Covid antivirals lose spark as regulatory scrutiny increases

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Regulators have taken notice after a study sparked fresh doubts over the usefulness of a Covid drug made by US pharma group Merck, raising questions about the costly procurement of antivirals during the peak of the pandemic.

The Medicines and Healthcare products Regulatory Agency, the UK drugs watchdog, is assessing whether conditional marketing authorisation should be renewed for Merck’s molnupiravir, also known by the trade name Lagevrio.

“We continue to seek advice from the independent scientific advisory body, the Commission on Human Medicines,” it told the Financial Times. “Patient safety is our top priority and we are closely assessing the data to ensure that the benefits of Lagevrio outweigh the risks.”

The regulatory scrutiny increases focus on the safety and effectiveness of antivirals, such as Merck’s molnupiravir and Pfizer’s Paxlovid, that were marketed as drugs to treat Covid-19. A study in Nature last month linked molnupiravir to mutations that can transmit when the coronavirus spreads between patients.

“There is no evidence from randomised trials that either molnupiravir or Paxlovid will [still] be effective, now that most people have been either vaccinated or infected,” said Andy Hill, a senior visiting research fellow at Liverpool university’s pharmacology and therapeutics department.

Molnupiravir’s original UK approval in November 2021 was a global first. The MHRA, which said such annual authorisations were under “constant review”, declined to comment on when the review would be concluded.

The European Medicines Agency denied approval for molnupiravir after concerns about its efficacy, as first reported by the FT in 2022. Merck dropped an appeal after the regulator stressed its “view that the data submitted are not sufficient to satisfy EU regulatory requirements”. A person familiar with the process said Merck “understood there was no hope . . . [Lagevrio] is a bit burnt”.

The US Food and Drug Administration in late 2021 gave a severely restricted emergency approval, making it a treatment available to those for whom other drugs were not recommended.

Merck said talks with regulators on reviews of filings were ongoing. “We are evaluating our options on how we can generate additional evidence supportive of Lagevrio for the treatment of Covid-19.”

The Cypriot government allowed stocks to be used to treat cats suffering with another coronavirus in the Mediterranean country, though the company said it was not approved for veterinary treatment and no such studies were planned.

Whatever the outcome of the round of regulatory reviews, Merck has cashed in on demand for the drug. Its sales of more than $6bn since 2021 do not include royalties for cheaper versions of the drug. In the second quarter of 2023, sales plunged 83 per cent to $203mn compared with the year-ago period, which Merck said was due, also, to the UK not renewing orders.

Sales for Paxlovid, another oral antiviral which was in huge demand from China’s elites during a surge of cases in the country late last year, have also tanked, falling 98 per cent in the second quarter compared with the year-ago period. Yet Pfizer’s $19bn in Paxlovid sales were almost a fifth of its 2022 total.

If offshoots of Omicron, the current dominant strain, continue to display lower virulence and public immunity levels remain strong, there could be minimal demand for both drugs when they are no longer procured by the US government and become commercially available.

Hill said “these drugs could be causing overall harm”, citing a risk of birth defects if molnupiravir is given to “men or women of reproductive potential who do not use contraception” and a risk of fatal interactions in Paxlovid “if given with the wrong medication”.

He said clinical trials for both drugs included unvaccinated patients infected with more severe variants before Omicron’s surge, but “in 2023, the vast majority of people have been either vaccinated or infected at least once”. 

“Merck and Pfizer did not conduct new clinical trials to check that their drugs were still effective,” he said, with original trials only showing “marginal benefits”.

The official familiar with the EMA’s molnupiravir assessment agrees on their limited usability: “Antivirals did badly [during the pandemic] but Paxlovid showed they can be effective if used quickly.”