By 
Merck has agreed to provide the U.S. government 3.1 million courses of molnupiravir, should regulators clear the pill for use.
Photo:
Merck
By
and
Updated Nov. 26, 2021 1:14 pm ET
& Co. and Ridgeback Biotherapeutics LP said a final analysis of their experimental Covid-19 pill found the drug less effective than an early look, prompting U.S. health regulators to continue a staff review of the drug’s application days before an outside panel meets.
The Food and Drug Administration made public Friday their initial review of the drug’s application, including an analysis of clinical-trial data for the drug, molnupiravir. Agency staff said the drug was effective at reducing the risk of hospitalization and death, but they didn’t take a position on whether the agency should authorize the drug. The agency also said no major safety concerns turned up in late-stage testing.
The FDA said it is still conducting its review of molnupiravir, after the companies told the agency earlier this week the pill was 30% effective in a final analysis of the late-stage study results. After taking an early look at results, the companies had reported in October that molnupiravir was 50% effective.
Molnupiravir, and another experimental antiviral from
Pfizer Inc.
that is also under FDA review, promise to fill a big gap in Covid-19 treatment for a pill that people could easily take at home to keep them out of the hospital.
How Molnupiravir Works
The drug interferes with SARS-CoV-2’s ability to reproduce within a patient’s cells.
How molnupiravir interferes with RNA replication
How viral reproduction works
New RNA is assembled by stringing together blocks of chemical units called bases.
CELL
BASES
1. The virus infiltrates a patient’s cells.
RNA
molnupiravir
The shape of the molnupiravir molecule resembles one of these bases. When the drug enters an infected cell, it is incorporated into the growing viral RNA strand.
VIRUS
RNA
2. It begins making copies of its RNA, which contains the genetic instructions for building new viruses.
This intrusion introduces errors into the virus’s genetic code, rendering the virus unable to make viable copies of itself.
3. Once an RNA molecule is complete, it gets packaged into a new viral coating and exported from the cell. These new copies go on to infect more cells.
How viral reproduction works
CELL
The virus infiltrates a patient’s cells.
It begins making copies of its RNA, which contains the genetic instructions for building new viruses.
VIRUS
RNA
Once an RNA molecule is complete, it gets packaged into a new viral coating and exported from the cell. These new copies go on to infect more cells.
How molnupiravir interferes with RNA replication
New RNA is assembled by stringing together blocks of chemical units called bases.
RNA
BASES
The shape of the molnupiravir molecule resembles one of these bases. When the drug enters an infected cell, it is incorporated into the growing viral RNA strand.
molnupiravir
This intrusion introduces errors into the virus’s genetic code, rendering the virus unable to make viable copies of itself.
How viral reproduction works
CELL
The virus infiltrates a patient’s cells.
It begins making copies of its RNA, which contains the genetic instructions for building new viruses.
VIRUS
RNA
Once an RNA molecule is complete, it gets packaged into a new viral coating and exported from the cell. These new copies go on to infect more cells.
How molnupiravir interferes with RNA replication
New RNA is assembled by stringing together blocks of chemical units called bases.
RNA
BASES
The shape of the molnupiravir molecule resembles one of these bases. When the drug enters an infected cell, it is incorporated into the growing viral RNA strand.
molnupiravir
This intrusion introduces errors into the virus’s genetic code, rendering the virus unable to make viable copies of itself.
Source: Timothy Sheahan,
University of North Carolina
Josh Ulick and Erik Brynildsen/
THE WALL STREET JOURNAL
So far, people at high risk of severe disease seeking to avoid hospitalization have usually had to go to a hospital or clinic that can inject or infuse an antibody drug.
The U.K. cleared molnupiravir for use earlier this month.
The latest molnupiravir efficacy rate is disappointing, but the drug could still be a helpful treatment because it will be more convenient and easier to access than the antibody drugs currently available, said Peter Chin-Hong, an infectious-disease specialist and professor of medicine at the University of California San Francisco. The antibody therapies often need to be administered via an infusion or injection at a hospital or clinic
“Thirty percent is still meaningful in a disease to prevent someone from being hospitalized,” Dr. Chin Hong said.
Antibody drugs from
Regeneron Pharmaceuticals Inc.
and from
PLC and its partner
Vir Biotechnology Inc.
were found in testing to cut the risk of hospitalization or death by at least 70%.
An experimental pill from Pfizer Inc., which is also under FDA review, cut the risk of hospitalization and death by about 89% in an early look at data. That rate could change after Pfizer performs a final analysis.
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FDA staff reviews are a routine part of the regulatory evaluation process before the agency decides whether to green light a product. Merck and Ridgeback requested emergency use authorization last month.
The drug’s clinical-trial performance will be discussed Tuesday when an outside panel of advisers to the FDA meets and votes whether to recommend the agency clear the drug for use.
The FDA isn’t required to follow the panel’s advice but normally does. Should the panel give a thumbs-up, an FDA decision could come before the end of the year.
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The agency hasn’t scheduled a meeting of the panel to review Pfizer’s drug, called Paxlovid.
Researchers designed molnupiravir to work by mucking up the virus’s ability to replicate, by introducing errors into its genetic code. A course of treatment is eight pills daily for five days, started within five days of showing symptoms.
In the documents it posted, the FDA said it became aware of the final analysis earlier this week and was still reviewing the data. The agency said its assessment, which was based on the interim analysis, might change, and that it would provide additional analysis when the panel meets Tuesday.
The FDA asked the panel to discuss the use of molnupiravir in pregnant women, who weren’t included in the late-stage Merck-Ridgeback trial.
The agency said Merck agreed that molnupiravir should not be authorized for people under 18 years of age. It also said the drug shouldn’t be cleared for use in hospitalized patients, after the drug failed to show benefit in a separate trial.
Some scientists have expressed concern about the safety of the drug and whether it might cause mutations in cells that are harmful to people.
Doctors are increasingly turning to monoclonal-antibody drugs to treat high-risk patients who get sick with Covid-19. WSJ takes a look at how the therapies work and why they’re important for saving lives. Illustration: Jacob Reynolds/WSJ
Mutations were seen when researchers exposed Chinese hamster ovary cells in a lab to the drug compound for 32 days, but Merck says its testing has found the drug safe for people. Merck said diarrhea and nausea were the most common side effects in trial subjects who took molnupiravir.
The company plans to manufacture 10 million courses of treatment by the end of the year and at least double that amount next year.
Merck has agreed to provide the U.S. government 3.1 million courses of molnupiravir for about $2.2 billion, should regulators clear the pill for use.
The Biden administration is expected to allocate the supply to states, which in turn will direct them to pharmacies, hospitals and doctor’s offices.
Write to Jared S. Hopkins at jared.hopkins@wsj.com and Betsy McKay at betsy.mckay+1@wsj.com
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Appeared in the November 27, 2021, print edition as ‘Merck’s Covid-19 Pill Was 30% Effective in Final Study.’
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