Japan’s Ministry of Health, Labor and
Welfare Approves Molnupiravir for the Treatment of SARS-CoV-2
Infection
Molnupiravir, First Oral COVID-19 Antiviral
Medicine To Receive Authorization in the World, Now Authorized in
U.S., U.K. and Japan; Regulatory Submissions Are Under Review
Around the World
Merck (NYSE: MRK), known as MSD outside the United States and
Canada, and Ridgeback Biotherapeutics today announced that Japan’s
Ministry of Health, Labor and Welfare has granted Special Approval
for Emergency in Japan for molnupiravir, an investigational oral
antiviral medicine, for infectious disease caused by SARS-CoV-2.
Special Approval for Emergency is the process under Article 14-3 of
the Pharmaceuticals and Medical Devices Act to approve a medical
product swiftly in an emergency situation to protect public health.
Under a previously announced supply agreement, the Japanese
government will purchase 1.6 million courses of molnupiravir to
accelerate access to patients.
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“As a single oral medicine that can be taken at home, early
treatment with molnupiravir significantly reduced the risk of
hospitalization or death in patients at high risk for progressing
to severe COVID-19. Importantly for patients, there were markedly
fewer deaths among those taking molnupiravir in our clinical study.
We believe that molnupiravir will be a critical addition to the
measures available to help curb the impact of COVID-19 on patients,
healthcare systems and public health in Japan,” said Dr. Dean Y.
Li, president, Merck Research Laboratories. “All of us at Merck
have embraced our responsibility to bring this important medicine
forward to patients globally as quickly as possible.”
“We are proud to reach this important milestone alongside our
collaborators, patients and physicians,” said Wendy Holman, chief
executive officer, Ridgeback Biotherapeutics. “We are confident in
the promise of molnupiravir as a medicine that can be taken at home
with no known drug-drug interactions and believe it will have a
positive impact as part of the global effort to fight the COVID-19
pandemic.”
Molnupiravir was the first oral COVID-19 antiviral medicine to
receive authorization on Nov. 4, when the U.K.’s Medicines and
Healthcare Products Regulatory Agency granted authorization. In the
E.U., the European Medicines Agency issued a positive scientific
opinion for molnupiravir under Article 5.3 regulation 726/2004,
which is intended to support national decision-making on the
possible use of molnupiravir prior to marketing authorization. On
Dec. 23, the U.S. Food and Drug Administration granted Emergency
Use Authorization for molnupiravir. Regulatory applications are
under review or are in the process of being submitted for
molnupiravir around the world.
In Japan, LAGEVRIO® (molnupiravir) is the planned trademark for
molnupiravir. Molnupiravir is available in certain markets outside
the U.S. as LAGEVRIO.
About the MOVe-OUT Study
The approval is based on positive results from a planned interim
analysis from the Phase 3 MOVe-OUT clinical trial (NCT04575597),
which evaluated molnupiravir 800 mg twice-daily in
non-hospitalized, unvaccinated adult patients with
laboratory-confirmed mild-to-moderate COVID-19, symptom onset
within five days of study randomization, and at least one risk
factor associated with poor disease outcomes (e.g. heart disease,
diabetes). The primary efficacy objective of MOVe-OUT is to
evaluate the efficacy of molnupiravir 800 mg twice daily for five
days compared to placebo as assessed by the percentage of
participants who are hospitalized and/or die through Day 29.
At the interim analysis, which was the primary analysis
timepoint of the study, molnupiravir significantly reduced the risk
of hospitalization and death: 14.1% (53/377) of patients in the
placebo group were hospitalized or died, compared to 7.3% (28/385)
of patients who received molnupiravir who were hospitalized; at the
interim analysis, no patients who took molnupiravir died through
Day 29, compared to eight patients who received placebo. The
absolute risk reduction was 6.8 percentage points (95% CI: 2.4,
11.3; p=0.0012, one-sided), which is approximately a 50% relative
reduction in the risk of hospitalization or death through Day 29
for molnupiravir compared with placebo. In the all randomized
analysis (n=1433), molnupiravir had a lower risk of hospitalization
or death through Day 29: 9.7% (68/699) of patients in the placebo
group compared to 6.8% (48/709) of patients in the molnupiravir
group, for an absolute risk reduction of 3.0% (95% CI: 0.1, 5.9)
and a relative risk reduction of 30%. Nine deaths were reported in
the placebo group (29-day all-cause mortality rate of 1.3%) and one
in the molnupiravir group (29-day all-cause mortality rate of
0.1%), representing a relative reduction in the risk of death of
89% (95% CI: 14, 99).
