 5 mg; 2.0 percent for ertugliflozin
15 mg; 3.3 percent for placebo). A higher incidence of genital
mycotic infections in females was observed in patients taking
ertugliflozin 15 mg (22.6 percent) and ertugliflozin 5 mg (16.4
percent) compared with placebo (5.6 percent). There was no increase
in the incidence of urinary tract infections with either dose of
ertugliflozin relative to placebo.
Results from VERTIS Factorial: Ertugliflozin When Combined
with JANUVIA (Sitagliptin) (125-LB)
In the randomized, double-blind investigational study, 1,233
patients with type 2 diabetes with a baseline A1C of 7.5 – 11.0
percent who were inadequately controlled on metformin alone (≥1500
mg/day) and who had an eGFR (estimated glomerular filtration rate)
of ≥60 mL/min/1.73m2, were randomized to one of five treatment
groups in a 1:1:1:1:1 ratio: co-administration of ertugliflozin 5
mg with sitagliptin 100 mg; co-administration of ertugliflozin 15
mg with sitagliptin 100 mg; ertugliflozin 5 mg; ertugliflozin 15
mg; or sitagliptin 100 mg.
In addition to meeting the primary endpoint of improved blood
glucose control at 26 weeks and the secondary endpoint of achieving
an A1C treatment goal of less than 7.0 percent, the study also
showed that the co-administration of ertugliflozin and sitagliptin
was significantly more effective than ertugliflozin or sitagliptin
alone in reducing FPG, and significantly more effective in reducing
body weight and systolic blood pressure compared to sitagliptin
alone, which were secondary endpoints. The following results on
these secondary endpoints were observed:
- Patients taking ertugliflozin 5 mg and
sitagliptin 100 mg experienced a reduction in FPG of 44.0 mg/dL
(p≤0.004 vs. ertugliflozin 5 mg and p<0.001 vs. sitagliptin);
48.7 mg/dL with ertugliflozin 15 mg and sitagliptin 100 mg
(p<0.001 vs. each individual treatment); 35.7 mg/dL with
ertugliflozin 5 mg; 36.9 mg/dL with ertugliflozin 15 mg; and 25.6
mg/dL with sitagliptin 100 mg.
- The co-administration of ertugliflozin
5 mg and sitagliptin 100 mg resulted in a reduction in body weight
of 5.5 lbs (2.5 kg); 6.4 lbs (2.9 kg) with ertugliflozin 15 mg and
sitagliptin 100 mg; and 1.5 lbs (0.7 kg) with sitagliptin 100 mg
(p<0.001 for both combinations vs. sitagliptin). Patients taking
ertugliflozin alone, 5 or 15 mg, also experienced a reduction in
body weight of 5.9 lbs (2.7 kg) and 8.1 lbs (3.7 kg),
respectively.
- Patients taking ertugliflozin 5 mg and
sitagliptin 100 mg also experienced a reduction in systolic blood
pressure of 3.4 mmHg (p=0.005 vs. sitagliptin); 3.7 mmHg with
ertugliflozin 15 mg and sitagliptin 100 mg (p=0.002 vs.
sitagliptin); and 0.7 mmHg with sitagliptin 100 mg. Patients taking
ertugliflozin 5 or 15 mg alone also experienced a reduction in
systolic blood pressure of 3.9 and 3.7 mmHg, respectively.
The incidence of AEs was similar across all therapeutic groups
in the study (51.2 percent for ertugliflozin 5 mg; 43.1 percent for
ertugliflozin 15 mg; 41.7 percent for sitagliptin 100 mg; 45.7
percent for ertugliflozin 5 mg plus sitagliptin 100 mg; 46.7
percent for ertugliflozin 15 mg plus sitagliptin 100 mg). The rates
of serious AEs were similar across all groups (3.2 percent for
ertugliflozin 5 mg; 1.2 percent for ertugliflozin 15 mg; 1.6
percent for sitagliptin 100 mg; 2.5 percent for ertugliflozin 5 mg
plus sitagliptin 100 mg; 1.6 percent for ertugliflozin 15 mg plus
sitagliptin 100 mg). The rates of discontinuations due to AEs were
similar across the five treatment arms (2.4 percent for
ertugliflozin 5 mg; 1.2 percent for ertugliflozin 15 mg; 0.4
percent for sitagliptin 100 mg; 1.2 percent for ertugliflozin 5 mg
plus sitagliptin 100 mg; 2.9 percent for ertugliflozin 15 mg plus
sitagliptin 100 mg).
