Merck’s pill designed to treat Kovid-19 succeeds in major study

The companies said on Friday that the pill reduced the risk of hospitalization or death by nearly 50% in study subjects with mild to moderate COVID-19.

The drug, called molnupiravir, was performing so well in its final phase trials that Merck and Ridgeback said they stopped enrolling subjects after discussions with the US Food and Drug Administration.

The results put mollupiravir on track to potentially authorize by the end of the year and finally provide an alternative for doctors who have spent the pandemic looking for a drug that infected people can easily take at home. so that they can be prevented from being admitted to the hospital.

Chief Executive Rob Davis said Merck plans to ask the FDA to authorize use of the drug in the coming weeks.

If approved by regulators, the drug would be the first oral antiviral for COVID-19. Within five days of symptoms appearing, people would take eight pills daily for five days if they followed the same protocol used in the study.

Molnupiravir will become a type of Tamiflu for Covid-19, a drug that can be given to patients when they first develop symptoms, slowing the spread of the virus in the body and potentially making people seriously ill. prevent it from happening.

“The ability to take a devastating disease like COVID-19 and potentially make it a manageable condition through a very convenient round of administration, which is an oral pill that you can take at home, for the potential has significant implications for managing the ongoing pandemic,” Mr Davis said.

Along with vaccines, the pill, if authorized, would help transform COVID-19 from a deadly pandemic disease that turns hospitals into a treatable disease as it becomes endemic in the population. “It will help to reach that endemic level and maintain that level,” said Gabor Kellen, director of the department of emergency medicine at Johns Hopkins Medicine.

Doctors expressed concern, however, that the pill’s promising results may encourage people who are hesitant to get vaccinated and feel excited about not getting vaccinated.

“Vaccination is still, first and foremost, the most effective and least risky thing you can do,” said John Mailers, chairman of the Division of Infectious Diseases at the University of Pittsburgh Medical Center and the University of Pittsburgh.

Merck and Ridgeback reported the findings in a press release after an initial look at the study’s results that ended in November. The results have not been published in a peer-reviewed scientific journal.

The companies said the rate of side effects in study subjects who received mollupiravir and those who received a placebo were similar, although they did not say in their news release whether the drug was found to be safe in the study. However, Mr Davis said he had confidence in the drug’s safety profile.

The drug appeared to be effective against transmitting COVID-19 variants, including the highly infectious Delta, according to the companies.

The result is Kenilworth, NJ-based Merck, one of the world’s largest drugmakers, to play a bigger role in responding to the pandemic after several setbacks. After two of its experimental vaccines failed trials, Merck agreed to help manufacture Johnson & Johnson’s shot. Merck also halted development of an experimental drug it acquired through a $425 million purchase.

According to Diana Grebosch, an analyst at Leerink LLC, mollupiravir could generate $10 billion in sales cumulatively by 2025, given the potential for stockpiling and its ability to prevent COVID-19, which is still being studied. Is. Merck shares rose more than 9% on the Pill News.

Merck said it expects to have 10 million courses of treatment ready by the end of the year, and expects more doses to arrive next year. If authorized, Merck would start shipping the dose very quickly, Mr Davis said.

The US has agreed to pay Merck $1.2 billion for 1.7 million courses of treatment to regulators using mollupiravir’s green light.

Merck said it plans to make the drug available worldwide and has license agreements with generic manufacturers to make the drug available to low-income countries, many of which have access to vaccines to slow the spread of the virus. Difficulty reaching.

Vaccines are the main weapon for fighting epidemics, but doctors and health officials have long sought drugs that can help keep people who become infected from developing serious illness and requiring hospitalization.

Nearly two years into the pandemic, however, drug options are limited. Remdesivir, Gilead Sciences Inc., GILD -1.54% is the only antiviral fully approved by the FDA, but is only used to treat hospitalized patients.

