The CHMP meeting will take place next week April 23-26, we have no idea what day exactly is SRPT meeting, (Update 04/23: today the CHMP published this week agenda and SRPT Oral-Explanation set on 04/24 at 8:00 EST) . Usually after the Oral-Explanation the CHMP will ask the applicant representatives to step out from the room and they will have a “trend vote” that will be passed to the applicant, while final vote expected to follow in the next CHMP meeting in May.
The “trend vote” is actually the hint from the CHMP right after the Oral-Explanation, if the CHMP will consider a POSITIVE opinion or not. If “Negative” opinion is expected, then usually companies choose to withdraw the application.
Some companies choose to update their investors via PR regarding the “trend vote” but others are waiting for the final vote, we have no idea what is SRPT decision, if they will PR the outcome or wait till May.
In case SRPT choose not to PR the CHMP “trend vote” after the meeting, then we have to wait till the Q1 earnings call on 05/03 to see if they will update the market with the CHMP “trend-vote”. Or we have to wait till the next CHMP meeting on 28-31 May, 2018. And on Friday 06/01 at the official CHMP Highlights we will see if SRPT got positive or negative opinion!
Lately we had several examples of companies PR following the CHMP Oral-Explanation meeting, like Puma Biotechnology (PBYI) with PR of the negative trend vote:
Portola announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has communicated a positive trend vote on the Marketing Authorisation Application (MAA) for andexanet alfa, a Factor Xa-inhibitor reversal agent, and a negative trend vote for betrixaban, an oral, once-daily Factor Xa inhibitor.
SRPT will have 10 representative including some top DMD KOL’s taking part in the Oral-Explanation, they will try to convince the CHMP how the totality of data support therapeutic benefit (although it’s unclear the extent to which EU regulators will adopt a “totality of the data” approach for this filing). SRPT will use all the data they have from over 4 years long trials vs. the natural history data, also will use the pulmonary analysis from the non-ambulant patients trial to show that DMD is not only about walking but also patients Quality-of-Life.
SRPT’s CEO Doug, at the Cowen fireside chat on March 12 gave details of the data they will use to support their EMA’s MAA .
We have done analytics on the regional study, we had 201, 202, with PROMOVI we did interim analysis and we’ve done this so-called 204 study, which is non-ambulatory. So significant number of patients all in. We’ve compared versus the synergy database which is kind of the current goal standard for registries as well as for pulmonary function. And we’ve done on a down to a patient level basis and some of it is very longitudinal. So with 201, 202, I think it goes out nearly four years and across all of those to a very significant nominal P-value there was a significant diminution in pulmonary decline versus natural history for eteplirsen. With that all that said, I have got to get it published, it’s truly meaningful and we are in the process of doing that now.
Doug explained well what they are looking for from the CHMP meeting.
Regarding Europe, we are in the process right now. We are tracking to an oral explanation in late April. We should have an answer before the middle of this year. The standard is different in Europe than in the U.S. as I have said before, we have to prove functional outcomes in the U.S. and we’ve won on our surrogate endpoint, it is reasonably likely to lead to clinical benefit. From my perspective, the teams done a brilliant job of putting together all of the compelling data that we have and updated it and so I think it resonates and I think anyone that is willing to look at the totality of evidence should see that this therapy does a lot of good and it’s very safe. But it is a very challenging standard and I cannot say with certainty what’s going to happen until we get through this process and get through the oral explanation.
We have to consider this event as a binary event, a coin toss, from one side Eteplirsen approved in the US & patients stories keep coming with young men at age >17 years old and keep walking vs. the real life natural history where most boys in wheelchair at that age, but on the other side, the dystrophin production alone have historically not been acceptable by the EMA, and EMA’s view on lung function as an endpoint is unclear yet.
We have to consider reducing risk by hedging our position with put options or reducing the position size, as the EMA is not a done deal and in case of application withdrawal I expect a drop of at least 5 to 10 points in the share price (some are already baked in as the street is already expecting a negative outcome), then we have to wait till the next catalyst. the Gene-Therapy safety and biopsy data from first 2 patients during June, or from 3 patients if SRPT decide to wait for more data, then during July for a share price recovery.
1. Long term investor might ignore the EMA outcome and wait till the gene-therapy results. In case of positive opinion they will enjoy another spike in the share price even before the gene-therapy results.
2. Short term traders might sell part of the position to reduce risk and keep part in case of a positive opinion and spike in the share price towards the $90’s, and in case of negative opinion, they can buy back the shares they sold at lower price.
3. Investors might buy put options to hedge their full position, can pick weekly April 27th put options if they believe SRPT will PR the trend vote the same week, or more expensive puts of June 01st that will cover the CHMP May meeting highlights for sure.
4. Investors might sell part of their position and buy instead August call options that will cover both the EMA decision and the gene-therapy results, but with options they know exactly the amount they are putting at risk.
There are many options out there, so each one of you have to manage his risks, depending on his/her risk tolerance & the time frame you are working with.
After the CHMP opinion, the catalysts keeps coming, next we will wait for the gene therapy results from the NCH study, Dr. Mendell’s first dosing was on 01/04 and the biopsy will be taken 3 months post the therapy, which lead to around 04/04 as the biopsy day, I assume SRPT already have the biopsy results as it takes ~2 weeks to get biopsy results, next biopsy will be around 05/15 so by end of May to early June SRPT will have the biopsy results from 2 patients and if they decide waiting for the third biopsy around 06/15 then the results will come around early July.
Most likely SRPT will present the results during the 2018 PPMD Annual Conference on June 27 – July 1, 2018. The question will be, would SRPT present the gene therapy trial safety and biopsy results from the first 2 patients or wait till the third biopsy comes in?
Disclosure: The Author is Long SRPT