Based on Prespecified Exploratory Endpoints,
a Lower Proportion of Participants Treated With LAGEVRIO Had an
Acute Care Visit Compared to Those Who Received Placebo
Based on a Post Hoc Analysis, Fewer Required
Respiratory Interventions (Including Invasive Mechanical
Ventilation)
Merck, known as MSD outside the United States and Canada, and
Ridgeback Biotherapeutics today announced the Annals of Internal
Medicine has published additional data from the Phase 3 MOVe-OUT
trial evaluating LAGEVRIO™ (molnupiravir), an investigational oral
antiviral medicine, in non-hospitalized adults with mild to
moderate COVID-19 who were at high risk for progressing to severe
disease.
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Analyses of pre-specified exploratory endpoints indicate that a
lower proportion of LAGEVRIO-treated participants in the modified
intent-to-treat (MITT) population had an acute care visit or a
COVID-19-related acute care visit versus placebo-treated
participants in the MITT population: 7.2% of participants who
received LAGEVRIO reported an acute care visit through Day 29,
versus 10.6% of placebo participants, with a relative risk
reduction [RRR] of 32.1% [CI, 4.4% to 51.7%]; 6.6% of participants
who received LAGEVRIO reported a COVID-19-related acute care visit,
versus 10.0% of placebo participants, with a RRR of 33.8% [CI, 5.6%
to 53.6%]. The MITT population included all participants who were
randomly assigned, received at least one dose of study drug, and
were not hospitalized before the first dose of study drug. Based on
a post hoc analysis, fewer LAGEVRIO-treated participants in the
MITT population required respiratory interventions (including
conventional oxygen therapy, a high-flow heated and humidified
device, noninvasive mechanical ventilation, or invasive mechanical
ventilation) versus placebo-treated participants, with a RRR of
34.3% [95% CI, 4.3% to 54.9%] for all respiratory interventions.
Based on additional post hoc analyses, participants in the safety
population who received LAGEVRIO showed earlier and larger
reductions in mean C-reactive protein (CRP) values, and earlier and
larger improvements in mean change from baseline oxygen saturation
(SpO2) values, compared with participants who received placebo. The
safety population consisted of all participants who had undergone
randomization and had received at least one dose of LAGEVRIO.
Post hoc analyses also suggest that among the subgroup of
participants who were hospitalized after randomization in MOVe-OUT,
the median time to hospital discharge was nine days [CI, 7 to 12
days] for participants who received LAGEVRIO, versus 12 days [CI, 9
to 14 days] in the placebo group. Consistent with the full MITT
population data, post hoc analyses also suggest that fewer
LAGEVRIO-treated participants who were hospitalized after
randomization required respiratory interventions versus
placebo-treated participants, with a RRR of 21.3% [95% CI, 0.2% to
38.0%] for all respiratory interventions.
“The analyses add to our understanding of the clinical profile
of LAGEVRIO and help to reinforce the importance of LAGEVRIO as
part of the response to the COVID-19 pandemic,” said Dr. Dean Y.
Li, president, Merck Research Laboratories.
“The primary data from MOVe-OUT demonstrated a significant
reduction in the risk for progression to severe COVID-19, including
hospitalization and death, when compared to placebo among
non-hospitalized, at-risk patients. In light of the continued
burden of COVID-19, we are encouraged by these new data,” said
Wendy Holman, chief executive officer, Ridgeback Biotherapeutics.
“We look forward to continuing to study LAGEVRIO with the goal of
helping high-risk patients and overburdened healthcare systems
globally continue to combat the COVID-19 pandemic.”
In addition to the MOVe-OUT trial, LAGEVRIO is 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 LAGEVRIO in preventing the
spread of COVID-19 within households.
About the MOVe-OUT Study
The Phase 3 MOVe-OUT clinical trial (NCT04575597) evaluated
LAGEVRIO (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 was to evaluate the efficacy of
LAGEVRIO 800 mg twice-daily for five days compared to placebo as
assessed by the percentage of participants who were hospitalized
and/or died through Day 29. These findings were published in the
New England Journal of Medicine.
In analyses from all randomized patients (n=1433) in the MITT
population, LAGEVRIO reduced the risk of hospitalization or death:
9.7% (68/699) of patients in the placebo group were hospitalized or
died through Day 29 compared to 6.8% (48/709) of patients who
received LAGEVRIO, for an absolute risk reduction of 3.0% (95%
confidence interval [CI]: 0.1, 5.9). Nine deaths were reported in
the placebo group, and one in the LAGEVRIO group.
