Thread by @YinPD

THREAD (1/X) It's interesting that favipiravir (Avigan), is getting relatively little press in U.S. and western countries compared to #hydroxychloroquine (HQ). #COVID19 pilot data at least as promising as any currently available HQ data presented thus far.

3/X Currently data supporting FPV (oral) comes from a Chinese open label pilot study.
It was NOT randomized, but patients were consecutively screened, which means they weren't cherry picked. Lopinavir/ritonavir (LPVr) was used as an active control
sciencedirect.com/science/articl…

4/X The LPVr arm was enrolled THE WEEK prior from consecutive screened pts. LPVr was not shown to have benefit in COVID19 pts with severe disease, a population excluded in this FPV trial nejm.org/doi/pdf/10.105…

5/X Nonetheless, LPVr is a reasonable "historic" control, having enrolled consecutively only 1 week prior, presumably with same eligibility criteria. Both the LPVr and FPV treatment arms received inhaled interferon, so this also has to be factored into results. Study was 2 wks

6/X Baseline characteristics of FPV (N=35) and LPVr (N=45) were comparable, including viral loads (VL) at screening (Cycle threshold (Ct) values ~30). CT scans were evaluated by blinded reader using prespecified scoring system.

7/X The median time to viral clearance for the FPV and LPVr arms were 4 days vs 11 days showing statistically significant benefit for FPV

8/X On D14 there's a statistical improvement in CT Scans for FPV compared to LPVr (91% vs 62%). Importantly there was time to viral clearance (< or > 7 days) correlated with degree of improvement seen on chest CT; suggests VL is reasonable surrogate for clinical improvement

9/X FPVr was well tolerated, and has a good safety database given its approval in Japan since 2014. I would like to see clinical outcomes for patients in this study (ie hospital discharge, ICU admission, death) which I suspect will be reported when available

10/X If manufacturing can be ramped up, this FPVr may offer a good option for treatment of mild/moderate COVID19 infections, if efficacy is confirmed in Ph3 studies. It will be up to FDA and EMA to provide the appropriate authorization for patients.

2/X Favipiravir (FPV) is not approved in many countries outside of Japan, although China recently approved it for COVID-19. New trials are being conducted in multiple countries including Italy (not in U.S. yet) europost.eu/en/a/view/ital…

11/X New #favipiravir (FPV) clinical data available as of 27March suggests benefit in moderate disease #COVID19 populations. However, there are important caveats that make interpretation of this study difficult
medrxiv.org/content/10.110…

12/X The study randomizes FPV (N=116) vs active comparator arbidol (N=120). I'm not familiar with arbidol, but it appears to have a MoA of inhibiting membrane fusion. Haven't seen any data related to SARS-CoV2 activity, but its being used in China and Russia

13/X Pts had <12 days of symptoms and diagnosed as "COVID-19 pneumonia". Treatment was 7-10 d. However, it's unclear to me how many of these patients had actual infection as only 38-47% had + PCR. They DID NOT analyze data based on patients with actual + PCR and pneumonia.

14/X The study did suggest a greater improvement in clinical recovery (predefined in protocol) for FPV vs arbidol (61 vs 51%, respectively), at Day 7, that was not statistically significant for the OVERALL population (primary outcome)

15/X Most pts had moderate disease (85-90%) while the rest had severe disease. Subset analysis suggests statistical improvement in pts with moderate disease (71% vs 56%) favoring FPV. However, multiple comparisons were not accounted for so this is only hypothesis generating

16/X Severe pt population was small so limited conclusions can be made. Key limitations of study include: not analyzing data based on pts actually diagnosis (PCR +) of COVID19, not having a treatment arm with no therapy (does arbidol have activity), and inadequate power.