Biotech Values

[mcbio]

Re: IDX184/320 clinical hold

IDIX CC post-mortem: One of the three observed SAE’s appears to be explainable by gallstones, but two of the three SAE’s cannot be explained by any hypothesis other than an intracellular drug-drug interaction between IDX184 and IDX320. (The completed DDI study showed no drug-drug interaction between IDX184 and IDX320 in terms of PK and plasma concentrations.)

Both individual drugs have had clean safety profiles in humans and animals as monotherapy, and IDX184 has had a clean safety profile in combination with SoC in HCV patients. (IDX320 has not yet been tested with SoC.) Thus, it appears likely that the individual programs for IDX320 and especially IDX184 will be able to move forward when the clinical hold is lifted.

Very disappointing news today. I haven't had a chance to listen to the CC yet, but will when it's posted on IDIX's Web site.

Did management say which of the two arms experienced the SAEs? I know the dosage of IDX184 and IDX320 were the same in both arms, but the treatment order was reversed in each arm. I guess that likely wouldn't make much of a difference since we're ultimately not talking about a difference in dosage for either drug. But perhaps IDIX will be able to go forward with a lower dose of one or both drugs in combo in the future.

I do agree that at least the individual programs will likely be allowed to move forward when the clinical hold is lifted given that the inidividual safety profiles of each drug have been clean to date.

However, the IDX184+IDX320 combination program is probably dead, IMO, even if the combination animal-tox study IDIX is now starting turns up nothing untoward. I don’t think the FDA will allow these two drugs to be given together when there are many other combinations of DAA’s that can be tested instead. Since IDIX has made all-oral combinations its raison d’etre, a lot of IDIX’s intrinsic value may have evaporated today.

I do think you're probably right, unfortunately, that the 184/320 combo is probably dead given this news. We'll see if a lower dosage can be utilized or if some other news comes out that helps mitigate concerns to some degree, but I do view that as unlikely. That said, we still have the drugs inidividually available for partnering. I guess the biggest question is if a prospective partner would now be scared that one or both drugs might also have issues if they inserted them into their own HCV cocktail. I.e., are these safety issues today just something relegated to a 184/320 combo solely, or is there a legitimate chance they could crop up again in a combo of 184 or 320 plus a partner's HCV cocktail?

I agree that IDIX lost a lot of intrinsic value today given this news and their focus on an in-house HCV combo, but that is presumably now accounted for in the price drop and there is obviously still IDX899 outside of HCV. Also, I think we still have the possibility of an IDIX in-house HCV combo given the proprietary NS5A inhibitor plus either 184 or 320. And, again, I can't imagine that at least one of 184 or 320 won't be able to be licensed if the clinical hold is ultimately lifted on individual testing (I think it will be).