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As Merck and Pfizer prepare to release clinical trial results for investigational COVID-19 antiviral pills, competitors are aligning themselves with what they hope will be more powerful and convenient oral treatments.

Enanta Pharmaceuticals, Pardes Biosciences, Japanese Shionogi and Novartis said they have designed antivirals that specifically target the coronavirus while aiming to avoid potential shortcomings such as the need for multiple pills per day or known safety concerns.

Infectious disease experts have stressed that preventing COVID-19 through the wide use of vaccines remains the best way to control the pandemic. But they said the disease is here to stay and more practical treatments are needed.

“We must have oral alternatives for the removal of this virus. We have people who are not vaccinated who get sick, people whose vaccine protection decreases and people who cannot get vaccinated, ”said Dr. Robert Schooley, professor of infectious diseases at the Faculty of Medicine of the United States of America. ‘UC San Diego.

Pfizer and Merck, along with their partners Atea Pharmaceuticals and Roche AG have all said they may seek emergency approval for their COVID-19 antiviral pills this year.

The rivals are at least a year behind. Pardes started an early stage trial last month, Shionogi plans to start large-scale clinical trials by the end of the year, Enanta aims to start human trials early next year and Novartis still tests its pill on animals.

Enanta chief executive Jay Luly said reusing drugs originally developed for other viral infections was not an unreasonable approach. But it’s unclear how powerful they will be against COVID-19, or how well they can target lung tissue, where the virus takes hold.

The risk is that “if it isn’t a great effort … you will end up wasting time,” Luly said.

Antivirals are complex to develop because they must target the virus after it has already replicated inside human cells without damaging healthy cells. They should also be given early to be more effective.

Currently, intravenous and injected antibodies are the only treatments approved for outpatient COVID-19 patients.

Effective and convenient COVID-19 treatment could reach annual sales of over $ 10 billion, according to a recent estimate from Jefferies & Co. Merck has a contract with the US government that involves a price tag of $ 700 for treatment with its antiviral molnupiravir.

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Several classes of antiviral drugs are under study. Polymerase inhibitors such as Atea’s drug – first developed for hepatitis C – aim to disrupt the ability of the coronavirus to reproduce. There are also protease inhibitors, like the Pfizer pill, which are designed to block an enzyme that the virus needs to multiply earlier in its life cycle.

We are trying to stop the processes “that allow the virus to set up a replication factory,” said Uri Lopatin, CEO of Pardes, who is also developing a COVID-19 protease inhibitor.

Merck’s molnupiravir, developed with Ridgeback Therapeutics, was at one point envisioned as an influenza drug and works by introducing errors into the genetic code of the virus.

“The broad-spectrum activity of molnupiravir against RNA viruses, including other respiratory viruses, suggests that it should be a long-lasting and useful molecule,” said Jay Grobler, who oversees infectious diseases. and vaccines at Merck.

Merck said data shows the drug is unable to induce genetic changes in human cells, but men participating in its trials must refrain from heterosexual intercourse or agree to use contraception.

Until the results of the reproductive toxicology study are available, “we don’t know if there is a potential effect of the drug on semen,” said Nicholas Kartsonis, research director at Merck.

Both molnupiravir and the Pfizer pill are taken every 12 hours for five days. Pfizer’s medicine must be combined with an older antiviral ritonavir, which stimulates the activity of protease inhibitors but may cause gastrointestinal side effects and interfere with other medicines.

“It’s a nuisance to add a drug that you don’t need for a drug you want to take to be effective,” Schooley said.

Pfizer said that a low dose of ritonavir would help its protease inhibitor stay in the body longer and at higher concentrations.

Enanta, which derives most of its revenue from a hepatitis C deal with AbbVie Inc, scanned its library of antiviral compounds in early 2020. Instead, it chose to design a new protease inhibitor that targets a vital enzyme. for the ability of the coronavirus, and its variants, to reproduce.

The drug will be tested once a day with no increase in ritonavir, Luly said.

Lopatin said Pardes is reviewing the dosage once and twice a day and whether his medicine should be combined with ritonavir. “We don’t anticipate needing to use a booster,” he said.

Pardes received funding from Gilead Sciences, which waived an inhaled version of its remdesivir, an intravenous polymerase inhibitor approved for COVID-19 hospital patients.

Gilead is still working on an oral remdesivir, which was also first developed for hepatitis C and is currently the only antiviral approved for the treatment of COVID-19.