Inside the race to find a COVID-19 treatment pill – fr

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Inside the race to find a COVID-19 treatment pill – fr


An experimental COVID-19 treatment pill, called molnupiravir and under development by Merck & Co Inc and Ridgeback Biotherapeutics LP, can be seen in this undated photo released by Merck & Co Inc and obtained by Reuters on May 17, 2021. Merck & Co Inc / Document to be distributed via REUTERS

In early 2020, as a deadly new coronavirus began to spread around the world, Pfizer Inc (PFE.N) assembled what it called a “SWAT team” of scientists and chemists to identify a potential treatment to fight against COVID-19.

The US pharmaceutical giant, which had started exploring a vaccine, also wanted to produce a pill that could stop the infection from progressing, much like the widely used drug Tamiflu fights the flu. The team scoured Pfizer’s molecule library for unused compounds to help jumpstart the process and quickly identified a promising candidate.

More than a year later, Pfizer has yet to undertake large-scale human trials of oral COVID-19 treatment – something it hopes to start by July.

Pfizer and rivals, including U.S.-based Merck & Co Inc (MRK.N) and Swiss pharmaceutical company Roche Holding AG (ROG.S), are rushing to produce the first antiviral pill people could take at the first signs of disease. Their common goal: to fill a key treatment gap by helping people recently infected with coronavirus avoid becoming seriously ill and having to be hospitalized.

But after almost 18 months of the pandemic, there is still no easy-to-administer treatment that has been shown to be effective against COVID-19, the disease caused by the coronavirus. This is despite the development of a number of effective COVID-19 vaccines, including one from Pfizer and its German partner BioNTech SE, which in December became the first to obtain authorization for use in the United States.

Pfizer’s experience highlights the challenges drug manufacturers face in developing an oral treatment for the virus. Unlike a vaccine, which only needs to trigger the body’s immune system, an effective antiviral pill must prevent a virus from spreading throughout the body while being selective enough to avoid interfering with healthy cells.

Testing antivirals is also difficult, according to drug company executives. A drug must be given early in an infection, which means finding trial participants who have recently contracted COVID-19. Many people infected with the virus only develop mild symptoms, but studies need to prove that a drug has a significant impact on the health of patients.

Pfizer CEO Albert Bourla said the company could seek emergency clearance in the United States for a COVID-19 pill as soon as the end of this year.

“Right now we have very good reason to believe that we can be successful,” Bourla said at an economic forum in Greece via video conference last week.

Pfizer and its rivals say the development process has been much faster than the several years it typically takes to produce a drug that can be taken in pill form.

Merck and Roche recently started late stage human trials and also said their drugs could be ready later this year. Merck is developing its drug in partnership with Ridgeback Biotherapeutics LP and Roche is working with Atea Pharmaceuticals Inc (AVIR.O).

Governments around the world have invested billions of dollars in vaccine development, but Pfizer, Merck and Roche say they have not received government funding to develop oral antivirals for the disease.

‘HUNT THE NEXT TAMIFLU’

While the rate of new COVID-19 infections is currently declining in some countries, others continue to fight the rapid spread of the virus. And with vaccine shortages in many countries, much of the world will not be vaccinated for several years. Many people are also reluctant to get vaccinated.

Scientists predict that COVID-19 – which has killed more than 3.5 million people worldwide – could turn into a seasonal flu-like illness.

“We need a pill that can keep people out of the hospital,” said Dr Rajesh Gandhi, professor and infectious disease specialist at Harvard Medical School.

Doctors have tried a number of existing oral drugs to fight COVID-19, but none of them have yet passed rigorous clinical tests.

Currently, the only treatments that help COVID-19 patients avoid hospitalization are antibody drugs that require long intravenous infusions and work less well against variants of the coronavirus.

Pfizer and rivals say their oral antiviral candidates could be effective against a wide range of coronavirus variants, but no relevant data has been made public.

For patients already hospitalized with COVID-19, treatment often involves steroids or anti-inflammatory drugs to manage symptoms of the infection, but these drugs do not target the virus itself. The only antiviral drug approved in the United States to treat COVID-19 is remdesivir from Gilead Sciences Inc., which is administered intravenously and used only for hospital patients.

Gilead is currently testing an inhaled form of remdesivir and is exploring other compounds that may be effective oral agents.

“We’re all on the hunt for the next Tamiflu,” Gilead Chief Medical Officer Merdad Parsey said.

Tamiflu is recommended for people who have had the flu for no more than two days and has been shown to shorten the duration of flu symptoms.

“MASTERPIECE OF CHEMISTRY”

Scientists and chemists at Pfizer began researching an antiviral treatment in January of last year. They quickly focused on a compound from 2003, when the company sought a cure for the world’s first SARS pandemic, said Charlotte Allerton, head of drug design at Pfizer.

The compound belongs to a class known as protease inhibitors, designed to block a key enzyme, or protease, essential for the coronavirus’s ability to multiply. Similar drugs are used to treat other viral infections such as HIV and hepatitis C, both alone and in combination with other antivirals.

Pfizer scientists hit an early stumbling block. Lab tests showed the drug candidate to be active against the new coronavirus, known as SARS-CoV-2, but the concentrations were not strong enough to fight the virus in humans, Allerton said.

Pfizer continued to work with the active component of this compound to formulate a drug that could be administered intravenously. But antivirals are more helpful if you catch illness early, “and it’s not easy with IV medication,” Allerton said.

In March 2020, scientists at Pfizer also began designing a new compound that could be absorbed through the stomach and taken as a pill, which they finalized in July, according to Allerton.

The discovery of a protease inhibitor that could be administered orally was “a bit of a masterpiece of chemistry,” said Mikael Dolsten, chief scientific officer of Pfizer.

Antivirals are more complex to develop than vaccines because they must target the virus after it has already replicated inside human cells, without damaging healthy cells. COVID-19 vaccines typically teach the human immune system to recognize and attack part of the “spike” protein that is specific for the coronavirus.

A COVID pill would likely only be taken for a few days, but drugmakers had to act slowly to keep it safe.

TRICKY TRIALS

The Merck and Roche drug candidates use mechanisms different from and between Pfizer’s to disrupt the virus replication machinery. But companies share similar testing challenges.

The first is to make sure that a patient receives the drug soon after infection with COVID-19. “It’s about treating as early as possible in the disease process, when the virus is growing,” said Dolsten of Pfizer.

And with high vaccination rates in some areas, trials need to be located in countries where COVID-19 is still on the rise.

In March of this year, Pfizer began early-stage clinical trials in the United States of its investigational oral treatment for COVID-19, known as PF-07321332. It followed a separate company trial of the intravenous drug that began last fall.

Dolsten declined to comment on how late-stage pending trials of either drug will be structured.

Merck’s antiviral drug candidate, called molnupiravir, recently suffered a setback. The company said last month that it would not continue its use in hospital patients. But Merck said it was transferring the drug to advanced stage trials on a select group of outpatients – especially those who had symptoms for no more than five days and with at least one risk factor for serious illness, such as advanced age. , obesity or diabetes.

Merck said it could have final data by September or October.

Roche and its partner Atea are also limiting participation in their recent late-stage trial of their drug AT-527 to patients with COVID-19 who have symptoms for less than five days. Atea said final test results are expected before the end of this year.

Our Standards: Thomson Reuters Trust Principles.

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