Ertugliflozin as Add-on to Metformin or in
Initial Co-administration with Sitagliptin Showed Significant A1C
Reductions in Adults with Type 2 Diabetes
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 MET and VERTIS SITA) of
ertugliflozin, an investigational oral SGLT-2 inhibitor in
development to help improve glycemic control in adults with type 2
diabetes, met their primary endpoints. In the studies, both doses
of ertugliflozin tested (5 mg and 15 mg daily) achieved
statistically significant reductions in A1C, a measure of average
blood glucose over a two- to three-month timeframe, when added to
metformin or in initial co-administration with sitagliptin. The
results of these studies, along with 52-week extension data from
three other studies in the VERTIS clinical development program of
ertugliflozin, will be presented at the 77th Scientific Sessions of
the American Diabetes Association (ADA) in San Diego.
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“We are pleased to share these new Phase 3 data with the
scientific community that support the product profile of
ertugliflozin as add-on therapy to metformin or for first-line use
when combined with sitagliptin,” said Sam Engel, M.D., associate
vice president, Merck clinical research, cardiometabolic and
women’s health. “These studies are important milestones on our
journey to bring this medicine to adults with type 2 diabetes and
the physicians who care for them.”
“These results, combined with findings from other studies in the
VERTIS program, underscore the potential of ertugliflozin as an
important therapeutic option for adults with type 2 diabetes to
help improve their glycemic control,” said James Rusnak, M.D.,
Ph.D., chief development officer, cardiovascular and metabolic
diseases, Pfizer Global Product Development. “As the global burden
of diabetes continues to rise, we are committed to meeting
patients’ needs with additional treatment options to help manage
their condition.”
VERTIS MET, a 26-week study, evaluated the efficacy and safety
of ertugliflozin in combination with metformin, compared with
placebo and metformin, in adults with type 2 diabetes uncontrolled
on metformin monotherapy. The study showed patients taking
ertugliflozin 5 mg or 15 mg and metformin experienced greater
reductions in A1C compared to placebo (0.7 percent and 0.9 percent,
respectively, compared with 0.0 percent for placebo, p<0.001,
for both comparisons). Ertugliflozin in combination with metformin
also met a secondary endpoint in the study, as significantly more
patients taking either ertugliflozin 5 mg or 15 mg achieved the
ADA’s recommended A1C treatment goal of less than 7.0 percent
compared with placebo and metformin. As add-on therapy to
metformin, treatment with ertugliflozin also resulted in
significant reductions in fasting plasma glucose (FPG), body
weight, systolic blood pressure (SBP) and diastolic blood pressure
(DBP), compared with placebo.
The 26-week VERTIS SITA study compared the efficacy and safety
of initial combination therapy with ertugliflozin and Merck’s DPP-4
inhibitor JANUVIA® (sitagliptin) with placebo. In this study,
patients taking ertugliflozin 5 mg or 15 mg, in combination with
sitagliptin 100 mg, experienced greater reductions in A1C compared
with patients taking placebo alone (1.6 percent and 1.7 percent,
respectively, compared with 0.4 percent in patients taking placebo,
p<0.001 for both comparisons). Additionally, the
co-administration of ertugliflozin and sitagliptin met a secondary
endpoint in the study, as significantly more patients taking
ertugliflozin 5 mg or 15 mg, in combination with sitagliptin 100
mg, achieved the A1C treatment goal of less than 7.0 percent.
Treatment with the initial combination of ertugliflozin and
sitagliptin also resulted in significant reductions in FPG, body
weight and SBP, compared with placebo.
Ertugliflozin is being investigated in the VERTIS clinical
development program, which is comprised of nine Phase 3 trials in
approximately 12,600 adults with type 2 diabetes. VERTIS CV, the
ongoing cardiovascular (CV) outcomes trial of ertugliflozin,
recently completed enrollment with approximately 8,000 patients.
The primary endpoint of VERTIS CV is to assess the non-inferiority
of ertugliflozin to placebo on the composite of CV death, nonfatal
myocardial infarction or nonfatal stroke (MACE). In 2016, the trial
was expanded and pre-specified secondary endpoints were added to
test for superiority on the composite of CV death and
hospitalization for heart failure, and for superiority on CV death
alone.
