Innovation Pharmaceuticals Inc (IPIX)

[slcimmuno]

Proof of Concept (PoC) studies -- the exact right way to go about studying a drug candidate's potential, esp for smaller companies like IPIX with limited resources but Big-Time potential.

See below. Earlier posts.

First deal inked and everything changes.

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How statistics, powering, doesn't really matter at this stage. More validate the drug enough to advance it onto the next (pivotal) stage. The Endoscopy images will prob tell the tale of the tape. Many Big Pharmas have shied away from including it in their Phase 2s but not CTIX. They need to know if it works or it doesn't -- now not later.

http://drugbaron.com/phase-2a-proof-of-clinical-concept-trials-the-single-most-important-determinant-of-rd-efficiency-in-drug-development/

The future of the pharmaceutical industry depends on improving our approach to the early Phase 2 trials. After all, three of the most important decisions relating to a drug product candidate are founded on the data emerging from Phase 2a trials: do we believe it will work in pivotal trials with regulatory end-points that will likely cost hundreds of millions of dollars? What should be the design of those pivotal studies? And perhaps most critically, will this drug likely offer a sufficiently differentiated profile to be a commercial, as well as regulatory, success?

A product candidate clearly needs positive answers to all these questions to progress.

Actually, a product candidate ought to need these three ticks to progress.

The recent slew of high profile phase 3 failures, with Lilly in the vanguard, suggest that at least in some quarters this critical gatekeeper function is not being efficiently applied.

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Fortunately, there is another solution: stop treating Phase 2a studies as “mini Phase 3” trials. Too often, a surrogate end-point is selected and the trial design is centred around a statistically significant change in that primary end-point (just exactly as a Phase 3 trial is designed only to demonstrate, beyond doubt, that the single primary end-point has been modulated). The dominant concern is to “protect” the statistical power of the trial by focusing exclusively on the primary end-point in the a priori analysis.

It is entirely right and proper that such a “statistical gold standard” applies in pivotal trials. It is the only way to be sufficiently certain of the benefit of a product candidate. To lower that bar would risk public health. But it is entirely wrong to take that approach in Phase 2.

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In effect, such a study design trades off formal statistical power for a much wider appreciation of the effects of the drug on the whole organism. It is very much the right choice to make such a trade. Instead of looking with absolute precision through a pin-hole, one gains a fuzzy view of the whole landscape. Asked to identify the object of a photograph, DrugBaron is certain most readers would perform much better with an out-of-focus version of the whole image than a perfectly focused single pixel – even if the focus was truly terrible. If you don’t agree, try the experiment!

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In effect, we had designed a “safe experiment in humans” rather than a “clinical trial”. The results could never be used to support the approval of the product – but that was never the intention (and, indeed, is never really the objective of a Phase 2a study). Instead they did what a Phase 2a study is intended to do: inform the design of the next clinical trial, both in terms of selecting the right patients and the right end-point, and at the same time de-risk continued investment in the drug.

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Smaller biotech companies are typically much more innovative in their early stage clinical trial strategies. That innovation is driven by a need to convince a pharmaceutical company to buy their programme, rather than from a need to satisfy the regulator at that early stage. The regulator will need to be satisfied, of course – but not yet.

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Proof of Concept trials

Another major part of the Novartis strategy is greater use of proof-of concept trials, in place of the traditional phases I to III progression. The new approach is particularly useful in oncology, where far earlier targeting of those patients likely to benefit most has reaped enormous rewards, cutting costs and producing proof of a drug’s efficacy (or otherwise) far earlier.

Novartis is now shifting towards a model of selecting patients most likely to benefit from the drug for the Phase I trial, and then following this up with a proof of concept trial which serves as the pivotal trial submitted to regulators. (see illustration).

Naturally this approach requires agreement from regulators about the validity and robustness of data from these trial designs, but the FDA in particular is now open to accelerated trial programmes. These trials often produce less mature data than traditional Phase III programmes, but this is partly offset by the science behind the design i.e. the targeting of patients based on their genetic profiles.

Proof of concept trials can’t reduce the failure rate of compounds in development, but they do shift any potential failure rate to earlier stages of the drug development process, saving huge amounts of time and money.

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