Replies to post #184500 on Biotech Values

[biomaven0]

Basically the rate per length of exposure has stayed pretty constant. Given that atherosclerosis is a cumulative process, there is an argument that it could have gotten worse over time.

Basically I think pona is pretty much dead as a first or second line agent, but it is very much alive as a third line agent.

This recent paper (going with one of the ASH presentations) makes this point:

Leuk Res. 2014 Nov 1. pii: S0145-2126(14)00327-0. doi: 10.1016/j.leukres.2014.10.005. [Epub ahead of print]
Comparative efficacy of tyrosine kinase inhibitor treatments in the third-line setting, for chronic-phase chronic myelogenous leukemia after failure of second-generation tyrosine kinase inhibitors.
Lipton JH1, Bryden P2, Sidhu MK3, Huang H4, McGarry LJ4, Lustgarten S4, Mealing S2, Woods B2, Whelan J2, Hawkins N2.
Author information
Abstract
We compared the efficacy of ponatinib and second-generation tyrosine kinase inhibitors (2G-TKIs: bosutinib, dasatinib, and nilotinib) in chronic phase CML resistant/intolerant to =1 prior 2G-TKI. Estimated probabilities of CCyR with 2G-TKI ranged from 22% to 26%, compared with 60% (95% CrI 52-68%) with ponatinib. The estimated probability of ponatinib providing higher response rate than all other included treatments was 99% (CCyR) and 97% (MCyR). Use of further 2G-TKI may provide limited benefit in CP-CML patients resistant/intolerant to prior 2G-TKI treatment. Compared with 2G-TKIs, ponatinib is estimated to provide substantially higher probability of achieving CCyR and MCyR; safety was not compared.

[jq1234]

Yes, but you would hope the rate would decelerate rather than accelerate after significant dose reduction. At 30-month, CP-CML ATE SAE rate was 9.2 per 100 patient exposure years, at 38-month it is 10.4 per 100 patient exposure years - this is the metric the company liked to use.

In addition, you can look at phase 1 data with 48-month follow-up today, ATE SAE rate for CP-CML is 30%, ATE AE rate is 40% - can't compare to FDA number because FDA used all patients while ARIA presented only CP-CML- remember more than 1/3 of CP-CML patients in this trial started Iclusig at 30mg or lower, and then dose reduction at some point as well. You can pretty much draw inference from lower starting doses. I essentially agree with Peter, Iclusig efficacy is there even with lower dose, but ATE SAE rate will not drop much if any over time.