Merck Setback Limits Study of Covid Pill to Milder Disease
(Bloomberg) -- Merck & Co. halted development of two experimental drugs for patients hospitalized with Covid-19 and began a final trial of one of them, its highly anticipated antiviral pill, for people with milder disease after getting mixed results about the medicine’s benefits.
The pill known as molnupiravir reduced virus levels in patients during a mid-stage study but didn’t show a meaningful benefit in preventing hospitalizations and deaths, the Kenilworth, New Jersey-based company said in a statement. It decided to discontinue its development for the sickest patients, those hospitalized with the infection, after the trial showed it was unlikely to help them.
The drugmaker is also scrapping a therapy, MK-7110, that it acquired in a $425 million deal less than five months ago, marking another setback in its hunt to curb the pandemic after shutting down its vaccine program in January. It plans to focus on developing molnupiravir as an outpatient treatment, where there are few medicines available, after it showed signs of helping control the virus.
“We saw a very clear drug effect by measuring changes in the actual virus, a very clear dose effect, and an effect on viral load,” Roy Baynes, senior vice president and head of global clinical development at Merck, said of the findings from the outpatient trial. But with a limited number of participants enrolled, “the trial was not properly powered to adequately define the clinical benefit,” he said.
Merck shares closed up 0.3% to $76.66 in New York on Thursday.
Unfazed by the developments, infectious disease experts, public health officials and Wall Street analysts said they were eager to see more data on the drug’s performance in non-hospitalized patients.
“We still certainly need an oral antiviral to treat Covid-19,” said Rajesh Gandhi, an infectious disease physician at Massachusetts General Hospital and Harvard Medical School. “I hope the outpatient trial enrolls quickly so that we know one way or the other whether this drug will have a clinical benefit.”
Even as Covid-19 vaccines roll out around the world, the virus continues to pose a major public health threat, with new cases nearing record levels globally. Doctors have few effective treatments, and most are for the severely ill and require costly infusions.
Merck’s Covid hopes now rest solely with molunpiravir, a drug it bought the rights to from Miami-based partner Ridgeback Biotherapeutics last year.
On Thursday, the companies reported results from a trial of 302 patients with early symptoms of infection, comparing the effect of the antiviral to a placebo. Though fewer patients who received the drug were hospitalized or died than those on placebo, the limited number of cases meant there wasn’t enough information to provide a meaningful measure of clinical effect, the company said.
Nose and throat swabs taken from patients showed molnupiravir inhibited replication of the virus, a sign that its antiviral benefits may prevent hospitalizations and deaths in a larger trial, Baynes said. Merck and Ridgeback selected an 800 milligram dose of the drug to continue researching and will begin recruiting for a late-stage study in late April or early May.
The partners will approach the Phase 3 study differently, focusing on high-risk patients such as those with diabetes at an earlier stage of the disease -- within five days of developing symptoms. “The effect seems to be most likely in patients who have had the shortest duration of infection,” Baynes added.
Gandhi supported Merck’s path forward. “Our experience with antiviral therapeutics for other respiratory viral infections – like influenza – also supports the concept that the earlier, the better,” he said.
Should the Phase 3 trial succeed, Merck anticipates it could get the final data in September or October. Baynes said an interim analysis could come earlier, however, allowing it to get an emergency-use authorization before the end of the year. Merck executives had previously said it would be possible to seek clearance based on the mid-stage study.
Merck also tested molnupiravir in a trial of 304 hospitalized patients to assess whether it might hasten their recovery. The drugmaker ultimately concluded the pill was unlikely to have a clinical benefit and discontinued its development for the sickest patients.
It’s not entirely surprising the drug didn’t work in hospitalized patients, Baynes said. Since the drug prevents the virus from replicating, it’s more likely to work on patients in the earliest stages of the disease.
In all, Merck aimed to enroll 2,750 total participants spanning clinical sites in the U.S., Colombia, Israel and Russia, among others. Baynes said the pandemic posed challenges to recruitment. The findings, which have been shared with regulatory authorities, will be presented at an upcoming medical meeting.
Merck is looking to develop the first Covid antiviral that could be deployed broadly, given twice a day for five days. Pfizer Inc. and other drugmakers developing Covid pills are further behind.
At the start of the pandemic, Merck’s top scientists sifted through thousands of shelved compounds in hopes of finding a potential therapy to treat Covid, but “nothing materialized,” said Nicholas Kartsonis, senior vice president of clinical research for infectious diseases and vaccines at Merck Research Laboratories. So the drug giant took its search external.
In May, the company announced an agreement for exclusive worldwide rights to develop and commercialize molnupiravir and related molecules with Ridgeback. The biotechnology company, which had licensed the candidate from Emory only two months earlier, received an undisclosed payment and stands to share some of the profits should molnupiravir be approved.
Millions of Doses
Merck has the ability to make up to 100 million capsules -- or 10 million courses of treatment -- in 2021.
It has been uniquely challenging for scientists and drugmakers to develop Covid treatments. Viruses like SARS-CoV-2 hijack human cells and set up machinery inside of them to churn out copies of themselves. The goal is to stop the virus without harming the cells.
Molnupiravir is among a class of drugs known as nucleoside analogues that target the virus’s reproductive mechanism. It works by introducing errors into the virus’s RNA that are then replicated until it’s defunct.
While nucleoside analogues have sparked some concerns about safety, all three doses in the studies were “extremely well tolerated,” Baynes said. Still, a more substantial safety database will be needed to support an emergency-use filing for a drug that’s first in its class, he said.
Bloomberg Intelligence analysts Sam Fazeli andCinney Zhang said they were concerned that the highest-dose formulation of molnupiravir was being moved into the late-stage study, “raising questions about the side-effect profile as well as whether a higher dose would have provided even better efficacy.”
As for Merck’s other Covid therapy, MK-7110, the company said the intravenous drug wouldn’t have been available until the first half of 2022 based on the additional research required to prove that it works. That protracted timeline and the need to focus on molnupiravir were driving factors in abandoning development of the drug, the company said.
In late December, the U.S. agreed to pay Merck $356 million for 60,000 to 100,000 of doses of MK-7110. A spokesperson for the Department of Health and Human Services said purchase of the product had been contingent on an emergency-use authorization, and the unused funds will become available for other Covid-19 response needs.
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