Adverse reactions were observed in 12.4% (48/386 participants)
in the molnupiravir 800 mg group. The most common observed adverse
reactions (greater than or equal to 1%) were diarrhea 3.1% (12/386
participants), nausea 2.3% (9/386 participants), dizziness 1.3%
(5/386 participants) and headache 1.0% (4/386 participants).
About Merck’s Global Efforts to Accelerate Access to
Molnupiravir Following Regulatory Authorizations or
Approvals
Global access has been a priority for Merck and Ridgeback since
the inception of their molnupiravir collaboration. The companies
are committed to providing timely access to molnupiravir globally
through our comprehensive supply and access approach, which
includes investing at risk to produce millions of courses of
therapy; tiered pricing based on the ability of governments to
finance health care; entering into supply agreements with
governments; and granting voluntary licenses to generic
manufacturers and to the Medicines Patent Pool to make generic
molnupiravir available in more than 100 low- and middle-income
countries following local regulatory authorizations or
approvals.
Supply: In anticipation of the results from MOVe-OUT and
the potential for regulatory authorization or approval, Merck has
been producing molnupiravir at risk and will produce 10 million
courses of treatment by the end of 2021, with at least 20 million
courses to be produced in 2022. To date, Merck has shipped
molnupiravir to 14 countries; in countries where it is approved or
authorized, patients have begun to receive the drug.
Supply agreements: Merck entered into a procurement
agreement with the U.S. Government under which the company will
supply approximately 3.1 million courses of molnupiravir to the
U.S. Government, upon Emergency Use Authorization or approval from
the U.S. Food and Drug Administration. Merck has entered into
advance purchase and supply agreements for molnupiravir with
governments for over 30 countries worldwide, including Australia,
Canada, Korea, Japan, Thailand, United Kingdom and United States,
pending regulatory authorizations, and is currently in discussions
with additional governments. Merck plans to implement a tiered
pricing approach based on World Bank country income criteria to
reflect countries’ relative ability to finance their health
response to the pandemic.
Voluntary licenses: As part of its commitment to
widespread global access, Merck previously announced that it has
entered into a licensing agreement with the Medicines Patent Pool
to increase broad access for molnupiravir in low- and middle-income
countries. Additionally, Merck previously announced that the
company has entered into non-exclusive voluntary licensing
agreements for molnupiravir with established generic manufacturers
to accelerate availability of molnupiravir in more than 100 low-
and middle-income countries following approvals or emergency
authorization by local regulatory agencies.
Merck continues to discuss additional measures and
collaborations to accelerate broad, global access to
molnupiravir.
Authorized Use of Molnupiravir in the U.S.
The U.S. Food and Drug Administration (FDA) has issued an EUA
for the emergency use of the unapproved molnupiravir, a nucleoside
analogue that inhibits SARS-CoV-2 replication by viral mutagenesis,
for the treatment of mild to moderate coronavirus disease 2019
(COVID-19) in adults with positive results of direct SARS-CoV-2
viral testing, and who are at high risk for progression to severe
COVID-19, including hospitalization or death, and for whom
alternative COVID-19 treatment options authorized by FDA are not
accessible or clinically appropriate. Molnupiravir is not
FDA-approved for any use including for use for the treatment of
COVID-19. Prior to initiating treatment with molnupiravir,
carefully consider the known and potential risks and benefits.
Molnupiravir is authorized only for the duration of the
declaration that circumstances exist justifying the authorization
of the emergency use of molnupiravir under section 564(b)(1) of the
Federal, Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1),
unless the authorization is terminated or revoked sooner.
Molnupiravir is not authorized for use in patients less than 18
years of age or who are hospitalized due to COVID-19. Benefit of
treatment with molnupiravir has not been observed in subjects when
treatment was initiated after hospitalization due to COVID-19.
Molnupiravir is not authorized for use for longer than five
consecutive days. Molnupiravir is not authorized for pre-exposure
or post-exposure prophylaxis for prevention of COVID-19.
Molnupiravir may only be prescribed for an individual patient by
physicians, advanced practice registered nurses, and physician
assistants that are licensed or authorized under state law to
prescribe drugs in the therapeutic class to which molnupiravir
belongs (i.e., anti-infectives).
Selected Safety Information for Molnupiravir
Contraindications
No contraindications have been identified based on the limited
available data on the emergency use of molnupiravir authorized
under this EUA.
Warnings and Precautions
There are limited clinical data available for molnupiravir.
