Ann: FDA Advisory Committee Sets Review Date for Remestemcel-L, page-709

As the PDUFA date draws near, shorters will be looking to capitalise on the possibility that Ryoncil will not be approved and that MSB will receive a Complete Response Letter (CRL). This is an asymmetrical bet so far as they are concerned because they would recognise that the FDA will more than likely issue an approval. But they will be looking for the very big payoff if it does not.

For reasons previously explained, I think the prospect of approval being refused is tiny given the AdComm 9-1 vote, Ryoncil’s risk-benefit profile, and the unmet need. There is no point going over all this again since the threads are full of well-reasoned and convincing discussions on the topic including in relation to manufacturing issues raised by the FDA in the lead up to the ADComm meeting.

But the other thing the shorters will be seeking to take advantage of is any delay in a decision. I don’t have any particular reason to think the FDA will not issue an approval by the PDUFA date. Even so, we need to be alive to the possibility that there may be some delay. Already in September the FDA has issued a number of approvals that lag the PDUFA date by between 2 and 10 days. That is why I would not regard a delay as a bad omen. If anything, I would say that delay is more likely to occur in situations where the FDA proposes to approve the application.

Now, let’s take a look at approvals, rejections, and delays in relation PDUFA dates for this month up to and including yesterday (25 September) which was the date of the last batch of FDA decisions.

Onureg
FDA accepted NDA for Onureg (in a new dosage form) in March and granted it priority review and a 3 September PDUFA date. No AdComm meeting was required. Approval was granted on 1 September. The applicant (BMS) is required to conduct a phase 4 trial as a condition of the approval.
(Timing of approval: 2 days early).

Detectnet
FDA accepted the NDA for Detectnet (a new molecular entity) in January (but without priority review) with a PDUFA date of 3 September. No AdComm meeting was required. Approval was granted on 9 September.
(Timing of approval: Delay of 6 days).

Gavereto
FDA accepted NDA for pralsetinib (Gavereto) (a new molecular entity) in early July with a PDUFA date of 23 November. Approval was granted on 4 September. This was a form of accelerated approval granted under the RTOR pilot scheme for oncology drugs. No AdComm meeting was required. The applicant (Blueprint Medicine) is required to conduct some further studies as a condition of the approval. That was expected given the accelerated approval pathway followed.
(Timing of approval: Almost 3 months early following accelerated approval pathway).

Terlipressen
Mallinckrodt received a CRL on 14 September in relation to its NDA for Terlipressen which had a PDUFA date of 12 September. As most here know, this followed an 8-7 AdComm vote. The drug’s risk/benefit profile is unimpressive, but it is directed to a significant unmet need.
(Timing of Rejection: 2 day delay).

EM-100
Eton’s application for EM-100 (a generic product) originally had a 10 August PDUFU date that was extended to 15 September. The company said the extension was due to a product name change. On 16 September Eton announced that it expected the FDA to communicate its decision “in the coming days”. EM-100 was eventually approved on 25 September.
(Timing of approval: 10 day delay)

Nucala
GSK was granted priority review for this drug (mepolizumab) in late May. Essentially, what is sought is a label extension. It’s not clear whether a PDUFU date was fixed but there was an expectation that this application would be dealt with by 26 September (assuming filing was completed 60 days prior to acceptance for priority review followed by the 6 month review period). Approval granted on 25 September.
(Timing of approval: 1 day early).

Libervant
Aquestive Therapeutic’s NDA for Libervant had a PDUFU date of 27 September. No AdComm meeting was required. A Complete Response letter was issued on 25 September. The company thinks the CRL can be addressed by provision of additional data.
(Timing of rejection: 2 days early).

I suspect that if the FDA believes its concerns are not addressable in the short term then it will drop the axe on or about the PDUFA date and issue a CRL. That is why I would suggest that a delay in the decision is more likely to be followed by an approval. So don't panic if we do not have a decision on the Ryoncil application by the PDUFA date.

We can all agree that MSB is now at a very significant inflection point. Personally, I do not think it is as important as the AdComm vote was because I think that vote virtually assured approval. But it is certainly a historic moment for the company and also for regenerative medicine more generally. I wish the Professor and his team, and all long-term shareholders, the very best of luck in the lead up to the FDA’s decision.

DYOR.