FDA Regeneron Pharmaceuticals Inc. and have approved antibody drugs made by companies such as GlaxoSmithKline Plc and its affiliate Vir Biotechnology Inc. for people with mild to moderate COVID-19 who are not hospitalized. The drugs reduced the risk of hospitalization or death by at least 70% in their trials, a higher efficacy rate than mollupiravir. Yet antibody drugs are more complex to administer than swallowing a pill, requiring an intravenous infusion, which initially slowed their uptake.

One of the more effective drugs against COVID-19, a steroid called dexamethasone, is for very ill patients.

“Even if the pill on its face showed less benefit than monoclonal antibodies because it would be so easy to use, it would have a huge impact globally,” said Daniel Kuritzks, head of the division. Infectious Diseases at Brigham and Women’s Hospital in Boston.

Dr. Mellors said the companies’ results were encouraging, as well as leaving them with questions about how effective the drug is in vaccinated people with breakthrough infections and how its effectiveness compares with monoclonal antibodies. “We need to look at the full data set,” he said. It will also be important to study the drug’s safety over the long term, he added.

Rajesh Gandhi, an infectious disease physician at Massachusetts General Hospital and Harvard Medical School, said he would like to know whether the pill actually shortens the duration of symptoms and reduces disease severity for patients who were hospitalized.

He said that if the drug is authorized and when more data becomes available, he will prescribe the drug to outpatients with no risk factors, and antivirals are best, in line with the group studied by Merck and Ridgeback, rather than those at low risk. Early in the course of an illness. Still, he said the drug would be helpful for people at risk for serious illness.

“You could call in a prescription for the patient, they wouldn’t have to come in to get an infusion or a subcutaneous injection, and so that would make it easier, like how we treat influenza during flu season, ” They said.

Molnupiravir was initially developed by a non-profit biotechnology company owned by Emory University. Ridgeback licensed and collaborated with Emory in early 2020, and later announced a partnership with Merck.

Molnupiravir works by attacking a different part of the virus than the spike protein on the coronavirus typically targeted by COVID-19 vaccines and other COVID-19 drugs. The part attacked by mollupiravir helps the virus to reproduce.

“You now have an oral, easily accessible, easily delivered drug to keep people out of the hospital and keep them from dying,” said Wayne Holman, co-founder of Miami-based Ridgeback.

Other companies are also developing COVID-19 antivirals, including Pfizer Inc., as well as Roche Holding AG and Aetia Pharmaceuticals Inc.

After researchers found that it failed to help them and is unlikely to reduce hospital stays and deaths, Merck and Ridgeback halted a study of mollupiravir in hospitalized patients in April.

The companies continued to study whether the antiviral was effective during the course of the disease and in people who are at high risk of COVID-19 complications. According to doctors and scientists, antivirals are most effective when taken soon after infection and become less beneficial over time as patients become ill.

The Merck-Ridgeback late-stage, or phase 3, study enrolled more than 1,400 people who were at high risk of becoming seriously ill with COVID-19. About half received an 800-milligram dose of mollupiravir twice a day for five days, while the other participants received a placebo.

High risk was defined as having at least one characteristic associated with serious illness or death, such as older age, obesity or diabetes. Treatment began within five days after participants developed COVID-19 symptoms.

In the interim analysis, 28 of the 385 subjects who received the drug were hospitalized after 29 days, Merck and Ridgeback said, compared to 53 of the 377 subjects in the placebo group who were either hospitalized. Or they had died, resulting in an efficacy rate of nearly that. 50%.

According to the companies, none of the subjects receiving mollupiravir had died over the course of 29 days, compared to eight deaths in the placebo group.

An interim review of the drug’s effectiveness and safety was conducted by an external panel of independent experts, known as the Data-Safety Monitoring Committee, which then shared its findings with Merck and Ridgeback.

The panel met late Tuesday to review the data, and then recommended stopping enrollment of the study because of the positive results, Dr. Holman said. The companies went to the FDA with that recommendation.

Mr Davis said researchers would still do a final analysis, which could mean the efficacy percentage has been adjusted but should not change the overall positive result.

Merck and Ridgeback said in September that they had launched a separate trial to study whether mollupiravir could prevent infection in people after exposure to the virus.