Marketing applications for ertugliflozin and for two fixed-dose
combination products (ertugliflozin and JANUVIA, ertugliflozin and
metformin) are under review with the U.S. Food & Drug
Administration (FDA) and the European Medicines Agency. The
Prescription Drug User Fee Act (PDUFA) action date from the FDA is
in December 2017 for the three New Drug Applications.
Results from VERTIS MET: Ertugliflozin When Added to
Metformin Therapy (1168-P)
In this randomized, double-blind 26-week investigational
multicenter study, 621 patients with type 2 diabetes and a baseline
A1C of 7.0 – 10.5 percent, who were inadequately controlled with
metformin monotherapy (greater or equal to 1,500 mg/day for more
than or equal to 8 weeks), were randomized to receive placebo,
ertugliflozin 5 mg/day or ertugliflozin 15 mg/day in a 1:1:1 ratio,
as an add-on therapy to metformin. In addition to meeting the
study’s primary endpoint of improved blood glucose control at 26
weeks, ertugliflozin in combination with metformin also met a key
secondary endpoint in the study, as significantly more patients
taking ertugliflozin 5 mg and 15 mg in combination with metformin
achieved the ADA’s recommended A1C treatment goal of less than 7.0
percent (35.3 percent and 40.0 percent, respectively) compared with
placebo and metformin (15.8 percent) (p<0.001, for both
comparisons based on adjusted odds ratio comparisons). The
following statistically significant placebo-adjusted reductions
were observed for the primary and additional key secondary
endpoints for ertugliflozin added to metformin:
- A1C: 0.7 percent (5 mg) and 0.9 percent
(15 mg) (p<0.001 for both comparisons);
- FPG: 26.7 mg/dL (5 mg) and 38.3 mg/dL
(15 mg) (p<0.001 for both comparisons);
- Body weight: 3.7 lbs (1.7 kg) (5 mg)
and 3.5 lbs (1.6 kg) (15 mg) (p<0.001 for both
comparisons);
- SBP: 3.7 mmHg (5 mg) (p=0.002) and 4.5
mmHg (15 mg) (p<0.001); and
- DBP: 1.8 mmHg (5 mg) (p=0.013) and 2.4
mmHg (15 mg) (p=0.001).
The incidence of adverse events was 42.5 percent, 50.2 percent
and 45.0 percent in the ertugliflozin 5 mg and metformin,
ertugliflozin 15 mg and metformin, and placebo and metformin
groups, respectively. A higher incidence of genital mycotic
infections in females was observed in patients taking ertugliflozin
5 mg (5.5 percent) and 15 mg (6.3 percent) versus placebo (0.9
percent) (p=0.032 for 15 mg) and in males (3.1 percent (5 mg); 3.2
percent (15 mg); 0.0 percent (placebo)), added to metformin.
Ertugliflozin had no adverse impact on bone mineral density at week
26 (95 percent CI). Symptomatic urinary tract infections,
hypoglycemia and hypovolemia adverse events were similar between
treatment groups.
Results from VERTIS SITA: Initial Combination of
Ertugliflozin and JANUVIA® (sitagliptin)
(1197-P)
In this 26-week, randomized, double-blind investigational
multicenter Phase 3 study of 291 patients with an A1C of 8.0 – 10.5
percent inadequately controlled with diet and exercise, patients
were randomized to ertugliflozin 5 mg and sitagliptin 100 mg,
ertugliflozin 15 mg and sitagliptin 100 mg or placebo. The study
met its primary endpoint of improved blood glucose control at 26
weeks with A1C reductions of 1.6 percent (ertugliflozin 5 mg and
sitagliptin 100 mg), 1.7 percent (ertugliflozin 15 mg and
sitagliptin 100 mg), compared with 0.4 percent in patients taking
placebo (p<0.001 for both comparisons). In addition, the study
met a key secondary endpoint, with significantly more patients
taking ertugliflozin 5 mg or 15 mg in combination with sitagliptin
100 mg achieving the A1C treatment goal of less than 7.0 percent
(35.7 percent and 31.3 percent, respectively) compared with placebo
(8.3 percent) (p<0.001, for both comparisons based on adjusted
odds ratio comparisons).
