Enanta Pharmaceuticals Inc (ENTA)

[vinmantoo]

Some more observations on why viral RNA levels in the nose aren't a good metric for anti-Covid efficacy. I also point to data from the Shionogi's drug trial isn't as impressive as they would like you to believe or some ENTA critics here assert.

The link to the Shionogi presentation (provided by dewophile). If you notice on slide 9 there is once again is NOT a dose dependent response as the 250mg dose is LESS effective in reducing viral titer than the 125mg dose. In fact, by day 6 the 250mg dose is no better than placebo.

https://www.shionogi.com/content/dam/shionogi/global/investors/ir-library/presentation/2022/ECCMID%20Ph2b%20presentation%20final2.pdf

The same is true for slide 12, total symptom change from baseline as the 250mg dose was LESS effective than the 125mg dose. Something weird is happening, and it sure doesn't inspire confidence.

In slide 14 the middle panel assesses systemic symptoms. It looks like the 250mg dose is essentially a placebo and the 125mg dose had at best a minor effect. Once again NOT a dose dependent response. The only one is a clear separation was respiratory symptoms but not digestive symptoms.

Some last thoughts about the disconnect between viral levels in nasal swabs. The first a general one that people often keep testing positive for RNA long after their symptoms are gone. The second is the issue of the faster viral clearance in the placebo arm in the ENTA study (see slide 22 of the ENTA presentation for SPRINT below). For placebos at day 3, the Shionogi phase 2b study showed maybe a 0.8 log decline but for SPRINT is was already 1.5 log decline. By day 5, the Shionogi phase 2b study showed a 2 log decline whereas the ENTA placebo had a 3.5 log decline. If the decline of viral RNA in the nasal swab correlates with symptom improvement, then the placebo group in the SPRINT study should have reduced their symptoms faster than in the Shionogi phase 2b study.

However, look at slide 17 of the ENTA presentation. The left side is ENTA's SPRINT data and the right side is Shionogi phase 2b study. By 3 days, total symptom score in Shionogi's placebo is down just over 4 log (~4.5 log) whereas in SPRINT, there is a bit less than a 4 log drop. By 4 days, total symptom score in Shionogi's placebo is down 6 logs as is in the SPRINT study. So it sure looks like the more rapid clearance in the SPRINT trial doesn't correlate with more rapid patient symptom improvement. This once again points to nasal swabs not being a good metric for drug efficacy.

https://ir.enanta.com/static-files/c9eca2f1-296c-4a0c-9ce4-d668229f1ec5