MSB to dispute FDA finding in Type A meeting, page-305

@ 6:30 for the proposed adult trial, they said they were goin to use an endpoint taking into consideration survival, because survival is really the primary endpoint they are focusing on.

That is where I understood that they are pivoting to using the 28 day ORR as a surrogate endpoint, and the adult trial will be using a primary endpoint taking into account survival.

I mentioned I still felt uneasy about the chances of accelerated approval, so I thought I'd elaborate on that. Firstly, although we can see what MSB are trying to do here.. it really is a plan B and they are trying to take an unconventional route to approval.

With a positive light on the situation, some are looking at this as if the FDA is encouraging MSB to go down the path of accelerated approval. I outlined why I thought they would be doing that i.e. unwilling to make the leap to full approval and efficacy sign off on a single arm study, but basically covering their back side if it turns out Ryoncil doesn't work.

The opposite view of the situation is that there are some people in the FDA (or outside of the FDA) who do not want this treatment made available and/or delaying it as much as possible. In which case those in power and influence within the agency could very well stand their ground and throw the rule book at MSB at this Type A meeting and simply say that you missed your opportunity for accelerated approval and that in pursing such a path would be seen as undermining the entire FDA approval process. In which case, MSB either walk away.. or conduct that adult study prior to approval.

While there is an example of a backflip from the FDA with Sarepta where accelerated approval was granted after a CRL (issue was on safety grounds though), these dispute resolution meetings typically go against the sponsor .. this journal (a little dated) only shows 16% success

dispute resolution journal

"FDA’s Center for Drug Evaluation and Research (CDER) received 137 appeal issues for fiscal years 2003 through 2014. However, sponsors can appeal the same issue multiple times, and each is considered a unique appeal; CDER received and analyzed 173 of these unique appeals.

Of these 173 unique appeals, CDER accepted 140 (81%) for review and refused to accept for review 25 (14%). Eight (5%) were withdrawn by the sponsor prior to CDER making a decision whether to accept the appeal for review.

Of the 140 unique appeals accepted and reviewed, CDER granted 23 (16%) appeals and denied 117 (84%)."

Another point making me feel a little uneasy is that it also sounds like MSB are using the adult trial as a bargaining tool... whilst I don't disagree with that, it can have the opposite desired effect on the agency. This approach may push the wrong button and the FDA may get even more defensive and call their bluff.

All this sounds unreasonable and illogical.. but after what happened this week, it is unfortunately very plausible.

While am sharing my thoughts on uneasiness, my intention is not to scare people on this forum. It's my view only and please do not take it as investment advice.

To balance it out though, I am still optimistic that Ryoncil can get approved through an accelerated pathway. But it requires the FDA to be co-operative and there needs to be a Director at the FDA at this Type A meeting that is willing to offer MSB a shot at accelerated approval. That is the first hurdle, and if they clear that at the end of this month.. I would start pricing in the chance of a successful accelerated approval.

Underpinning my confidence is the 9-1 ODAC vote, because from what I've come across.. when a company disputes a CRL, the FDA can suggest an advisory committee as a potential resolution to the CRL issue in question. But because the ODAC has already been sat and result is in hand, then all MSB need is to re-submit the NDA with agreement from the FDA that they are chasing accelerated approval with all the strings attached... and it will be looked at by the FDA in that lens, rather than full approval.

I'm going to let others pick up the discussion from here... I feel I've laid out my thoughts and will drop back into the forums here and there, apologies in advance if I don't respond to all questions directed to me. Life outside of HC is very busy at the moment.

Goodluck all