🚨💊HUGE news: @US_FDA has finally granted approval to @ShionogiUS’s Xocova (Ensitrelvir), a 2nd-generation antiviral targeting SARS-CoV-2. The approval is for the indication of “post-exposure prophylaxis of COVID-19 following contact with an individual who has COVID-19”. However, just like with any drug, it can obviously also be used off-label (e.g. treatment of both acute COVID or Long COVID). In Japan, Xocova received Emergency Use Authorization for the treatment of acute COVID all the way back in November 2022, received full approval in March 2024, and an expansion to include post-exposure prophylaxis in March 2026. The post-exposure prophylaxis indications are based on the SCORPIO-PEP trial (nejm.org/doi/full/10.1056/NE…), where Xocova reduced the incidence of COVID-19 after household exposure by 67%, from 9.0% down to 2.9%. Mechanically, Xocova is the same class of drug as Paxlovid - a 3C-like protease inhibitor that inhibits viral replication. From our best understanding, Xocova is probably slightly more potent than Paxlovid, but the more definitive advantage is that it comes with less side effects and less drug interactions (which are caused by the Ritonavir component of Paxlovid, added to boost the concentration of the actual antiviral, Nirmatrelvir). Xocova should be useful for lowering viral load during an acute infection, especially if taken within a couple or days of symptom onset, which may help shorten the duration of acute symptoms. Will it do anything to prevent long-term damage or the development of Long COVID? Almost certainly not, just like Paxlovid, but I’d be more inclined to tell people that it’s worth trying if we’re no longer dealing with the side effect profile of Paxlovid. Where it makes the most sense to use Xocova, just like with Paxlovid, is as a component of polytherapy for Long COVID driven by viral persistence. The big issue there, however, is that you need a longer course of these antivirals than most physicians are willing to prescribe and/or most insurance companies are willing to cover. And they’re generally not very effective as a monotherapy, you need to pair these oral antivirals with other therapies for better coverage and tissue penetration (eg. monoclonal antibodies and Nuvaxovid, and potentially even a 2nd antiviral like Remdesivir). All in all, this is a very important and long overdue approval. It’s not a game-changing silver bullet, and notably, nobody should really be expecting to use or rely on Xocova in a way that they wouldn’t be open to using or relying on Paxlovid in the present. But there are plenty of applications for it, and Xocova should absolutely be seen as another Swiss cheese layer / tool in the toolbox for COVID conscious community members and any allied medical providers.