Replies to post #257107 on Biotech Values

[iwfal]

OCUL

There's are lots of studies backing up the 40% discontinuation rate for anti-VEGF therapy that Dugel cites all the time. Easy enough to find.

Sure, but there is a good method to avoid that - see **protocol** in Eylea 8 mg or, better yet, Vabysmo (a surprisingly large fraction of patients can make it out to 20 weeks or more). At this point it is probably substantially more than 50% of doctors who do this well, and this improvement is recent. So the rates of 40% discontinuation in a year are almost certainly substantially outdated. (Note: ideally SOL-1 would have been in patients who were treatment resistant (ie Vabysmo failures that require 8 week treatment spacing. Another way to say this is... 'how much better would Axitinib have been vs Vabysmo?' My guess is not much and comes with additional aggregate AE.)

Note: Vabysmo, the drug, probably isn't that much better as a drug than Eylea 8mg. Much of the secret sauce of Vabysmo was in the trial protocol - and now in treatment protocol in most local doctors' offices.

The cataract rate was higher at 7% but Ocular claims they weren't caused by treatment and in any event, the 7% rate is equal to that shown in the Eylea package insert,

Cataract rate gets the attention, but would not be my primary concern as a patient since a very large fraction of people end up having to get cataract surgery anyway. It's relatively quick and easy. But I am dubious that the fairly large imbalance in aggregate AE across AE types goes away and it is most probably drug related (and this is a very large, continuous, dose of drug much broader than mab). What is less clear is how much is additive across doses.

Note: I suspect the case for Axitinib in NPDR is quite different - the VEGF mab specific MOA appears a lot less useful in NPDR (Eylea MOA is arguably largely about drying out - interesting note: the patients who failed Eylea in SOL-1 seemed to be concentrated in those who had not really consolidated into a dried out state), and the treatment burden for Eylea seems not worthwhile. But exactly how this plays out will depend on repeat dosing AE in the larger SOL-R trial.

Comment: IIRC a previous wAMD drug which submitted for approval ended up getting approved for a single dose. No continued dosing because continued dosing had unacceptable side effects. Would be interesting to see if the FDA accepts SOL-1 submission and makes repeat dosing wait until SOL-R.

Comment 2: the data they presented in the PR was very clearly cherry picked in the sense that some was 'responders only' and some was ITT. This seems unlikely to be fully justified. And it makes it hard to understand real BCVA etc.