Serious and unexpected adverse events may occur that have not been
previously reported with molnupiravir use.
Molnupiravir is not recommended for use during pregnancy. Based
on findings from animal reproduction studies, molnupiravir may
cause fetal harm when administered to pregnant individuals. There
are no available human data on the use of molnupiravir in pregnant
individuals to evaluate the risk of major birth defects,
miscarriage or adverse maternal or fetal outcomes.
Molnupiravir is authorized to be prescribed to a pregnant
individual only after the healthcare provider has determined that
the benefits would outweigh the risks for that individual patient.
If the decision is made to use molnupiravir during pregnancy, the
prescribing healthcare provider must document that the known and
potential benefits and the potential risks of using molnupiravir
during pregnancy were communicated to the pregnant individual.
There is a pregnancy surveillance program that monitors
pregnancy outcomes in individuals exposed to molnupiravir during
pregnancy. The prescribing healthcare provider must document that a
pregnant individual was made aware of Merck’s pregnancy
surveillance program at 1-877-888-4231 or
pregnancyreporting.msd.com. If the pregnant individual agrees to
participate in the pregnancy surveillance program and allows the
prescribing healthcare provider to disclose patient specific
information to Merck, the prescribing healthcare provider must
provide the patient’s name and contact information to Merck.
Pregnant individuals exposed to molnupiravir can also report the
exposure by contacting Merck at 1-877-888-4231 or
pregnancyreporting.msd.com.
Advise individuals of childbearing potential of the potential
risk to a fetus and to use an effective method of contraception
correctly and consistently during treatment with molnupiravir and
for 4 days after the final dose.
Prior to initiating treatment with molnupiravir, assess whether
an individual of childbearing potential is pregnant or not, if
clinically indicated.
Molnupiravir is not authorized for use in patients less than 18
years of age because it may affect bone and cartilage growth. The
safety and efficacy of molnupiravir have not been established in
pediatric patients.
Adverse Reactions
The most common adverse reactions occurring in ≥1% of subjects
in the molnupiravir treatment group in the Phase 3 double-blind
MOVe-OUT study were diarrhea (2% versus placebo at 2%), nausea (1%
versus placebo at 1%), and dizziness (1% versus placebo at 1%) all
of which were Grade 1 (mild) or Grade 2 (moderate).
Serious adverse events occurred in 7% of subjects receiving
molnupiravir and 10% receiving placebo; most serious adverse events
were COVID-19 related. Adverse events leading to death occurred in
2 (<1%) of the subjects receiving molnupiravir and 12 (2%) of
subjects receiving placebo.
Drug Interactions
No drug interactions have been identified based on the limited
available data on the emergency use of molnupiravir. No clinical
drug-drug interaction trials of molnupiravir with concomitant
medications, including other treatments for mild to moderate
COVID-19, have been conducted.
Pregnancy/Breastfeeding
There are no data on the presence of molnupiravir or its
metabolites in human milk. It is unknown whether molnupiravir has
an effect on the breastfed infant or effects on milk production.
Based on the potential for adverse reactions in the infant from
molnupiravir, breastfeeding is not recommended during treatment
with molnupiravir and for 4 days after the final dose. A lactating
individual may consider interrupting breastfeeding and may consider
pumping and discarding breast milk during treatment and for 4 days
after the last dose of molnupiravir.
Males of Reproductive Potential
Nonclinical studies to fully assess the potential for
molnupiravir to affect offspring of treated males have not been
completed. Advise sexually active individuals with partners of
childbearing potential to use a reliable method of contraception
correctly and consistently during treatment and for at least 3
months after last dose of molnupiravir. The risk beyond three
months after the last dose of molnupiravir is unknown.
Required Reporting for Serious Adverse Events and Medication
Errors
The prescribing healthcare provider and/or the provider’s
designee are/is responsible for mandatory reporting of all serious
adverse events and medication errors potentially related to
molnupiravir within 7 calendar days from the healthcare provider’s
awareness of the event.
