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February 26, 2017 12:30 pm ET

Letermovir Prophylaxis Associated with Lower All-Cause Mortality Through Week 24 Post-Transplant

Company Plans to Submit New Drug Applications for Letermovir in U.S. and EU in 2017

Merck & Co., Inc. (NYSE:MRK), known as MSD outside the United States and
Canada, today announced results of the pivotal Phase 3 clinical study of
letermovir, an investigational antiviral medicine for the prevention of
clinically-significant cytomegalovirus (CMV) infection in adult (18
years and older) CMV-seropositive recipients of an allogeneic
hematopoietic stem cell transplant (HSCT), also known as bone marrow
transplant (BMT). The study met its primary efficacy endpoint, showing
that significantly fewer patients with undetectable CMV DNA at the start
of study treatment developed clinically significant CMV infection
through Week 24 post-HSCT (using a non-complete equals failure approach,
in which patients who discontinued from the study prior to Week 24
post-transplant or had a missing outcome at Week 24 post-transplant were
counted as failures). In the study, letermovir prophylaxis was
associated with lower all-cause mortality through Week 24 post-HSCT.
Based on these results, Merck plans to submit regulatory applications
for the approval of letermovir in the United States and European Union
(EU) in 2017.

Results from the study were presented for the first time at the BMT
Tandem Meetings, the combined annual meetings of the Center for
International Blood & Marrow Transplant Research (CIBMTR) and the
American Society for Blood and Marrow Transplantation (ASBMT), in
Orlando, Fla., Feb. 22-26.

“These results showed that letermovir prophylaxis beginning after HSCT
and continuing through Day 100 post-transplant significantly reduced CMV
infection requiring preemptive antiviral therapy through Week 24
post-transplant,” said Dr. Francisco M. Marty, associate professor of
medicine at Harvard Medical School and attending physician in transplant
and oncology infectious diseases at Dana-Farber Cancer Institute and
Brigham and Women’s Hospital, who presented the data. “In this study,
letermovir was associated with lower all-cause mortality. Based on these
findings, letermovir as primary prophylaxis of CMV infection represents
a potential new strategy for the prevention of CMV in this high-risk
patient population.”

CMV is the most common clinically significant viral infection in
allogeneic HSCT recipients. HSCT is a medical procedure in the field of
hematologic oncology, most often performed for the treatment of patients
with certain cancers of the blood or bone marrow, such as leukemia and
lymphoma. While preemptive therapy (treatment when CMV DNA is detected
in the blood) with antiviral medicines can reduce the incidence of CMV
disease, CMV reactivation post-HSCT is associated with higher mortality
despite the use of preemptive therapy.

“There is an unmet need for therapeutic options in the prevention of CMV
infection in hematopoietic stem cell transplant recipients,” said Dr.
Nicholas Kartsonis, vice president, infectious disease clinical
research, Merck Research Laboratories. “As part of Merck’s long-standing
commitment to developing innovative approaches in the fight against
infectious diseases, we look forward to submitting regulatory
applications for letermovir this year.”

About the pivotal Phase 3 study

CMV seropositive HSCT recipients 18 years or older who had undetectable
plasma CMV DNA within 5 days of randomization were eligible for the
study. Patients were randomized in a 2:1 ratio to receive either
letermovir or placebo administered once daily, either in oral tablet or
intravenous formulation, through Week 14 (Day 100) post-HSCT. Letermovir
was dosed at 480 mg/day (or 240 mg/day if the patient was on the
immunosuppressant medication cyclosporine). Letermovir was started after
HSCT; as early as on the day of transplant and no later than 28 days
post-transplant. Patients were assessed weekly through Week 14 and
biweekly through Week 24 for the primary efficacy endpoint of clinical
significant CMV infection. Patients who developed clinically significant
CMV infection, defined as the onset of CMV disease or initiation of
anti-CMV preemptive therapy based on documented viremia (as measured by
the central laboratory) and the clinical condition of the patient,
discontinued study drug and received anti-CMV preemptive therapy.
Patients continued to be followed for safety every other month through
Week 48 post-HSCT.

