COVID-19 pill developers aim to top Merck, Pfizer efforts
September 28, 2021; 2:33 PM EDT
Antivirals are complex to develop because they must target the virus after it is already replicating inside human cells without damaging healthy cells. They also need to be given early to be most effective.
Currently, intravenous and injected antibodies are the only approved treatments for non-hospitalized COVID-19 patients.
An effective, convenient COVID-19 treatment could reach annual sales of over $10 billion, according to a recent Jefferies & Co estimate. Merck has a contract with the U.S. government that implies a price of $700 for a course of treatment with its antiviral molnupiravir.
SEARCH FOR AN EASY TREATMENT
Several classes of antiviral drugs are being explored. Polymerase inhibitors such as Atea’s drug – first developed for hepatitis C – aim to disrupt the ability of the coronavirus to make copies of itself. There are also protease inhibitors, like Pfizer’s pill, which are designed to block an enzyme the virus needs in order to multiply earlier in its lifecycle.
We are trying to halt the processes “that allow the virus to set up a replication factory,” said Uri Lopatin, CEO at Pardes, which is also developing a COVID-19 protease inhibitor.
Merck’s molnupiravir, developed with Ridgeback Biotherapeutics, was at one point envisioned as a flu 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 durable, useful molecule,” said Jay Grobler, who oversees infectious disease and vaccines at Merck.
Merck said data shows the drug is not capable of inducing genetic changes in human cells, but men in its trials have to abstain from heterosexual intercourse or agree to use contraception.
Until reproductive toxicology study results are available, “we don’t know if there’s any potential effect of drug on sperm,” said Merck research executive Nicholas Kartsonis.
Both molnupiravir and Pfizer’s pill are taken every 12 hours for five days. Pfizer’s drug must be combined with older antiviral ritonavir, which boosts the activity of protease inhibitors but can cause gastrointestinal side effects and interfere with other medications.
“It is a nuisance to add a drug you don’t need to have a drug you want to take be effective,” Schooley said.
Pfizer said a low dose of ritonavir will help its protease inhibitor remain in the body longer and at higher concentrations.
Enanta, which gets most of its revenue from a hepatitis C deal with AbbVie Inc (ABBV.N), scanned its library of antiviral compounds early in 2020. It instead chose to design a new protease inhibitor that targets an enzyme vital to the ability of the coronavirus, and its variants, to replicate.
The drug will be tested at once daily dosing with no ritonavir boosting, Luly said.
Lopatin said Pardes is assessing once- and twice-a-day dosing and whether its drug needs to be combined with ritonavir. “We do not anticipate that we will need to use a booster,” he said.
Pardes received funding from Gilead Sciences (GILD.O), which gave up on an inhaled version of its remdesivir, an intravenous polymerase inhibitor approved for hospitalized COVID-19 patients.
Gilead is still working an oral remdesivir, which was also first developed for hepatitis C and is currently the only antiviral approved for treating COVID-19.
(This story corrects name to Ridgeback Biotherapeutics)
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