KIRKLAND, QC, Dec. 14, 2017 /CNW Telbec/ - Merck &
Co., Inc. (NYSE: MRK), known as MSD outside Canada and the
United States, announced today that the recently approved
PREVYMIS™ (letermovir) is expected to be available in Canada by the end of December 2017. The product is indicated for the
prophylaxis of cytomegalovirus (CMV) infection in adult
CMV-seropositive recipients [R+] of an allogeneic hematopoietic
stem cell transplant (HSCT).
CMV is a common and potentially serious viral infection in
allogeneic HSCT recipients. CMV-seropositive patients who undergo
an HSCT are at high risk for CMV reactivation. Any level of CMV
infection is associated with increased mortality in HSCT
patients.
In the pivotal Phase 3 clinical trial supporting approval,
significantly fewer patients in the letermovir group (38%,
n=122/325) compared to the placebo group (61%, n=103/170) developed
clinically significant CMV infection, discontinued treatment or had
missing data through Week 24 post-HSCT [treatment difference: -23.5
(95% confidence interval -32.5 to -14.6), (p<0.0001)], the
primary efficacy endpoint. Patients in both arms with clinically
significant CMV infection were discontinued from trial and began
anti-CMV therapy according to local practice. All-cause mortality
in patients receiving letermovir was lower compared to placebo, 12%
vs. 17%, respectively, at Week 24 post-transplant. In this study,
the incidence of bone marrow suppression in the letermovir group
was comparable to the placebo group. The median time to engraftment
was 19 days in the letermovir group and 18 days in the placebo
group.
Clinical Data Supporting Letermovir
To evaluate
prophylaxis with letermovir as a preventive strategy for CMV
infection in transplant recipients at high risk for CMV
reactivation, the efficacy of letermovir was assessed in a
multicenter, double-blind, placebo-controlled Phase 3 trial in
adult CMV-seropositive recipients [R+] of an allogeneic HSCT.
Patients were randomized (2:1) to receive either letermovir at a
dose of 480 mg once daily adjusted to 240 mg when co-administered
with cyclosporine, or placebo. Study drug was initiated after HSCT
(at any time from Day 0-28 post-transplant) and continued through
Week 14 post-transplant. Patients were monitored through Week 24
post-transplant for the primary efficacy endpoint, with continued
follow-up through Week 48 post-transplant. The primary efficacy
endpoint was the incidence of clinically significant CMV infection
through Week 24 post-transplant, defined as the occurrence of
either CMV end-organ disease, or initiation of anti-CMV pre-emptive
therapy based on documented CMV viremia and the clinical condition
of the patient. The Non-Completer equals Failure approach was used,
where patients who discontinued from the trial prior to Week 24
post-transplant or had a missing outcome at Week 24 post-transplant
were counted as failures.
Among the 565 treated patients, 34% were engrafted at baseline
and 30% had one or more factors associated with additional risk for
CMV reactivation. The most common primary reasons for transplant
were acute myeloid leukemia (38%), myelodysplastic syndrome (15%),
and lymphoma (13%). Fewer patients in the letermovir group had
clinically significant CMV infection by Week 24 post-HSCT compared
to the placebo group, 18% vs. 42%, respectively. At Week 14
post-transplant, the Kaplan-Meier (K-M) event rate for clinically
significant CMV infection was 6.8% in the letermovir group compared
to 41.3% in the placebo group. Letermovir demonstrated significant
benefit compared to placebo in time to clinically significant CMV
infection through Week 24 post-HSCT (18.9% vs. 44.3% cumulative
rate; stratified log-rank test, two-sided p-value <0.0001).
Efficacy consistently favoured letermovir across subgroups
including low and high risk for CMV reactivation, stem cell source,
donor mismatch, haploidentical transplant, conditioning regimens,
and concomitant immunosuppressive regimens.
Post-hoc analysis demonstrated that among PREVYMIS-treated
patients, inclusion in the high-risk stratum for CMV reactivation
at baseline, occurrence of graft-versus-host disease (GVHD), and
steroid use at any time after randomization may be associated with
the development of clinically significant CMV infection between
Week 14 and Week 24 post-transplant.
The Kaplan-Meier event rate for all-cause mortality in the
PREVYMIS vs. placebo groups was 12% vs. 17% at Week 24
post-transplant, and 24% vs. 28% at Week 48 post-transplant. The
most commonly reported adverse reactions occurring in at least 1%
of subjects in the letermovir group through Week 24 post-transplant
and at a frequency greater than placebo were: nausea, diarrhea, and
vomiting.
About PREVYMIS (letermovir)
PREVYMIS 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. Cross
resistance is not likely with drugs outside of this class. 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). For more information,
please consult the Canadian PREVYMIS (letermovir) product monograph
here.
About CMV and Treatment
CMV is a common virus that
infects people of all ages. Many adults in Canada are CMV seropositive, meaning they have
CMV antibodies in their blood, indicating a previous exposure to or
primary infection with 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 transplant failure and death. CMV prophylaxis
with certain existing antivirals has been associated with
drug-specific effects, including myelosuppression and renal
toxicity, in HSCT recipients.
About Merck
For over 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 about our operations in Canada, visit www.merck.ca and connect with us
on YouTube and Twitter @MerckCanada.
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 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).
*Please consult the Canadian PREVYMIS (letermovir) product
monograph here.
SOURCE Merck Canada Inc.