US backs another Covid-19 booster

But a potentially more interesting advisory committee, for Merck and Ridgeback’s molnupiravir, awaits.

FDA endorsement of a booster of Moderna’s Covid-19 vaccine looks likely to emerge in the coming days after the unanimous backing by an advisory committee last night. And today the panel of experts will consider another regimen: Johnson & Johnson’s application for patients to receive a second shot of its supposedly once-and-done product.

This too will probably be endorsed, given concerns about all Covid-19 vaccines’ waning effectiveness. This is compounded with the J&J product, Ad26.COV2.S, because the protection bestowed by the first shot was already lower than that seen with mRNA-based vaccines. Notably, panellists will also be asked their opinion on early data on mixing different vaccine types.

Today’s panel will also be shown a short presentation of results from the NIH Mix and Match booster study, which concluded that people who got Ad26.COV2.S got a better “boost” from an mRNA jab. According to reports US recipients of Ad26.COV2.S are already being offered boosters with Pfizer/Biontech's Comirnaty, something that could happen more if positive comments emerge later today.

The dominance of the Pfizer jab is already reflected in sellside analyst forecasts for the four main Covid-19 vaccines. If the numbers do move, this will likely be further in Comirnaty’s favour; having already received the FDA’s backing for a booster shot, the Pfizer vaccine continues to enjoy first-mover advantage.

Another advisory committee on the horizon offers more potential to change the landscape, albeit concerning Covid-19 treatments, which for now means monoclonal antibodies. The FDA yesterday said it would convene its experts on November 30 to discuss an emergency use authorisation for Merck & Co and Ridgeback’s molnupiravir.

The oral antiviral smashed expectations with a 50% reduction in the risk of hospitalisation or death in the Move-Out trial earlier this month, and Merck wasted no time submitting the data to the US regulator.

The convenience advantages of such a product versus infused antibodies is clear, although molnupiravir is thought unlikely to match the MAbs' efficacy in all settings. And of course the project must first clear regulatory muster.

Toxicity could give the agency pause, particularly around potential mutagenicity. Molnupiravir works by causing a large number of genetic mutations in the replicating virus. Some scientists are concerned that the agent might also cause mutations in the RNA of patients who take it.

Merck insists that it has looked very closely at this issue and found nothing worrisome, and the financial community seems to agree. Analysts at Evercore ISI made an interesting point: other antivirals, including Pfizer’s PF-07321332, do not have a mutagenic mechanism, and this could provide differentiation if the FDA insists on label warnings.

Vaccinated excluded

Another live issue for molnupiravir is the population in which any EUA might be granted, given that Merck excluded vaccinated patients in its trials. It must be hoped of course that in the real world very few vaccinated patients will have to be considered for molnupiravir.

But whether vaccinated people should receive the antiviral at all is likely to be a subject of debate. Proving a benefit would be very hard, as it would be almost impossible to power a clinical trial for hospitalisations or deaths in these patients.

The argument is perhaps commercial anyway. As Bernstein analysts put it, if Merck maintains a $700 price, its use would be unjustifiable in the already vaccinated. They believe that if the cost remains at that level payers would restrict molnupiravir to high-risk unvaccinated individuals or the immunocompromised, in much the same way that the antibodies will probably be used.

As such, whether Merck pursues a high-price/low-volume or low-price/high-volume strategy is a major unknown, at least for those trying to put a number on this opportunity. Data on other antivirals could also change the picture – important readouts from Pfizer and Roche/Atea are expected before year end.

Whether molnupiravir works in milder patients, and thus might be used in the larger, lower-risk population, is another swing factor.

As such, many sellside analysts are waiting for these pieces of the picture to fall into place before publishing sales forecasts. The chart below is constructed from the three sets of numbers that Evaluate Vantage managed to find.

But it is clear that the oral antiviral opportunity could be considerably larger – and have considerably longer legs – than that for the MAbs. As with most Covid-19-related situations, this picture could soon change once again. 

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