Replies to post #103585 on Biotech Values

[bladerunner1717]

Dew,

As I understand it, none of the adverse events showed up until at least five days after the participants left the clinic. In other words, there were NO adverse events during the clinical part of the trial, but only showed up some days after the participants left the clinic and, furthermore, only after the second evaluation after the patients left the clinic. The first evaluation after the participants left the clinic showed no adverse effects. What do you make of this? Could there be some exogenous event (e.g., people taking recreational drugs and/or using excessive alcohol--many young people enter these trials with a friend--that might account for the AE's?

Assuming the FDA lifts the clinical holds on both drugs individually, how do you think this will affect partnership discussions?

J.P. mentioned that there will probably be two new drugs entering the clinic before the end of the year. One is the NS5A inhibitor. What is the other?

Do you think there is much value in the IDX375 program, where IDIX said studies are continuing in the 4th quater?


Bladerunner

[oc631]

One of the three observed SAE’s appears to be explainable by gallstones

That certainly is Idenix's take on the matter but not mine. Considering the small size of the study (total of twenty patients), and the fact two other healthy patients experienced SAE's, nothing can be ruled out.

but two of the three SAE’s cannot be explained by any hypothesis other than an intracellular drug-drug interaction between IDX184 and IDX320

If this was true why did the FDA halt individual testing on IDX184 and IDX320? As you stated the DDI study came up clean and at this point nobody knows. IDX184 had previously shown unexplained tox signals at higher doses and IDX320 had an AE in 3 day POC testing. I'm not sure if latter event was listed as an AE but it was spoken about during the c.c.

[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).

[turtlepower]

These patients were supposed to be healthy. Would someone with gallstones actually have been able to enroll in the study? I'm a bit skeptical that someone with gallstones developed high liver tox during the treatment period from gallstones alone.

[mcbio]

IDIX @ Stifel (9/16/10)

1. Management believes it has strong evidence that IDX184 is not the culprit behind the side effects seen in the DDI study involving IDX184 and IDX320 (believe this was in reference to all of the studies conducted to date of 184 that have been clean). Management believes the culprit is either 320, the 184/320 combo, or the safety signal was just a fluke.

2. IDIX hopes to get written feedback from the FDA within 30 days (presumably formalizing the clinical hold in writing and not a lifting of the hold as the company still has a 28 day combo tox study to run).

3. IDIX hopes to be back in the clinic with 184 by the end of this year or early next year and hopes to "gently" move 320 forward in the clinic one more time at some point.

4. Regarding the three patients who experienced SAEs in the DDI study, there has been no evidence of drugs or alcohol and it's believed that these patients properly followed protocol. The patients with the grade 2 and grade 3 liver enzyme elevations are now back to baseline.

5. IDIX anticipates initiating additional HCV combo trials in 2011. There were no additional details provided, but I think we can safely assume that these trials won't involve the 184/320 combo.