The incidence of genital mycotic infections was higher in
patients receiving ertugliflozin compared to sitagliptin alone
(females, 4.9-7.6 percent vs. 1.1 percent, and males, 2.4-4.7
percent vs. 0 percent).
Selected Important Risk Information about JANUVIA®
continued
There have been postmarketing reports of acute pancreatitis,
including fatal and nonfatal hemorrhagic or necrotizing
pancreatitis, in patients taking JANUVIA. After initiating JANUVIA,
observe patients carefully for signs and symptoms of pancreatitis.
If pancreatitis is suspected, promptly discontinue JANUVIA and
initiate appropriate management. It is unknown whether patients
with a history of pancreatitis are at increased risk of developing
pancreatitis while taking JANUVIA.
Assessment of renal function is recommended prior to initiating
JANUVIA and periodically thereafter. A dosage adjustment is
recommended in patients with moderate or severe renal insufficiency
and in patients with end-stage renal disease requiring hemodialysis
or peritoneal dialysis. Caution should be used to ensure that the
correct dose of JANUVIA is prescribed.
There have been postmarketing reports of worsening renal
function, including acute renal failure, sometimes requiring
dialysis. A subset of these reports involved patients with renal
insufficiency, some of whom were prescribed inappropriate doses of
sitagliptin.
When JANUVIA was used in combination with a sulfonylurea or
insulin, medications known to cause hypoglycemia, the incidence of
hypoglycemia was increased over that of placebo. Therefore, a lower
dose of sulfonylurea or insulin may be required to reduce the risk
of hypoglycemia.
The incidence (and rate) of hypoglycemia based on all reports of
symptomatic hypoglycemia were: 12.2% (0.59 episodes/patient-year)
for JANUVIA 100 mg in combination with glimepiride (with or without
metformin), 1.8% (0.24 episodes/patient-year) for placebo in
combination with glimepiride (with or without metformin), 15.5%
(1.06 episodes/patient-year) for JANUVIA 100 mg in combination with
insulin (with or without metformin), and 7.8% (0.51
episodes/patient-year) for placebo in combination with insulin
(with or without metformin).
There have been postmarketing reports of serious
hypersensitivity reactions in patients treated with JANUVIA, such
as anaphylaxis, angioedema, and exfoliative skin conditions
including Stevens-Johnson syndrome. Onset of these reactions
occurred within the first 3 months after initiation of treatment
with JANUVIA, with some reports occurring after the first dose. If
a hypersensitivity reaction is suspected, discontinue JANUVIA,
assess for other potential causes for the event, and institute
alternative treatment for diabetes.
Angioedema has also been reported with other dipeptidyl
peptidase-4 (DPP-4) inhibitors. Use caution in a patient with a
history of angioedema with another DPP-4 inhibitor because it is
unknown whether such patients will be predisposed to angioedema
with JANUVIA®.
There have been postmarketing reports of severe and disabling
arthralgia in patients taking DPP-4 inhibitors. The time to onset
of symptoms following initiation of drug therapy varied from 1 day
to years. Patients experienced relief of symptoms upon
discontinuation of the medication. A subset of patients experienced
a recurrence of symptoms when restarting the same drug or a
different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible
cause for severe joint pain and discontinue drug if
appropriate.
There have been no clinical studies establishing conclusive
evidence of macrovascular risk reduction with JANUVIA or with any
other antidiabetic drug.
In clinical studies, the adverse reactions reported, regardless
of investigator assessment of causality, in ≥5% of patients treated
with JANUVIA as monotherapy and in combination therapy and more
commonly than in patients treated with placebo, were upper
respiratory tract infection, nasopharyngitis, and headache.
About Merck
For 125 years, Merck has been a global health care leader
working to help the world be well. Merck is known as MSD outside
the United States and Canada. Through our prescription medicines,
vaccines, biologic therapies, and animal health products, we work
with customers and operate in more than 140 countries to deliver
innovative health solutions. We also demonstrate our commitment to
increasing access to health care through far-reaching policies,
programs and partnerships. For more information, visit
www.merck.com and connect with us on Twitter, Facebook, YouTube and
LinkedIn.
