Merck scrambles as Molnuiravir fails PANORAMIC trial

The only question remaining is how long until the drug's authorization is pulled?

One of the most fascinating aspects of this pandemic is the high demand for snake oil, so long as its fresh. The alarmists seem to love the novelty of the previous two years, not just the novelty of the virus, but also the novelty of the “cures”.

The attack on ivermectin was one example where any attempt to examine old medicine was met with, not just resistance, but ridicule. Ironically, the ridicule has some advantages for ivermectin. The drug is one of the few that probably does not suffer from survivorship bias, or, at least, if it does suffer from survivorship bias, the bias is directed in the opposite way. I’ve mentioned the file-drawer effect where researchers are much more likely to publish positive results and throw away negative results. If anything, with ivermectin, researchers are more likely to throw away positive results and publish negative results to conform with expectations from the scientific community.

We see survivorship bias come into play prominently with Molnupiravir, A recent analysis of twelve studies out of India on the drug found scant details on the results. They found just one suspicious positive result, two seemingly negative results, and nine unknown results, which suggests either p-hacking by researchers to get a positive result, negative results being filed away, or both.

This isn’t surprising considering the initial trial of the drug was poorly randomized leading to positive interim results when most of the recipients had poor health and negative results in the second half of the trial when randomization improved.

One pill makes you larger and one pill makes you small. The ones that the Food and Drug Administration give us don't do anything at all.

I noted the randomization when the trial was released, and while I have not seen many in the scientific community actually pick up on the true cause for the positive interim result, many did, for their part, admit that the evidence for efficacy was weak.

Yet Molnupiravir has its fans. If you go back and read comments on the drug, especially shortly after it was authorized, people were complaining that us backwater skeptics “still won’t trust The Science”. Why? Because, like the virus, Molnupiravir is new and shiny. These people think that for the first time in history, we have mastered the science. And none have mastered it more so than the regulators who are approving shiny new drugs like Molnupiravir.

Luckily, there is no need to worry about negative trial results being withheld for Molnupiravir any longer. It’s been a long time coming, but we finally have results from the much anticipated PANORAMIC trial, a massive randomized control of Merck’s antiviral drug Molnupiravir.

And they aren’t positive.

As we long suspected, the results showed that Merck’s antiviral does not reduce the risk of hospitalization or death. The final results of the PANORAMIC trial have already been scrubbed from SSRN, but we can still see from an archived copy of the abstract that there isn’t much to celebrate for Merck. Of those that received the drug, 103 were either hospitalized or died versus 96 from the control group.

For their part, the drug giant had a press release admitting as much. They decided to focus on the fact that the time to first recovery was lower in the Molnupiravir cohort. That result, of course, tells us very little considering Molnupiravir is similar to Paxlovid in that it is associated with rebound infections. Covering up the symptoms of an infection, rather than fighting the infection, only provides a vector for further community spread of the virus.

Rebounds not unique to Paxlovid?

Of course, Merck tried to shoehorn the results of a weak observational study into the press release, which is comical considering the survivorship bias problem inherent with the drug. More troubling for the company is the amount of researchers who have been calling for re-evaluating Molnupiravir’s authorization once the PANORAMIC trial results have been released. Investors beware.