Biotech Values

[gofishmarko]

>>>> IMHO we will likely see combos of oral HCV inhibitors planned this year. I suspect when both compounds are in PHIII, there is sufficient data to analyze the potential combo risk. Some of the potential candidates still have very good safety profiles. And given some of VRTX's recent results, I think they are now highly motivated to look at other non-approved drugs in a win-win-win (VRTX-partner-patient) type situation. <<<<

I hope you're right about this , but after listening to the FDA folks yesterday I'm inclined to agree with Dew that they will delay for fear of jeopardizing their ongoing
"monotherapy" registration trials.

Imagine these two hypothetical scenarios for an examination of a VX950 / NM283 combo. Let's say VRTX and IDIX are both well into their P3 registration trials , they both have seen excellent safety and efficacy in the monotherapy trials , and both expect to get approval and capture significant market share. However , both also recognize that a combo of VX950 plus NM283 could represent a win-win for them as a tx. for nonresponders or as a way to eliminate or reduce the need for ifn and/or riba or further shorten tx. times. They've done the preclinical combo work and some short-term P1 studies , and now they're starting a sizable P2 to optimize the combo regimen. A few hundred patients have been treated with the combo , and large numbers of serious AEs are occurring , including some deaths. Oh-oh. What will the FDA say ? Well , the combo trials will stop for sure , and that's perfectly reasonable , but out of concern for "patient safety" the FDA will also stop the monotherapy trials since one of these drugs is a killer and they don't have any idea which one it is. They need more toxicology studies , more time to elapse to detect AEs in previously treated monotherapy patients , etc. Both drugs are dead in the water , indefinitely , and the FDA is viewed by many as having averted a possible disaster. They're basking in the glow.

Now , in scenario 2 , VRTX and IDIX wait until the monotherapy drugs are approved , knowing that aggressive clinicians will do the combo anyway as it's an obvious way to try to deal with difficult patients. The same rate of serious AEs and deaths
occurs as in scenario 1 , above , but due to poor postmarketing surveillance and lack of interest at the FDA , the realization of a problem occurs more gradually and with more uncertainty. What does the FDA do now ? They send out a notice recommending against the combo usage ; they require a warning in the labels for both drugs , and monotherapy sales of both drugs live happily ever after.

IMO , many sponsors would see the above scenarios as a reasonable depiction of the current operation of the FDA : anal-retentive about safety before approval , and largely relieved of that burden by the approval "flush".

If the FDA was consistent with their actions regarding drug safety both before and after approval , and had good systems for post-marketing surveillance , then it would be in the drug sponsors' interests to do such combo studies ASAP , rather than gaming the system as they do now.

JMHO.