About Pfizer Inc.
At Pfizer, we apply science and our global resources to bring
therapies to people that extend and significantly improve their
lives. We strive to set the standard for quality, safety and value
in the discovery, development and manufacture of healthcare
products. Our global portfolio includes medicines and vaccines as
well as many of the world’s best-known consumer health care
products. Every day, Pfizer colleagues work across developed and
emerging markets to advance wellness, prevention, treatments and
cures that challenge the most feared diseases of our time.
Consistent with our responsibility as one of the world’s premier
innovative biopharmaceutical companies, we collaborate with health
care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world.
For more than 150 years, Pfizer has worked to make a difference for
all who rely on us. For more information, please visit us
at www.pfizer.com. In addition, to learn more, follow us on
Twitter @Pfizer and @Pfizer_News, LinkedIn
, YouTube and like us on Facebook at Facebook.com/Pfizer.
Forward-Looking Statement of Merck & Co., Inc.,
Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J.,
USA (the “company”) includes “forward-looking statements” within
the meaning of the safe harbor provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These statements are
based upon the current beliefs and expectations of the company’s
management and are subject to significant risks and uncertainties.
There can be no guarantees with respect to pipeline products that
the products will receive the necessary regulatory approvals or
that they will prove to be commercially successful. If underlying
assumptions prove inaccurate or risks or uncertainties materialize,
actual results may differ materially from those set forth in the
forward-looking statements.
Risks and uncertainties include but are not limited to, general
industry conditions and competition; general economic factors,
including interest rate and currency exchange rate fluctuations;
the impact of pharmaceutical industry regulation and health care
legislation in the United States and internationally; global trends
toward health care cost containment; technological advances, new
products and patents attained by competitors; challenges inherent
in new product development, including obtaining regulatory
approval; the company’s ability to accurately predict future market
conditions; manufacturing difficulties or delays; financial
instability of international economies and sovereign risk;
dependence on the effectiveness of the company’s patents and other
protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory
actions.
The company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause
results to differ materially from those described in the
forward-looking statements can be found in the company’s 2015
Annual Report on Form 10-K and the company’s other filings with the
Securities and Exchange Commission (SEC) available at the SEC’s
Internet site (www.sec.gov).
Pfizer Disclosure Notice
The information contained in this release is as of June 11,
2016. Pfizer assumes no obligation to update forward-looking
statements contained in this release as the result of new
information or future events or developments.
This release contains forward-looking information about a
product candidate, ertugliflozin, including its potential benefits,
that involves substantial risks and uncertainties that could cause
actual results to differ materially from those expressed or implied
by such statements. Risks and uncertainties include, among other
things, the uncertainties inherent in research and development,
including the ability to meet anticipated trial commencement and
completion dates and regulatory submission dates, as well as the
possibility of unfavorable clinical trial results, including
unfavorable new clinical data and additional analyses of existing
clinical data; whether and when any applications for ertugliflozin
may be filed with regulatory authorities in any jurisdictions;
whether and when regulatory authorities in any jurisdictions may
approve such applications, which will depend on the assessment by
such regulatory authorities of the benefit-risk profile suggested
by the totality of the efficacy and safety information submitted;
decisions by regulatory authorities regarding labeling and other
matters that could affect the availability or commercial potential
of ertugliflozin; and competitive developments. The competitive
landscape for type 2 diabetes therapies, including SGLT
2-inhibitors, continues to evolve. The success of our ertugliflozin
program is dependent on developments in that space.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended
December 31, 2015 and in its subsequent reports on Form 10-Q,
including in the sections thereof captioned “Risk Factors” and
“Forward-Looking Information and Factors That May Affect Future
Results”, as well as in its subsequent reports on Form 8-K, all of
which are filed with the U.S. Securities and Exchange Commission
and available at www.sec.gov(link is
external) and www.pfizer.com.
# # #
Please see Prescribing Information for JANUVIA®
(sitagliptin) at
http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_pi.pdf
and Medication Guide for JANUVIA at
http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_mg.pdf.
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Merck Media Contacts:Doris Li, 908-246-5701orKristen Drake,
908-334-4688orMerck Investor Contact:Justin Holko,
908-740-1879orPfizer Media Contact:Steve Danehy,
212-733-1538orPfizer Investor Contact:Ryan Crowe, 212-733-8160
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