Phase 3 MOVe-OUT Study of Molnupiravir in
Outpatients to Proceed, Phase 2/3 MOVe-IN Study in Hospitalized
Patients Will Not Proceed
Merck (NYSE: MRK), known as MSD outside the United States and
Canada, and Ridgeback Biotherapeutics today provided an update on
the clinical development program for molnupiravir (MK-4482/
EIDD-2801), an investigational orally available antiviral
therapeutic. Based on a planned interim analysis of data from the
Phase 2, dose-finding portion (Part 1) of two ongoing
placebo-controlled Phase 2/3 trials evaluating molnupiravir
administered twice a day for five days in outpatients (MOVe-OUT)
and hospitalized patients (MOVe-IN) with COVID-19, and from a
previously completed Phase 2a dose-ranging study in outpatients,
the decision has been made to proceed with the Phase 3 portion
(Part 2) of MOVe-OUT in outpatients with COVID-19, evaluating the
800 mg dose of molnupiravir twice daily. Data from MOVe-IN indicate
that molnupiravir is unlikely to demonstrate a clinical benefit in
hospitalized patients, who generally had a longer duration of
symptoms prior to study entry; therefore, the decision has been
made not to proceed to Phase 3.
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“We continue to make progress in the clinical development of our
antiviral candidate molnupiravir. Data from the dose-finding
portion of these studies are consistent with the mechanism of
action and provide meaningful evidence for the antiviral potential
of the 800 mg dose,” said Dr. Roy Baynes, senior vice president and
head of global clinical development, chief medical officer, Merck
Research Laboratories. “Based on the findings of this study we are
advancing a Phase 3 trial program in non-hospitalized patients that
strategically leverages our large network of clinical sites to
enroll appropriate patients globally.”
“We are pleased that molnupiravir continues to show promise as a
potential treatment for non-hospitalized patients with COVID-19,”
said Wendy Holman, Chief Executive Officer, Ridgeback
Biotherapeutics. “Data from Ridgeback Bio’s EIDD-2801-2003 study
(MK-4482-006) coupled with Merck’s MK-4482-002 study provide
compelling evidence for the antiviral activity of molnupiravir. We
look forward to the initiation and completion of the Phase 3
portion of the MOVe-OUT study.”
Update on MOVe-OUT (MK-4482-002) and MOVe-IN
(MK-4482-001)
MOVe-OUT is an ongoing Phase 2/3, randomized,
placebo-controlled, double-blind, multi-site study evaluating the
efficacy, safety and pharmacokinetics of orally administered
molnupiravir in non-hospitalized participants with COVID-19
confirmed using polymerase chain reaction. The primary efficacy
objective of MOVe-OUT is to evaluate the efficacy of molnupiravir
compared to placebo as assessed by the percentage of patients who
are hospitalized and/or die from the time of randomization through
Day 29. Part 1 of MOVe-OUT enrolled a total of 302 participants,
with symptom onset within seven days prior to randomization, who
were assigned to receive molnupiravir 200 mg (75), 400 mg (77), or
800 mg (76), or placebo (74).
The percentage of patients who were hospitalized and/or died in
Part 1 of the MOVe-OUT study was lower in the combined
molnupiravir-treated groups versus the placebo arm; the number of
events reported are not sufficient to provide a meaningful measure
of clinical effect. Analysis of SARS-CoV-2 in nasopharyngeal and
oropharyngeal swabs from patients in both MOVe-OUT and MOVe-IN
using quantitative and qualitative polymerase chain reaction, an
exploratory endpoint, indicated that molnupiravir inhibits
replication of the virus, as demonstrated by a greater decrease
from baseline in viral RNA compared to placebo at Day 5 and Day 10,
and by a larger proportion of participants with undetectable viral
RNA at Day 10 and Day 15 following the end of treatment. The
largest overall magnitude of antiviral effect was observed in the
800 mg dose compared with the 200 mg and 400 mg doses. These
differences in virology endpoints were more pronounced in
participants enrolled < 5 days
following symptom onset.
Among 299 patients who received at least one dose of study
intervention in MOVe-OUT, 6.2% (14/225) of those receiving
molnupiravir and 6.8% (5/74) of those receiving placebo reported
drug-related adverse events. In MOVe-IN, of 293 patients who
received at least one dose of study intervention, 11.0% (24/218) of
those treated with molnupiravir and 21.3% (16/75) of those
receiving placebo reported drug-related adverse events. To date,
safety and laboratory data from MOVe-IN and MOVe-OUT provide no
evidence for unexpected findings or trends observed at any of the
doses studied. In both trials, no deaths were considered
drug-related by the investigators, and there were no drug-related
adverse events that led to discontinuation in participants who
received molnupiravir. Interim results from both MOVe-IN and
MOVe-OUT, including virology findings and pharmacokinetic analyses,
have been shared with regulatory authorities and will be presented
at an upcoming medical meeting.
The external Data Monitoring Committee noted that the subgroup
analyses support potential benefit of treatment and suggested
amendments to the MOVe-OUT protocol to focus enrollment on patients
early in the course of disease and those considered high risk for
poor COVID-19 outcomes (e.g., older patients, those with obesity
and diabetes). Based upon these recommendations, Merck will amend
the inclusion criteria for MOVe-OUT by reducing the allowable
symptom duration for enrollment to < 5 days and by enrolling participants with at
least one risk factor for progression to severe disease. Merck
plans to start enrolling patients in Phase 3 portion (Part 2) of
MOVe-OUT by late April/early May.
Final data from the Phase 3 portion (Part 2) of the MOVe-OUT
study is estimated to be available in September/ October 2021.
