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June 11, 2016 10:00 am ET

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 76^th
Scientific Sessions of the American Diabetes Association, which are
being held in New Orleans from June 10-14, 2016.

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

.

Merck Media Contacts:
Doris Li, 908-246-5701
or
Kristen Drake, 908-334-4688
or
Merck Investor Contact:
Justin Holko, 908-740-1879
or
Pfizer Media Contact:
Steve Danehy, 212-733-1538
or
Pfizer Investor Contact:
Ryan Crowe, 212-733-8160