1) Orphan drug status has advantages in terms of extending patent protection--by specifying a subset of severe TBI patients, one can try to manipulate the putative market size into the range acceptable as an orphan drug--Cypros has taken that tack with Ceresine. I find the argument unconvincing--TBI is a big market.
2) Treatment IND status complicates enrollment into blinded trials: if you have a relative with TBI, would you accept the chance of them receiving placebo, if there was a Tx-IND alternative guaranteeing the drug? So I see no advantage there.
3) Since ICP is a standard medical parameter whose control is central to the current tx of TBI, since the FDA is supposedly increasing its acceptance of surrogate markers, ICP would be a prime candidate. It has the advantage of being objectively measurable. However, IF the FDA were to do so, either functional outcome OR mortality would still have to be a secondary endpoint, thus they would still have to enroll enough patients to have a shot at statistical significance there. I would expect the TBI trial to be geared towards a total enrollment of 800-1000, perhaps with an interim analysis at 400-500, where one might find significance (or they could use a safety monitoring board to periodically, independently, appraise the data).
4) In reply to Omer Shvili's comment; it is true that the 48mg cohort was quite small--perhaps a dose-related effect will yet emerge, but the 200mg dose is not that much beyond 150, I am not expecting one. It also means that PARS lacks a parameter that the FDA likes to have; the minimally effective dose. If 48 and 150 end up seeming to be equal in efficacy, the FDA could ask whether 24, or 36, might also be effective. However, since there is no toxicity/side effect issue that clearly must be avoided, the question is less pressing. NeuroInvestment (www.neuroinv.com) |