The determination of primary efficacy was based on a planned
interim analysis of 762 participants. At the interim analysis,
treatment with LAGEVRIO significantly reduced the risk for
hospitalizations and death through Day 29 following randomization:
14.1% (53/377) of patients in the placebo group were hospitalized
or died, compared to 7.3% (28/385) of patients who received
LAGEVRIO. The absolute risk reduction between the LAGEVRIO and the
placebo arm was 6.8 percentage points (95% CI: 2.4, 11.3;
p=0.0024).
The safety of LAGEVRIO was evaluated based on an analysis of
MOVe-OUT in which 1,411 non-hospitalized subjects with COVID-19
were randomized and treated with LAGEVRIO (N=710) or placebo
(N=701) for up to 5 days. Adverse events were those reported while
subjects were on study intervention or within 14 days of study
intervention completion/discontinuation. The most common adverse
reactions for LAGEVRIO (incidence ≥1%) were diarrhea (2% for
LAGEVRIO, 2% for placebo), nausea (1% for LAGEVRIO, 1% for placebo)
and dizziness (1% for LAGEVRIO, 1% for placebo). Discontinuation of
study intervention due to an adverse event (AE) occurred in 1% of
subjects receiving LAGEVRIO and 3% of subjects receiving placebo.
Serious AEs occurred in 7% of subjects receiving LAGEVRIO and 10%
receiving placebo; most serious AEs were COVID-19 related.
About Merck’s Global Efforts to Accelerate Access to LAGEVRIO
(molnupiravir) Following Regulatory Authorizations or
Approvals
Global access has been a priority for Merck and Ridgeback since
the inception of their LAGEVRIO collaboration. The companies are
committed to providing timely access to LAGEVRIO globally through
our comprehensive supply and access approach, which includes:
Supply: As of May 31, 2022, Merck has supplied more than
8 million courses of treatment to governments in more than 30
markets worldwide.
Voluntary licenses: As part of its commitment to
widespread global access, Merck granted voluntary licenses (VLs) to
generics manufacturers and to the Medicines Patent Pool to make
generic molnupiravir available in more than 100 low- and
middle-income countries following approvals or emergency
authorization by local regulatory agencies. Through our VL
agreements with generics manufacturers, more than 3 million courses
of generic molnupiravir have been delivered to approximately 15
markets through March 2022.
UNICEF: To supplement the supply from licensed generic
manufacturers, Merck has entered into an agreement with UNICEF to
allocate up to 3 million courses of LAGEVRIO to low- and
middle-income countries through the first half of 2022. Merck has
also committed 2 million patient courses of LAGEVRIO, available to
USAID at Merck’s best access price to increase access in
lower-income countries.
Product donation: Merck has donated 100,000 courses of
therapy to Direct Relief, a global humanitarian aid organization,
for distribution to refugees in low- and middle-income countries,
including 50,000 courses of therapy for people affected by the
invasion of Ukraine.
Purchase and supply agreements: Merck entered into a
procurement agreement with the U.S. government under which the
company supplied approximately 3.1 million courses of LAGEVRIO to
the U.S. government, upon Emergency Use Authorization from the U.S.
Food and Drug Administration. The U.S. Department of Health and
Human Services (HHS) has created a public website to identify
locations that have received shipments of government-procured
COVID-19 therapeutics, including LAGEVRIO, available under
Emergency Use Authorization. HHS has also created a Test-to-Treat
locator to help identify pharmacies and community health centers
across the nation where people can get tested for COVID-19 and
receive appropriate treatments, as needed.
Merck has also entered into additional advance purchase and
supply agreements for LAGEVRIO with governments of more than 30
markets worldwide, and is currently in discussions with additional
governments. Merck is implementing a tiered pricing approach based
on World Bank country income criteria to reflect countries’
relative ability to finance their health response to the
pandemic.
Merck continues to discuss additional measures and
collaborations to accelerate broad, global access to LAGEVRIO.
Authorized Use of LAGEVRIO in the U.S.
The U.S. Food and Drug Administration (FDA) has issued an EUA
for the emergency use of the unapproved product LAGEVRIO, 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 approved or authorized
by FDA are not accessible or clinically appropriate. LAGEVRIO is
not FDA-approved for any use including for use for the treatment of
COVID-19.
The emergency use of LAGEVRIO is only authorized for the
duration of the declaration that circumstances exist justifying the
authorization of the emergency use of drugs and biological products
during the COVID-19 pandemic under Section 564(b)(1) of the Federal
Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b)(1) unless the
declaration is terminated or authorization revoked sooner.
