Replies to post #178603 on Biotech Values

[DewDiligence]

Re: ARIA’s EPIC post-mortem

In today’s PR, the safety comparison of Iclusig relative to Gleevec was as bad as the efficacy comparison (which you posted) was good (http://investor.ariad.com/phoenix.zhtml?c=118422&p=irol-newsArticle&ID=1936051&highlight ):

• More ponatinib patients experienced vascular occlusive events (8%, n=12) vs. imatinib patients (2%, n=3).

• There was a higher incidence of treatment-emergent grade 3 or 4 AEs for ponatinib vs. imatinib. The most common AEs were lipase increase (14%, n=22) vs. (2%, n=3), thrombocytopenia (12%, n=19) vs. (7%, n=10), rash (7%, n=10) vs. (1%, n=2).

• There also was a higher incidence of serious AEs for ponatinib vs. imatinib. The most common SAE was pancreatitis (3%, n=5) on the ponatinib arm; none reported with imatinib.

Of course, the high starting dose was partly to blame for these safety results.

CC Monday at 8:30am ET.

[jq1234]

>> If it wasn't for the toxicity, Ariad would redefine the space, imo.

That's like saying nothing in drug development. If it weren't for toxicity, many more drugs with great efficacy would have been on the market.

Per EPIC ASCO poster disclosure:

Prespecified DMC assessment: Mandatory risk/benefit analysis will be implemented at the time when a statistically significant difference (P value <0.05) in serious grade 3/4 ischemic adverse events between both arms or =5 (and P value <0.2) fatal myocardial infarctions and/or other fatal ischemic events occur

– At the time of termination, this threshold had not been crossed: serious grade 3/4 ischemic events in ponatinib vs imatinib arm were 5 and 1, respectively, P=0.2142

- Data as of Apr 1, 2014 are presented; median (range) follow-up was 5.1 (0.03-17.6) months: Arterial thrombotic events SAEs: ponatinib vs imatinib arm were 10 and 1, respectively.

Consider EPIC trial had very short follow-up, given the number above at termination and further follow-up, thus even if FDA hadn't taken action against Iclusig last year, EPIC trial could still be stopped due to safety issue by DMC before planned interim efficacy analysis originally planned for later this year if trial had continued.

http://investor.ariad.com/phoenix.zhtml?c=118422&p=InvestorDownloads

By the way, I have to give ARIA credit for much thorough in data presentation from clinical trials since ASH last year than before. This is something every drug company especially small biotech should do but somehow don't. Without, it is very difficult to assess a drug's overall risk/benefit accurately.

[JJM760]

"If not for the toxicity" is like saying if not for a few inches I'd be a pornstar.