Merck currently anticipates that, pending favorable results from
MOVe-OUT, the earliest possible submission for an Emergency Use
Authorization for molnupiravir will be in the second half of 2021.
Merck and Ridgeback Biotherapeutics plan to share further findings
from the ongoing molnupiravir development program with regulatory
agencies as they become available.
In addition, Merck plans to initiate a clinical program to
evaluate molnupiravir for post- exposure prophylaxis in the second
half of 2021.
About the MOVe-OUT study design
MOVe-OUT (MK-4482-002) is a Phase 2/3, randomized,
placebo-controlled, double-blind, multi-site study evaluating the
efficacy, safety and pharmacokinetics of orally administered
molnupiravir in non-hospitalized participants at least 18 years of
age with laboratory confirmed COVID-19 and symptom onset within
seven days prior to randomization. The trial plans to enroll a
total of 1850 participants with mild or moderate COVID-19. The
Phase 2 portion of the trial enrolled 302 participants randomized
1:1:1:1 to receive molnupiravir 200 mg, 400mg, 800mg or placebo
twice daily for 5 days. The primary efficacy objective is to
evaluate efficacy of molnupiravir compared to placebo as assessed
by the percentage of participants who are hospitalized and/or die
during the period from randomization through Day 29. Exploratory
endpoints supporting dose selection for Phase 3 portion (Part 2)
include change from baseline in SARS-CoV-2 RNA plasma levels and
percentage of participants with undetectable SARS-CoV-2 RNA various
time points, viral RNA mutation rate as assessed by comparison of
baseline and post-baseline virus sequencing and pharmacokinetic
data (eg, Ctrough, Cmax, tmax, t1/2, AUC0-12). Following the
completion of Part 1 the inclusion criteria for MOVe-OUT were
amended reducing the allowable symptom duration for enrollment to
< 5 days and increasing enrollment
for those considered high risk for poor COVID-19 outcomes (e.g.,
older patients and those with obesity and diabetes). For further
information regarding the trial please visit
clinicaltrials.gov.
About the MOVe-IN study design
MOVe-IN (MK-4482-001) was a Phase 2/3, randomized,
placebo-controlled, double-blind, multi-site trial evaluating the
efficacy, safety, and pharmacokinetics of orally administered
molnupiravir in hospitalized participants at least 18 years of age
with laboratory confirmed COVID-19 and symptom onset within 10 days
prior to randomization. The Phase 2 portion of the trial enrolled
304 participants randomized 1:1:1:1 to who received molnupiravir
200 mg, 400 mg, 800 mg or placebo twice daily for 5 days. The
primary efficacy endpoint was to evaluate the efficacy of
molnupiravir compared to placebo as assessed by the rate of
sustained recovery from randomization through Day 29. Exploratory
endpoints supporting dose selection for the Phase 3 portion (Part
2) of the trial included change from baseline in SARS-CoV-2 RNA
levels and percentage of participants with undetectable SARS-CoV-2
RNA at various time points, viral RNA mutation rate as assessed by
comparison of baseline and post-baseline virus sequencing and
pharmacokinetic data (eg, Ctrough, Cmax, tmax, t1/2, AUC0-12).
Following an interim analysis of data, it was concluded that the
study was unlikely to demonstrate a clinical benefit in
hospitalized patients. The decision was made to discontinue the
study.
About Molnupiravir Protocol MK-4482-006 (also known as
EIDD-2801-2003)
Protocol 6 (MK-4482-006) is a Phase 2a, double-blind,
placebo-controlled, randomized trial designed to compare the
safety, tolerability, and antiviral activity of molnupiravir versus
placebo as measured by viral RNA detection in symptomatic,
outpatient (at baseline) adults at least 18 years old with
SARS-CoV-2 infection as confirmed by viral RNA detection within
seven days of symptom onset. Of 202 treated participants,
molnupiravir was considered generally well tolerated and of the 4
serious adverse events reported, none were considered study drug
related. Preliminary data from this study was previously presented
at CROI 2021.
About Molnupiravir Nonclinical studies
Merck has conducted a comprehensive nonclinical program to
characterize the safety profile of molnupiravir. This program
included assays such as Big Blue and PIG-a which are designed to
provide a robust measure of a drug or chemical’s ability to induce
mutations in vivo. Animals were administered molnupiravir for
longer and at higher doses (mg/Kg) than those employed in human
studies. The totality of the data from these studies indicates that
molnupiravir is not mutagenic or genotoxic in in vivo mammalian
systems.
About Molnupiravir
Molnupiravir (EIDD-2801/MK-4482) is an investigational, orally
administered form of a potent ribonucleoside analog that inhibits
the replication of multiple RNA viruses including SARS-CoV-2, the
causative agent of COVID-19. Molnupiravir has been shown to be
active in several preclinical models of SARS-CoV-2, including for
prophylaxis, treatment, and prevention of transmission, as well as
SARS-CoV-1 and MERS. Molnupiravir was invented at Drug Innovations
at Emory (DRIVE), LLC, a not-for-profit biotechnology company
wholly owned by Emory University. For more information on
molnupiravir clinical trials please visit
https://merckcovidresearch.com/
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. Development of molnupiravir is entirely
funded by Ridgeback Biotherapeutics and Merck & Co., Inc. All
equity capital in Ridgeback Biotherapeutics, LP originated from
Wayne and Wendy Holman, who are committed to investing in and
supporting medical technologies that will save lives. The team at
Ridgeback is dedicated to working toward finding life-saving and
life-changing solutions for patients and diseases that need
champions.
About Merck
For 130 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.
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