LAGEVRIO is not authorized for use in patients less than 18
years of age or for initiation of treatment in patients
hospitalized due to COVID-19. Benefit of treatment with LAGEVRIO
has not been observed in subjects when treatment was initiated
after hospitalization due to COVID-19. LAGEVRIO is not authorized
for use for longer than five consecutive days. LAGEVRIO is not
authorized for pre-exposure or post-exposure prophylaxis for
prevention of COVID-19. LAGEVRIO 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 LAGEVRIO belongs (i.e., anti-infectives).
Selected Safety Information for LAGEVRIO
Contraindications
No contraindications have been identified based on the limited
available data on the emergency use of LAGEVRIO authorized under
this EUA.
Warnings and Precautions
There are limited clinical data available for LAGEVRIO. Serious
and unexpected adverse events may occur that have not been
previously reported with LAGEVRIO use.
LAGEVRIO is not recommended for use during pregnancy. Based on
findings from animal reproduction studies, LAGEVRIO may cause fetal
harm when administered to pregnant individuals. There are no
available human data on the use of LAGEVRIO in pregnant individuals
to evaluate the risk of major birth defects, miscarriage or adverse
maternal or fetal outcomes.
LAGEVRIO 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 LAGEVRIO during pregnancy, the prescribing
healthcare provider must document that the known and potential
benefits and the potential risks of using LAGEVRIO during pregnancy
were communicated to the pregnant individual.
There is a pregnancy surveillance program that monitors
pregnancy outcomes in individuals exposed to LAGEVRIO 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 LAGEVRIO 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 LAGEVRIO and for 4
days after the final dose.
Prior to initiating treatment with LAGEVRIO, assess whether an
individual of childbearing potential is pregnant or not, if
clinically indicated.
Hypersensitivity reactions, including anaphylaxis, have been
reported with LAGEVRIO. If signs and symptoms of a clinically
significant hypersensitivity reaction or anaphylaxis occur,
immediately discontinue LAGEVRIO and initiate appropriate
medications and/or supportive care.
LAGEVRIO 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 LAGEVRIO have not been established in
pediatric patients.
Adverse Reactions
The most common adverse reactions occurring in ≥1% of subjects
in the LAGEVRIO 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
LAGEVRIO 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 LAGEVRIO 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 LAGEVRIO. No clinical
drug-drug interaction trials of LAGEVRIO 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
LAGEVRIO, breastfeeding is not recommended during treatment with
LAGEVRIO 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 LAGEVRIO.
Males of Reproductive Potential
Nonclinical studies to fully assess the potential for LAGEVRIO
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 the
last dose of LAGEVRIO. The risk beyond three months after the last
dose of LAGEVRIO is unknown.
Required Reporting for Serious Adverse Events and Medication
Errors
The prescribing healthcare provider and/or the provider’s
designee is/are responsible for mandatory reporting of all serious
adverse events and medication errors potentially related to
LAGEVRIO 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 LAGEVRIO (molnupiravir)
LAGEVRIO (molnupiravir) (MK-4482) is an investigational, orally
administered nucleoside analog that inhibits the 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 as LAGEVRIO.
Results from the Phase 3 MOVe-OUT study demonstrated the
efficacy benefit of LAGEVRIO treatment was generally consistent
across patients infected with SARS-CoV-2 variants of concern,
Delta, Gamma and Mu. Preclinical data has shown that LAGEVRIO has
antiviral activity against the variant, Omicron (B1.1.529).
LAGEVRIO 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. LAGEVRIO 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 LAGEVRIO have been provided by
Merck and Ridgeback.
LAGEVRIO 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
At Merck, known as MSD outside of the United States and Canada,
we are unified around our purpose: We use the power of leading-edge
science to save and improve lives around the world. For more than
130 years, we have brought hope to humanity through the development
of important medicines and vaccines. We aspire to be the premier
research-intensive biopharmaceutical company in the world – and
today, we are at the forefront of research to deliver innovative
health solutions that advance the prevention and treatment of
diseases in people and animals. We foster a diverse and inclusive
global workforce and operate responsibly every day to enable a
safe, sustainable and healthy future for all people and
communities. 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., Rahway,
N.J., USA
This news release of Merck & Co., Inc., Rahway, 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 Annual
Report on Form 10-K for the year ended December 31, 2021 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20220607005398/en/
Media Contacts:
Melissa Moody (215) 407-3536
Courtney Ronaldo (908) 740-6132
Ridgeback Media Contact:
Chrissy Carvalho Chrissy@goldin.com
Investor Contacts:
Peter Dannenbaum (908) 740-1037
Damini Chokshi (908) 740-1807
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