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February 24, 2017 4:00 pm ET

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the first Phase 3 study results for V212, the company’s
investigational inactivated varicella zoster virus vaccine (VZV) for the
prevention of herpes zoster or HZ, also known as shingles, in
immunocompromised patients. This was a double-blind, randomized,
placebo-controlled, multi-center trial to study safety, tolerability,
efficacy and immunogenicity of inactivated VZV Vaccine in Recipients of
Autologous Hematopoietic Stem Cell Transplants (auto-HSCT). In the
trial, V212 met its primary endpoint and reduced the incidence of
confirmed HZ cases by an estimated 64 percent (95% CI, 0.48, 0.75) in
recipients of auto-HSCT. These results were presented today, as an oral
presentation, at the combined annual meetings of the Center for
International Blood & Marrow Transplant Research (CIBMTR) and the
American Society for Blood and Marrow Transplantation (ASBMT) during a
“Best Abstracts” session in Orlando, Florida.

Secondary endpoint findings from the study showed that V212 reduced the
incidence of moderate-to-severe HZ pain by an estimated 69.5 percent,
utilizing the Zoster Brief Pain Inventory (ZBPI) score. V212
demonstrated an estimated 83.7 percent reduction of the incidence of
post-herpetic neuralgia (PHN) beyond 90 days after onset of HZ. In the
study PHN was defined as pain in the area of the HZ rash with a “worst
pain in the last 24 hours” score of 3 or greater (on a 0 to 10 scale) on
the ZBPI that persists or appears 90 days or beyond after HZ rash onset
following auto-HSCT.

In addition, V212 showed reduction of other HZ complications by an
estimated 73.5 percent. These other complications included
hospitalization or prolongation of hospitalization due to HZ;
disseminated HZ (including disseminated HZ rash or VZV viremia);
visceral HZ, ophthalmic HZ; neurological impairment due to HZ; or
administration of intravenous acyclovir therapy for treatment of HZ post
auto-HSCT.

Because subjects receiving auto-HSCT are immunocompromised, they are at
six-times greater risk of developing shingles than the general
population. In 2014, an estimated 11,000 people underwent stem cell
transplantation in the United States. ZOSTAVAX ^® (zoster
vaccine live), the only approved vaccine indicated for the prevention of
shingles in individuals 50 years of age or older, is contraindicated in
immunocompromised patients. ZOSTAVAX is not indicated for the treatment
of zoster or postherpetic neuralgia. ZOSTAVAX should not be used for
prevention of primary varicella infection (Chickenpox).

“Patients undergoing auto-HSCT have an increased risk of HZ and
associated complications due to impaired cellular immunity. These
results indicate that V212 might offer a way to help reduce the risk of
HZ and HZ-related complications in this vulnerable, immunocompromised
patient population,” said Eliav Barr, M.D., senior vice president, Merck
Research Laboratories. “We look forward to exploring these data further
and to reviewing the results of an additional Phase 3 study that is
underway in immunocompromised patients with malignancies.”

About the Study (NCT01229267)

The Phase 3 randomized, double-blind, placebo-controlled, multi-center
trial included patients 18 years or older, undergoing auto-HSCT for
malignancy or any other indication, with a history of varicella
infection and/or seropositive for VZV antibody. Subjects had no
malignancy with more than two disease relapses (except Hodgkin
lymphoma), no planned tandem transplants, no previous VZV vaccination,
no HZ infection within the previous year, and no intended antiviral
prophylaxis for >6 months after auto-HSCT (antiviral prophylaxis for <6
months was allowed).

Eligible subjects (n=1,230) were randomly assigned to receive a 4-dose
regimen of V212 from a consistency lot (a lot having a targeted potency
as required by regulators in order to demonstrate that the vaccine can
be manufactured consistently), a high-antigen lot (a lot having a higher
antigen potency added to assess further the safety profile of V212), or
placebo. Randomization was stratified by age (younger than 50 years vs.
older than 50 years) and by intended duration of post-transplant
antiviral prophylaxis (≤3 months vs. >3 to 6 months).

