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Within the race for a COVID-19 therapy pill

© Reuters. An experimental COVID-19 treatment pill called molnupiravir, developed by Merck & Co Inc and Ridgeback Biotherapeutics LP, can be seen in this undated flyer photo released by Merck & Co Inc and received by Reuters on May 17, 2021. Merck & Co Inc / Hand

By Deena Beasley

LOS ANGELES (Reuters) – In early 2020, when a new deadly coronavirus spread around the world, Pfizer Inc (NYSE 🙂 has assembled a so-called "SWAT team" of scientists and chemists to determine a possible treatment to combat COVID-19.

The US pharmaceutical company, which had begun research into a vaccine, also wanted to make a pill that could prevent the infection from progressing, much like the popular drug Tamiflu used to fight influenza. The team searched Pfizer's molecular library for unused compounds to speed up the process and quickly identified a promising candidate.

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

Pfizer and its competitors, including US-based Merck & Co Inc and Swiss pharmaceutical company Roche Holding AG (OTC :), are striving to create the first antiviral pill that people can take at the early signs of the disease. Their common goal: to fill an important treatment hole by helping people recently infected with coronavirus avoid getting seriously ill and being hospitalized.

But after nearly 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 German partner BioNTech SE (NASDAQ :), which was first approved for use in the United States in December.

Pfizer's experience underscores 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 needs to prevent a virus from spreading in the body while being selective enough to avoid harming healthy cells.

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

Albert Bourla, chief executive of Pfizer, said the company could apply for an emergency approval for a COVID-19 pill in the US as early as the end of this year.

"At the moment we have very good reasons to believe that we can be successful," said Bourla via videoconference at an economic forum in Greece last week.

Pfizer and its competitors say the development process was much faster than the years it would normally take to create a drug that can be taken as a pill.

Merck and Roche recently started late-stage human studies and also said their drugs could be ready by the end of this year. Merck is developing its drug in partnership with Biotech Ridgeback Biotherapeutics LP and Roche is working with Atea Pharmaceuticals Inc.

Governments around the world have spent billions of dollars developing vaccines, but Pfizer, Merck, and Roche say they did not receive government funding to develop oral antivirals for the disease.

"HUNT FOR THE NEXT TAMIFLU"

While the rate of new COVID-19 infections is currently falling in some countries, others continue to grapple with 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 continue to hesitate to take vaccines.

Scientists predict that COVID-19 – which has killed more than 3.5 million people worldwide – could become a seasonal illness similar to influenza.

"We need a pill that will keep people out of the hospital," said Dr. Rajesh Gandhi, professor and specialist in infectious diseases at Harvard Medical School.

Doctors have tried a number of existing oral drugs in the fight against COVID-19, but none of them have yet managed to conduct rigorous clinical tests.

Currently, the only treatments that help COVID-19 patients avoid hospital stays are antibody drugs, which require long intravenous infusions and are less effective against variants of the coronavirus.

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

For patients who have already been hospitalized with COVID-19, treatment often includes steroids or anti-inflammatory drugs to relieve symptoms of the infection. However, these drugs do not target the virus itself. The only antiviral drug approved in the US for the treatment of COVID-19 is Remdesivir from Gilead Sciences (NASDAQ 🙂 Inc, which is administered intravenously and used only for hospital patients.

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

"We're all looking for the next Tamiflu," said Merdad Parsey, Gilead's chief medical officer.

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.

‘CHEMISTRY MASTERPIECE’

Pfizer scientists and chemists began the search for an antiviral treatment in January last year. They quickly focused on a connection dating back to 2003 when the company was seeking treatment for the first global SARS pandemic, said Charlotte Allerton, Pfizer's director of drug design.

The compound belongs to a class known as protease inhibitors, which is designed to block a key enzyme or protease that is essential for the coronavirus to be able to reproduce. Similar drugs are used to treat other viral infections, such as HIV and hepatitis C, both alone and in combination with other antiviral agents.

Pfizer's scientists encountered an early stumbling block. Laboratory tests (NYSE 🙂 showed the drug candidate was active against the novel coronavirus known as SARS-CoV-2, but concentrations weren't 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. However, antivirals are most useful when you get sick early on with a disease. "And that's not easy with an IV drug," said Allerton.

In March 2020, Pfizer scientists also began developing a new compound that can be absorbed through the stomach and taken as a pill. According to Allerton, they finished this in July.

The discovery of a protease inhibitor that can be administered orally is "a masterpiece of chemistry," said Mikael Dolsten, Pfizer's chief scientific officer.

Antiviral drugs are more complex to develop than vaccines because they have to target the virus after it has already replicated in human cells without harming healthy cells. COVID-19 vaccines typically teach the human immune system to recognize and attack a portion of the coronavirus-specific "spike" protein.

A COVID pill would likely only be taken for a few days, but drug manufacturers had to move slowly to ensure safety.

TRICKY TRIALS

The drug candidates from Merck and Roche use different mechanisms with Pfizer and with each other to disrupt the replication machinery of the virus. However, companies share similar testing challenges.

One is to make sure a patient receives the drug soon after being infected with COVID-19. "It's about treating as early as possible in the disease process if the virus spreads," said Dolsten from Pfizer.

And with vaccination rates high in some regions, studies need to be done in countries where COVID-19 is still on the rise.

In March of this year, Pfizer began early human studies in the United States with its experimental oral COVID-19 treatment known as PF-07321332. This was followed by a separate study by the company with the intravenous drug, which began last fall.

Dolsten declined to comment on how the upcoming studies on both late-stage drugs will be structured.

Merck's antiviral drug candidate called molnupiravir recently had a setback. The company said last month it would not continue its use in hospital patients. However, Merck said the drug is being used in late-stage studies with a narrow group of patients who have not been hospitalized – especially those who have had symptoms for no more than five days and who have at least one risk factor for serious illness such as advanced age , Obesity or diabetes.

Merck said final data could be in by September or October.

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

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