Wow! I had no idea my blog was influencing the FDA! Within hours of my last blog, the FDA authorized both new oral antiviral drugs, Pfizer’s Paxlovid and Merck’s Molnupiravir. That’s just what I called for in my last post, Covid Therapeutics Taking a Back Seat. Seriously, I’m sure my blog had nothing to do with it; but it’s nice to see the government finally coming around to thinking like many physicians like myself. It’s great to push vaccines, which are very important, but therapeutic innovations like these two new oral treatments for Covid can be equally impressive in helping us return to some sense of normalcy.
But the news is not all good. Since the FDA was so slow to approve these drugs, and the Biden Administration was slow to appreciate their importance, these pharmaceutical advances in therapeutics will be in short supply this winter. The Emergency Use Authorization (EUA) of the FDA is actually only for adults at high risk of severe illness. Both drugs will be available by prescription only with proof of a positive Covid test and should be taken within five days of symptom onset.
How do these drugs work? Both drugs interfere with virus replication, though by different means. Virus replication is the process of making more virus that leads to overwhelming the host. When drugs interfere with this process, they prevent the virus from spreading and the host immune system overwhelms the virus. Molnupiravir was found to reduce hospitalizations by about 30% and deaths by nearly 90%. Early results from its trial showed a 50% reduction in hospitalization, though efficacy declined later for unclear reasons. Paxlovid reduced hospitalization by about 90%.
Expect rationing of the drugs this winter. The Biden Administration ordered 10 million packs of Paxlovid in mid-November after strong preliminary trial results. But other countries have put in large orders, and Pfizer says it expects to manufacture 180,000 courses by the end of this year. Pfizer has licensed the drug to the Medicines Patent Pool to ramp up supply in lower-income countries, but production can take six to eight months. Advance government orders, like Operation Warp Speed for vaccines, might have accelerated production, says The Wall Street Journal.
The Biden Administration has ordered a mere 3.1 million treatment courses of Molnupiravir. The U.K. has purchased 2.2 million courses for its 68 million citizens. Most U.S. courses will be available by the end of January, but the FDA says the drug should only be used when other authorized treatments aren’t accessible or clinically appropriate. That means doctors are less likely to prescribe it.
The Wall Street Journal editorial board says, “Vaccines appear to have reduced the Biden Administration’s urgency to approve and accelerate new treatments, especially antivirals. Officials failed to foresee how vaccine efficacy would wane over time and demand would plateau. They can’t be faulted for that. But they could have hedged by fast-tracking oral treatments, as Operation Warp Speed did, by investing in multiple vaccine makers using different technology.”
The National Institutes of Health (NIH) also bears some of the blame. They bet heavily on monoclonal antibodies, which have been enormously helpful. But it overlooked the importance of other drugs for early treatment to prevent infected individuals from getting sicker. Early treatment therapeutics are the key to reducing hospitalizations. NIH was also late to fund a large trial on repurposing existing drugs such as the anti-parasitic ivermectin, anti-depressant fluvoxamine and asthma inhaling fluticasone. These drugs all show promising antiviral effects, but final results aren’t in yet.
We should celebrate the approval of these two new oral drugs to treat Covid, but it’s hard not to wonder how many more lives would have been saved if they had been approved earlier. WSJ says, “Vaccines have saved hundreds of thousands of lives, but many more would be saved if oral treatments like Paxlovid and Molnupiravir were available sooner. The drugs represent a huge pharmaceutical success but a missed government opportunity.”