Dose 1 of V212 or placebo was given within approximately 30 days before
auto-HSCT, and doses 2, 3, and 4 were given approximately 30, 60, and 90
days after auto-HSCT. Subjects were followed for the duration of the
study for efficacy with cases of HZ confirmed by PCR and/or adjudicated
by a blinded data monitoring committee. The average follow-up time for
HZ surveillance was approximately 2.3 years (median: 2.6 years) post
vaccination.

The most common systemic adverse events observed in both the vaccine and
placebo arms of the study at a incidence rate of 15 percent or more in
either group, included diarrhea, nausea, pyrexia, mucosal inflammation,
thrombocytopenia, febrile neutropenia, vomiting, anemia, neutropenia,
decreased appetite, fatigue, hypokalemia, and constipation.

Serious adverse events occurred in 216 (32.9%) subjects receiving the
consistency lot or high-antigen lot and in 181 (32.7%) subjects
receiving placebo for up to 28 days after the fourth vaccination dose.
The most frequent serious adverse event observed was febrile neutropenia
observed in 5.3 percent of the vaccine group and 4.9 percent in the
placebo group. Serious vaccine-related adverse events occurred in 5
(0.8%) subjects receiving consistency lot or high-antigen lot and in 5
(0.9%) subjects receiving placebo.

About V212

V212 is Merck’s investigational inactivated VZV vaccine for the
prevention of HZ and HZ-related complications in immunocompromised
subjects age 18 years and above. The Phase 3 trial in auto-HSCT
recipients has been completed. Another Phase 3 trial in subjects with
malignancies is ongoing.

About ZOSTAVAX

^®
(zoster vaccine live)

ZOSTAVAX is a live attenuated virus vaccine indicated for prevention of
herpes zoster (shingles) in individuals 50 years of age and older.
ZOSTAVAX is not indicated for the treatment of zoster or postherpetic
neuralgia. ZOSTAVAX should not be used for prevention of primary
varicella infection (Chickenpox).

Select Safety Information

Vaccination with ZOSTAVAX does not result in protection of all vaccine
recipients.

ZOSTAVAX is contraindicated in: persons with a history of anaphylactic
or anaphylactoid reaction to gelatin, neomycin, or any other component
of the vaccine; persons with a history of primary or acquired
immunodeficiencies; persons on immunosuppressive therapy; pregnant women
or women of childbearing age.

A reduced immune response to ZOSTAVAX was observed in individuals who
received concurrent administration of PNEUMOVAX^®23
(Pneumococcal Vaccine Polyvalent) and ZOSTAVAX compared with individuals
who received these vaccines 4 weeks apart. Consider administration of
the two vaccines separated by at least 4 weeks.

Serious vaccine-related adverse reactions that have occurred following
vaccination with ZOSTAVAX include asthma exacerbation and polymyalgia
rheumatica. Other serious adverse events reported following vaccination
with ZOSTAVAX (zoster vaccine live) include cardiovascular events
(congestive heart failure, pulmonary edema). Common adverse reactions
occurring in ≥1% of vaccinated individuals during clinical trials
include injection-site reactions (erythema, pain/tenderness, swelling,
hematoma, pruritus, warmth) and headache.

Transmission of vaccine virus may occur between vaccinees and
susceptible contacts.

Deferral should be considered in acute illness (for example, in the
presence of fever) or in subjects with active untreated tuberculosis.

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,
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YouTube
and LinkedIn.

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).

Please see Prescribing Information for ZOSTAVAX at

https://www.merck.com/product/usa/pi_circulars/z/zostavax/zostavax_pi2.pdf


and Patient Information for ZOSTAVAX at

http://www.merck.com/product/usa/pi_circulars/z/zostavax/zostavax_ppi.pdf

.

Merck
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