Replies to post #41524 on Biotech Values

[dewophile]

i don't know. i see your point but then again these combos will eventually be done, and a rare idiosyncratic reaction could always happen at any time which will weigh heavily on commercial potential, whether pre or post-approval..granted if it is going to pop up you'd rather have the drug already approved and then black box it (but if serious enough to halt a trial might be serious enough to pull from market)...but i also think you have to keep in mind there is tremendous experience using protease-polymerase combos (albeit in a different indication - HIV, and not in combo with immunomodulators), but still there is a track record here that probably lowers risk, and if safety profiles, metabolic pathways, and complementary MOAs exist I think the risk is rather minute (at least for some serious deal-breaker type side effect)..and if it represents the best way forward for probably the most significant subset of the HCV market in terms of unmet need (which will weigh favorably with the FDA) I wouldn't be surprised to see it happen despite the very valid concerns and arguments you raise

[gofishmarko]

>> If the FDA saw a serious—perhaps life-threatening—problem in a combination trial, they could place a clinical hold on all VX-950 development until they sorted it out. Is this a risk VRTX will be willing to take? <<

Given the longstanding unmet need for an effective treatment for nonresponders , I would expect the FDA to be relatively accomodating in this situation. I can imagine a conversation where the FDA agrees that any new , unexpected SAEs in the combo trial will be assumed to be due to the combo and not to VX950 , assuming a good monotherapy database , of course , and subject to change based on postmarketing safety data. Absent this sort of up-front understanding , however , I agree that VRTX would be wise to wait on the combo trials.

BTW , Alam's CC answer to Werber's ITT question sounded like the ramblings of a madman. I bet Alam's eyes were spinning in circles. No wonder he wanted to take it offline.

The VRTX halo is showing some corrosion.

[Jonathan Robinson]

If the FDA saw a serious—perhaps life-threatening—problem in a combination trial, they could place a clinical hold on all VX-950 development until they sorted it out. Is this a risk VRTX will be willing to take?


I assume this is called the Elan Scenario.

Jon

[gofishmarko]

Re : HCV combo trials

After listening today to the NIH workshop on cancer vaccines / immunotherapy , I'm inclined to agree with Dew that combo studies in HCV won't happen until the individual drugs are approved , if then. The questions to the panel today largely focused on this same issue , i.e. cancer trials using combos of unapproved drugs , and the FDA reps dodged and weaved ( "You CMA , I'll CYA ." ) , leaving the question unanswered , and the problem unsolved. If the reluctance exists among sponsors to do these studies for cancer , where the tolerance for SAEs is much higher , then surely it exists in spades for an indication like HCV.

The FDA could largely solve this problem by simply announcing with conviction that combo studies done post-approval ( of the relevant monotherapy drugs ) will be just as likely - or unlikely - to result in withdrawal of the original approval(s) as they are to result in a failure to approve in the first place , so sponsors may as well get busy with the combo registration studies concurrently with their monotherapy registration studies.

The FDA will never do this of course , because pulling drugs from the market post-approval makes it look like they missed something during the approval process. This also explains their long-standing reluctance to enforce collection and reporting of post-marketing safety data.

All-in-all , my respect for the FDA took a dive today. We need a do-over on the entire drug approval process , IMO.