VERQUVO Approved for Reduction of Risk of
Cardiovascular Death and Heart Failure (HF) Hospitalization
Following a Hospitalization for HF or Need for Outpatient
Intravenous (IV) Diuretics in Adults with Symptomatic Chronic Heart
Failure and Ejection Fraction Less than 45%
VERQUVO is the First Soluble Guanylate
Cyclase Stimulator, Approved to Treat Heart Failure
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced that the U.S. Food and Drug Administration
(FDA) has approved VERQUVO, a soluble guanylate cyclase (sGC)
stimulator, to reduce the risk of cardiovascular death and heart
failure hospitalization following a hospitalization for heart
failure or need for outpatient intravenous (IV) diuretics in adults
with symptomatic chronic heart failure and ejection fraction less
than 45%. The approval of VERQUVO by the FDA, which is the first
treatment for chronic heart failure approved specifically for
patients following a hospitalization for heart failure or need for
outpatient IV diuretics, is based on the results of the pivotal
Phase 3 VICTORIA trial and follows a priority regulatory review.
VERQUVO (vericiguat) 2.5 mg, 5 mg, and 10 mg tablets is being
jointly developed with Bayer AG.
The VERQUVO label contains a boxed warning that indicates that
VERQUVO should not be administered to pregnant females because it
may cause fetal harm. For more information, see “Selected Safety
Information” below.
“Patients with symptomatic chronic heart failure and reduced
ejection fraction have a high risk for hospitalization after
experiencing symptoms of heart failure requiring outpatient IV
diuretic treatment or hospitalization. By some estimates, more than
half of these patients are rehospitalized within a month of
discharge due to a worsening event and approximately one in five
die within two years,” said Dr. Paul W. Armstrong, cardiologist and
Distinguished University Professor of Medicine at the Canadian
VIGOUR Centre, University of Alberta, and study chair of the
VICTORIA trial. “The approval of VERQUVO provides doctors, health
care professionals, and patients with a welcome new option to
current available therapies.”
In VICTORIA, the primary efficacy objective was to determine
whether VERQUVO is superior to placebo, both in combination with
other heart failure therapies, in reducing the risk of
cardiovascular death or heart failure hospitalization in adults
with symptomatic chronic heart failure and ejection fraction less
than 45% following a worsening heart failure event. VERQUVO met the
primary efficacy objective based on a time-to-event analysis
(hazard ratio [HR]: 0.90, 95% confidence interval [CI], 0.82-0.98;
p=0.019). Over the course of the study, there was a 4.2% reduction
in annualized absolute risk with VERQUVO compared with placebo.
Therefore, 24 patients would need to be treated over an average of
one year to prevent one primary endpoint event.
“VERQUVO has been shown to reduce the risk of cardiovascular
death and heart failure hospitalization following a hospitalization
for heart failure or need for outpatient IV diuretics. We are
pleased to offer a meaningful new treatment option for appropriate
patients with symptomatic chronic heart failure,” said Dr. Roy
Baynes, senior vice president and head of global clinical
development, chief medical officer, Merck Research Laboratories.
“This approval builds upon Merck’s proud history of developing
therapies for the treatment of patients with cardiovascular
disease.”
Data Supporting the Approval The approval of VERQUVO was
based on data from VICTORIA (NCT02861534), a randomized,
parallel-group, placebo-controlled, double-blind, event-driven,
multi-center clinical trial comparing VERQUVO to placebo in 5,050
adult patients with symptomatic chronic heart failure (New York
Heart Association [NYHA] class II-IV) and left ventricular ejection
fraction (LVEF) less than 45%, following a worsening heart failure
event. A worsening heart failure event was defined as heart failure
hospitalization within six months or less prior to randomization or
use of outpatient IV diuretics for heart failure within three
months or less prior to randomization. In VICTORIA, the primary
endpoint was a composite of time to first event of cardiovascular
death or hospitalization for heart failure. The median follow-up
for the primary endpoint was 11 months. VERQUVO was superior to
placebo in reducing the risk of cardiovascular death or heart
failure hospitalization based on a time-to-event analysis.
Patients received up to the target maintenance dose of VERQUVO
10 mg once daily or matching placebo. Therapy was initiated at
VERQUVO 2.5 mg once daily and increased in approximately two-week
intervals to 5 mg once daily and then 10 mg once daily, as
tolerated. Placebo doses were similarly adjusted. After
approximately one year, 90% of patients in both the VERQUVO and
placebo arms were treated with the 10 mg target maintenance
dose.
Study participants were: 76% male, 64% Caucasian, 22% Asian, and
5% Black. The mean age was 67 years. At randomization, 59% of
patients were NYHA Class II, 40% were NYHA Class III and 1% were
NYHA Class IV. The mean LVEF was 29%. Approximately half of all
patients had an EF less than 30%, and 14% of patients had an EF
between 40% and 45%. Sixty-seven percent of the patients in
VICTORIA were enrolled within three months of a heart failure
hospitalization index event; 17% were enrolled within three to six
months of heart failure hospitalization, and 16% were enrolled
within three months of outpatient treatment with IV diuretics for
worsening heart failure. The median NT-pro B-type natriuretic
peptide (NT-proBNP) level was 2800 pg/mL at randomization.