The following statistically significant placebo-adjusted
reductions were observed for the primary and additional key
secondary endpoints:
- A1C: 1.2 percent (ertugliflozin 5 mg
and sitagliptin 100 mg) and 1.2 percent (ertugliflozin 15 mg and
sitagliptin 100 mg) (p<0.001 for both comparisons);
- FPG: 38.9 mg/dL for 5 mg ertugliflozin
and 100 mg sitagliptin, 46.1 mg/dL for 15 mg ertugliflozin and 100
mg sitagliptin) (p<0.001 for both comparisons);
- 2-hour PMG: 62.4 mg/dL for
ertugliflozin 5 mg and 100 mg sitagliptin and 69.6 mg/dL for
ertugliflozin 15 mg and 100 mg sitagliptin (p<0.001 for both
comparisons);
- Body weight: 4.4 lbs (2.0 kg) for
ertugliflozin 5 mg and sitagliptin 100 mg and 4.6 lbs (2.1 kg) for
ertugliflozin 15 mg and sitagliptin 100 mg (p<0.001 for both
comparisons);
- SBP: 4.4 mmHg for ertugliflozin 5 mg
and sitagliptin 100 mg (p=0.011) and 6.4 mmHg for ertugliflozin 15
mg and sitagliptin 100 mg (p<0.001).
Observed reductions in DBP were not significant (p>0.05). The
incidence of adverse events was 44.9 percent, 44.8 percent and 42.3
percent in the ertugliflozin 5 mg and sitagliptin 100 mg,
ertugliflozin 15 mg and sitagliptin 100 mg, and placebo groups,
respectively. A higher incidence of genital mycotic infections in
males was observed in patients taking ertugliflozin 5 mg (5.3
percent) and 15 mg (1.9 percent) versus placebo (0.0 percent) and
in females (4.9 percent (5 mg); 7.0 percent (15 mg); 5.0 percent
(placebo)) (p≥0.05 for all comparisons). Incidence rates of urinary
tract infections, symptomatic hypoglycemia and hypovolemia were low
and not significantly different across groups.
Important Information about JANUVIA®
(sitagliptin) 25 mg, 50 mg and 100 mg tablets
JANUVIA (sitagliptin) 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®
(sitagliptin)
JANUVIA is contraindicated in patients with a history of a
serious hypersensitivity reaction to sitagliptin, such as
anaphylaxis or angioedema.
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
(sitagliptin), 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.
Postmarketing cases of bullous pemphigoid requiring
hospitalization have been reported with DPP-4 inhibitor use. In
reported cases, patients typically recovered with topical or
systemic immunosuppressive treatment and discontinuation of the
DPP-4 inhibitor. Tell patients to report development of blisters or
erosions while receiving JANUVIA. If bullous pemphigoid is
suspected, JANUVIA should be discontinued and referral to a
dermatologist should be considered for diagnosis and appropriate
treatment.
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 more than a century, Merck, a leading global
biopharmaceutical company known as MSD outside of the United States
and Canada, has been inventing for life, bringing forward medicines
and vaccines for many of the world’s most challenging diseases.
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. Today,
Merck continues to be at the forefront of research to advance the
prevention and treatment of diseases that threaten people and
communities around the world - including cancer, cardio-metabolic
diseases, emerging animal diseases, Alzheimer’s disease and
infectious diseases including HIV and Ebola. For more information,
visit www.merck.com and connect with us
on Twitter, Facebook, Instagram, YouTube
and LinkedIn.
About Pfizer Inc.: Working together for a healthier
world®
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 health care
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, we have worked to make a difference for
all who rely on us. We routinely post information that may be
important to investors on our website at www.pfizer.com. In
addition, to learn more, please visit us on www.pfizer.com and
follow us on Twitter at @Pfizer and @PfizerNews, 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 2016
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 10,
2017. 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, and applications submitted to the
FDA and the EMA for monotherapy and fixed-dose combinations,
including their 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 other jurisdictions; whether and
when the FDA and EMA may approve the pending applications and
whether and when regulatory authorities in any other jurisdictions
may approve any such other 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 in
monotherapy or in fixed-dose combination; and competitive
developments. The competitive landscape for type 2 diabetes
therapies, including SGLT2 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, 2016 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 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, 908-246-5701Kristen Drake,
908-334-4688orPfizer Media Contact:Steve Danehy,
212-733-1538orMerck Investor Contact:Amy Klug, 908-740-1898orPfizer
Investor Contact:Ryan Crowe, 212-733-8160
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