Submit adverse event and medication error reports, using FDA
Form 3500, to FDA MedWatch using one of the following methods:
- Complete and submit the report online:
www.fda.gov/medwatch/report.htm
- Complete and submit a postage-paid FDA Form 3500
(https://www.fda.gov/media/76299/download) and return by:
- Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787,
or
- Fax to 1-800-FDA-0178
- Call 1-800-FDA-1088 to request a reporting form
In addition, please provide a copy of all FDA MedWatch forms
to:
Merck Sharp & Dohme Corp., a subsidiary
of Merck & Co., Inc., Kenilworth, NJ USA by: Fax: 215-616-5677
E-mail: dpoc.usa@merck.com
About Molnupiravir
Molnupiravir (MK-4482 and EIDD-2801) is an investigational,
orally administered nucleoside analogue that inhibits replication
of SARS-CoV-2, the causative agent of COVID-19. Merck and
Ridgeback’s “orange COVID-19 pill” is a Swedish Orange opaque
capsule with the Merck corporate logo and “82” printed in white
ink, available in certain markets outside of the U.S. as
LAGEVRIO®.
Results from the Phase 3 MOVe-OUT study demonstrated the
efficacy benefit of molnupiravir treatment was generally consistent
across patients infected with SARS-CoV-2 variants of concern,
Delta, Gamma and Mu. Preliminary preclinical data has shown that
molnupiravir has antiviral activity against the newly identified
variant, Omicron (B1.1.529). Molnupiravir has yet to be evaluated
against Omicron in clinical studies.
Molnupiravir was invented at Emory University. Drug Innovation
Ventures at Emory (DRIVE), LLC, which was formed by Emory to
develop early-stage drug candidates for viral diseases of global
concern, advanced molnupiravir through IND submission. Emory/DRIVE
received some research funding from the U.S. Department of Defense
and the U.S. National Institutes of Health. Molnupiravir is being
developed by Merck in collaboration with Ridgeback Biotherapeutics.
Ridgeback received an upfront payment from Merck and also is
eligible to receive contingent payments dependent upon the
achievement of certain developmental and regulatory approval
milestones. Any profits from the collaboration will be split
between the partners equally. Since licensed by Ridgeback, all
funds used for the development of molnupiravir have been provided
by Merck and Ridgeback.
Molnupiravir was evaluated in MOVe-OUT, a global Phase 3,
randomized, placebo-controlled, double-blind, multi-site study of
non-hospitalized adult patients with symptomatic,
laboratory-confirmed mild to moderate COVID-19 and at least one
risk factor associated with poor disease outcomes. The Phase 3
portion of the MOVe-OUT trial was conducted globally in more than
170 sites in locations including Argentina, Brazil, Canada, Chile,
Colombia, Egypt, France, Germany, Guatemala, Israel, Italy, Mexico,
Philippines, Poland, Russia, South Africa, Spain, Sweden, Taiwan,
Ukraine, the United Kingdom and the United States. For further
information about the MOVe-OUT trial, please visit
clinicaltrials.gov. Molnupiravir is also being evaluated for
post-exposure prophylaxis in MOVe-AHEAD, a global, multicenter,
randomized, double-blind, placebo-controlled Phase 3 study
evaluating the efficacy and safety of molnupiravir in preventing
the spread of COVID-19 within households. For more information,
please visit http://merckcovidresearch.com.
Please visit the Merck media library for molnupiravir images and
b-roll.
About Ridgeback Biotherapeutics
Headquartered in Miami, Florida, Ridgeback Biotherapeutics LP is
a biotechnology company focused on emerging infectious diseases.
Ridgeback markets EbangaTM for the treatment of Ebola and has a
late-stage development pipeline which includes molnupiravir for the
treatment of COVID-19. The team at Ridgeback is dedicated to
developing life-saving and life-changing solutions for patients and
diseases that need champions as well as providing global access to
these medicines. In line with Ridgeback’s mission for equitable
global access, all Ridgeback services and treatment for Ebola
patients in Africa are delivered free of charge.
About Merck
For over 130 years, Merck, known as MSD outside 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 candidates that
the candidates 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 2020
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 the Molnupiravir FDA Letter of Authorization at
https://www.merck.com/eua/Merck-EUA-letter.pdf,
Fact Sheet for Healthcare Providers, including Mandatory
Requirements for Administration of Molnupiravir under Emergency Use
Authorization, at https://www.merck.com/eua/molnupiravir-hcp-fact-sheet.pdf
and Fact Sheet for Patients and Caregivers at https://www.merck.com/eua/molnupiravir-patient-fact-sheet-english.pdf.
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version on businesswire.com: https://www.businesswire.com/news/home/20211224005081/en/
Media Contacts: Melissa Moody, (215) 407-3536 Courtney Ronaldo,
(908) 740-6132
Investor Contacts: Peter Dannenbaum, (908) 740-1037 Raychel
Kruper, (908) 740-2107
Ridgeback Media Contact: Chrissy Carvalho,
Chrissy@goldin.com
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