The primary endpoint of the study was the proportion of patients with
clinically significant CMV infection through Week 24 post-HSCT among
patients with undetectable CMV DNA at the start of study treatment.
Patients who discontinued the study early for any reason or who had
missing data at Week 24 post-HSCT were considered study failures. All
adverse events were analyzed through 14 days after the last dose of
study drug.

The study met its primary efficacy endpoint, showing that of 495 treated
patients who had undetectable CMV DNA at the start of study treatment,
significantly fewer patients developed clinically significant CMV
infection in the letermovir arm (37.5%, n=122/325) compared to the
placebo arm (60.6%, n=103/170) through Week 24 post-HSCT [treatment
difference: -23.5 (95% confidence interval -32.5 to -14.6), one-sided
p<0.0001].

Efficacy was consistently demonstrated across patient subgroups.
Letermovir demonstrated significant benefit compared to placebo in time
to clinically significant CMV infection through Week 24 post-HSCT in
both patients at higher risk and lower risk for CMV disease at baseline
(log-rank two-sided p<0.0001 for both groups).

In addition, a secondary endpoint evaluating the end-of-treatment period
(at Week 14 post-HSCT) showed that significantly fewer patients
developed clinically significant CMV infection in the letermovir arm
(19.1%, n=62/325) compared to the placebo arm (50.0%, n=85/170) through
Week 14 (Day 100) post-HSCT [treatment difference: -31.3 (95% confidence
interval -39.9 to -22.6), one-sided p<0.0001].

In this study, letermovir was associated with lower all-cause mortality
through Week 24 post-HSCT (9.8%, n=32/325) compared to placebo (15.9%,
n=27/170), log-rank two-sided p=0.0317.

The most common adverse events of any severity reported for the
letermovir and placebo arms, respectively, were: graft-versus-host
disease (GVHD) (39.1%, 38.5%), diarrhea (26.0%, 24.5%) and nausea
(26.5%, 23.4%). Common adverse events that were reported more frequently
in the letermovir arm than the placebo arm included: vomiting (18.5%,
13.5%), cough (14.2%, 10.4%) and peripheral edema (14.5%, 9.4%). The
most common serious adverse events reported for the letermovir and
placebo arms, respectively, were: infection (20.6%, 18.8%), GVHD (9.9%,
10.4%) and acute kidney injury (1.3%, 4.7%). Letermovir was not
associated with myelotoxicity or nephrotoxicity.

About letermovir

Letermovir is an investigational once-daily antiviral medicine under
development for the prevention of CMV infection and disease. It is a
member of a new class of non-nucleoside CMV inhibitors (3,4
dihydro-quinazolines) and inhibits viral replication by specifically
targeting the viral terminase complex. Letermovir has no activity
against other viruses. Letermovir has been granted orphan designation by
the European Medicines Agency, the U.S. Food and Drug Administration
(FDA) and the Japanese Ministry of Health, Labour and Welfare for the
prevention of CMV infection and disease in at-risk populations.
Letermovir also has been granted Fast Track designation by the FDA.

Under an agreement signed in 2012, Merck (through a subsidiary)
purchased worldwide rights to develop and commercialize letermovir from
AiCuris GmbH & Co KG (www.aicuris.com).

About CMV infection

CMV is a common virus that infects people of all ages. Many adults in
the United States are CMV seropositive, meaning they have CMV antibodies
in their blood, indicating a previous exposure or primary infection to
CMV. People with normal immune systems rarely develop CMV symptoms after
initial infection, with the virus typically remaining inactive or latent
in the body for life. A weakened immune system may give the virus a
chance to reactivate, potentially leading to symptomatic disease or a
secondary infection due to other pathogens. CMV disease can lead to
end-organ damage, including gastrointestinal tract disease, pneumonia or
retinitis. Transplant recipients who develop CMV infection
post-transplant are at increased risk for injury to a transplanted
organ. In severely immunocompromised patients, CMV infection can be
life-threatening.

About Merck

For over a century, 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
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Forward-Looking Statement

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).

Merck
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Robert Consalvo, 908-236-1127
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