Study participants were on standard of care. At baseline, 93% of
patients were receiving a beta-blocker, 73% were receiving an
angiotensin-converting enzyme (ACE) inhibitor or angiotensin II
receptor blocker (ARB), 70% were receiving a mineralocorticoid
receptor antagonist (MRA), 15% were receiving a combination of an
angiotensin receptor and neprilysin inhibitor (ARNI), 28% had an
implantable cardiac defibrillator and 15% had a biventricular
pacemaker. Ninety-one percent of patients were treated with two or
more heart failure medications (beta blocker, any renin-angiotensin
system [RAS] inhibitor or MRA) and 60% of patients were treated
with all three. At baseline, 6% of patients were receiving
ivabradine and 3% a sodium glucose co-transporter 2 (SGLT2)
inhibitor.
In the VICTORIA trial, VERQUVO demonstrated an adverse event
profile similar to placebo. The adverse drug reactions occurring
more commonly with VERQUVO than placebo and in greater than or
equal to 5% of patients treated with VERQUVO in VICTORIA were
hypotension (16% vs 15%) and anemia (10% vs 7%). The VICTORIA trial
included a total of 2,519 patients treated with VERQUVO (up to 10
mg once daily). The mean duration of VERQUVO exposure was one year,
and the maximum duration was 2.6 years.
About VERQUVO® (vericiguat) tablets for once daily oral use
(2.5 mg, 5 mg and 10 mg) Vericiguat is a stimulator of soluble
guanylate cyclase (sGC), an important enzyme in the nitric oxide
(NO) signaling pathway. When NO binds to sGC, the enzyme catalyzes
the synthesis of intracellular cyclic guanosine monophosphate
(cGMP), a second messenger that plays a role in the regulation of
vascular tone, cardiac contractility, and cardiac remodeling. Heart
failure is associated with impaired synthesis of NO and decreased
activity of sGC, which may contribute to myocardial and vascular
dysfunction. By directly stimulating sGC, independently of and
synergistically with NO, vericiguat augments levels of
intracellular cGMP, leading to smooth muscle relaxation and
vasodilation.
Selected Safety Information for VERQUVO WARNING:
EMBRYO-FETAL TOXICITY Females of reproductive potential: Exclude
pregnancy before the start of treatment. To prevent pregnancy,
females of reproductive potential must use effective forms of
contraception during treatment and for one month after stopping
treatment. Do not administer VERQUVO to a pregnant female because
it may cause fetal harm.
VERQUVO is contraindicated in patients with concomitant use of
other soluble guanylate cyclase (sGC) stimulators. VERQUVO is
contraindicated in pregnancy. Based on data from animal
reproduction studies, VERQUVO may cause fetal harm when
administered to a pregnant woman. Advise females of reproductive
potential of the potential risk to a fetus. Obtain a pregnancy test
before the start of treatment. Advise females of reproductive
potential to use effective contraception during treatment with
VERQUVO and for at least one month after the final dose.
In a clinical trial, the most commonly observed adverse events
with VERQUVO vs placebo, occurring at a frequency greater than or
equal to 5%, were hypotension (16% vs 15%) and anemia (10% vs
7%).
There are no data on the presence of VERQUVO in human milk, the
effects on the breastfed infant, or effects on milk production.
Because of the potential for serious adverse reactions in breastfed
infants from VERQUVO, advise women not to breastfeed during
treatment with VERQUVO.
Concomitant use of VERQUVO with PDE-5 inhibitors is not
recommended because of the potential for hypotension.
About the Worldwide Collaboration Between Bayer and Merck
Since October 2014, Bayer and Merck (known as MSD outside of the
United States and Canada) have pursued a worldwide collaboration in
the field of sGC modulators. The collaboration brings together two
leading companies that have stated their intent to fully evaluate
this therapeutic class in areas of unmet medical need. The
vericiguat program is being co-developed by Bayer and Merck. Merck
has the commercial rights to vericiguat in the U.S. and Bayer has
the exclusive commercial rights in the rest of world. The companies
share equally the costs of the development of vericiguat.
About Heart Failure with Reduced Ejection Fraction Heart
failure with reduced ejection fraction (HFrEF), formerly known as
systolic heart failure, is characterized by the compromised ability
of the heart to pump blood sufficiently during its contraction
phase. In the U.S., approximately 6.2 million adults (20 years of
age and older) have heart failure, and approximately 50% of heart
failure patients have HFrEF. An observational, cohort analysis of
PINNACLE registry data showed that approximately half of patients
with worsening chronic HFrEF are rehospitalized within 30 days of a
worsening event, and an estimated one in five patients with
worsening chronic HFrEF will die within two years.
About Merck For more than 125 years, Merck, 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 in pursuit of our mission to save
and improve lives. We demonstrate our commitment to patients and
population health by increasing access to health care through
far-reaching policies, programs and partnerships. Today, Merck
continues to be at the forefront of research to prevent and treat
diseases that threaten people and animals – including cancer,
infectious diseases such as HIV and Ebola, and emerging animal
diseases – as we aspire to be the premier research-intensive
biopharmaceutical company in the world. For more information, visit
www.merck.com and connect with us on Twitter, Facebook, Instagram,
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 the global outbreak of novel coronavirus disease
(COVID-19); 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 2019
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, including Boxed Warning,
for VERQUVO (vericiguat) at
https://www.merck.com/product/usa/pi_circulars/v/verquvo/verquvo_pi.pdf
and Medication Guide at
https://www.merck.com/product/usa/pi_circulars/v/verquvo/verquvo_mg.pdf.
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