Innovation Pharmaceuticals Inc (IPIX)

[TOB]

Over the next 2-3 months we can expect

Kevetrin concluding/ conclusion Phase 1.

He must be telling us that the current cohort is the final one and that there will be no 12 patient final cohort due to the trial ending before Kevetrin reached the MTD. I didn't realize that this was possible. -JB3729

They have flexibility to make changes in the protocol, some via the study site Institutional Review Board, some changes need FDA approval.

Writing in an email is not always as definitive as a PR. Obviously PR's get reviewed and edited, probably by more than one person. So I'm skeptical if he meant Kevetrin P1 is wrapping up so soon. (But certainly possible and that is how the email was written.)

Personally I'm not bothered if additional cohorts are enrolled as I'd be happy to see them continue to higher doses. Efficacy may increase with dose. Perhaps dramatically so.

It would surprise me if they stopped the trial without determining the Maximally Administered Dose (MAD). But there could be compelling data to support such a move. I doubt it would be impatience however. Certainly not by the scientists, except in the case of futility.

All indications so far that suggest preliminary signs of Kevetrin efficacy, not futility. This is also a dose escalation safety trial, with secondary efficacy outcome measures. With no alternative standard of care available, there is no reason to halt for futility. I could see a sort of halt for efficacy, where they have data that indicates they should be dosing more frequently. So either morph the trial into a Phase 2 by seeking FDA approval, or halt it to get on with a Phase 2 dose optimization trial, which could have some dose escalation in the design.

We can consider that this trial is for patients without other treatment options. So if Kevetrin is working, and the PK data suggests more frequent dosing is needed but that the dose level is sufficient, it makes sense to speed getting to that point.

Alternatively, there was that one Dose Limiting Toxicity (DLT). Unless it was a fluke, it is reasonable to expect 2 DLTs to occur at a dose level not too much higher.

In this trial example below I posted back on 2/4/13 - also a Dose Escalation Trial done at Dana Farber by Dr Shapiro and presented by him at ASCO - you'll note the 400mg dose level had one DLT. They then enrolled an additional 6 patients with no additional DLT occurring, so they continued up two dose levels.

600mg had the initial 3 patients with one DLT, so they enrolled another 3 patients. No more DLT.

So they went up a dose level to 900mg. There they had 2 DLT and declared Maximally Administered Dose (MAD)

They then further expanded the 600mg cohort (it's not a new cohort, it's an expanded cohort) with 10 additional patients with no more DLT. This was then determined as Maximum Tolerated Dose (MTD) (Note that the Phase 2 design may well have had some dose increases above 600mg, but below 900mg, as they sought to determine the therapeutic dose.)

So again, if not a fluke, the one DLT we saw so far with Kevetrin suggests that the Maximally Administered Dose (MAD) should be soon.

(Click to enlarge. From a 3+3 Phase 1 Dose Escalation Trial)