ALS is a devastating, incurable disease that urgently needs innovative treatments and cell therapies have potential, but so far data on the most prominent candidate cellular drug, Nurown from BrainStorm Cell Therapeutics, have not convinced the FDA to approve it.
The agency has wanted to see more data and hopefully more convincing data.
Now an ALS patient group has sent a letter to the FDA making the case for the agency to go ahead and approve Nurown for ALS.
Patients request Nurown approval
What will FDA Commissioner Marty Makary and CBER leader Vinay Prasad do in response to the patient petition? I see this as a very challenging situation for them to navigate.
From the request:
“Backed by a decade of real-world data from the NurOwn trials and Expanded Access Program (EAP), the 309-page Citizens’ Petition details the unprecedented survival, respiratory, and biomarker data for the FDA’s consideration. The new evidence is supported by testimony from top ALS neurologists who were the trial’s principal investigators, and the “totality of the evidence” from the Phase 3 trial. And, it aligns with real-world evidence where trial participants (now-unblinded) and their treating neurologists have proclaimed that NurOwn improves how people with ALS “feel, function and survive.”
The petition cites various kinds of data that on the surface are suggestive that Nurown may have benefits for some ALS patients. It mentions data from the EAP. Biomarker data too.
There was some possible improvement in overall survival and respiratory function in a small group.
The letter advocating for approval sees these data as encouraging enough for approval.
Conditional approval requested
The patients ask for “conditional approval”, but the FDA has no conditional approval system like Japan for regenerative medicine products.
Perhaps they mean accelerated approval? Interestingly, they used the phrase “conditional approval” because some people want the FDA to adopt such a system too. Would that require new legislation?
Not surprisingly, BrainStorm Cell Therapeutics is upbeat about the patient petition.
Reasons the agency has wanted more data before
I get the urgency here.
However, there are good reasons that the FDA has wanted more data than what the patient groups cited in their petition.
It’s a big deal that the BrainStorm Cell Therapeutics phase 3 trial failed to meet its primary endpoint.
The argument for Nurown approval in the letter rests heavily on post-hoc analyses as well as real-world experiences of doctors and especially patients including in an expanded access program (EAP). These experiences are important and must be respected but can have limitations. For example, the EAP participants may not be representative of ALS patients more generally. A group with less severe cases of ALS may be more amenable to treatment.
ALS Association view
The ALS Association has been cautious about Nurown and expressed concerns about the data. For example, they wrote:
“After BrainStorm shared that its Phase 3 trial of NurOwn did not meet its primary or secondary endpoints, we have consistently requested access to the full data package so we could try to better understand its effect on people living with ALS. The amazing testimonials we have seen online do not align with the data that BrainStorm has shared with us or has been published in peer-reviewed publications.”
I tend to agree with them and take their views very seriously.
What will Makary and Prasad do regarding the ALS patient petition?
So what will the FDA do about this petition?
FDA Commissioner Marty Makary and CBER Director Vinay Prasad recently have emphasized real-world data.
The patient petition understandably points this out. So on that level, one might think that the agency could reverse course from its past decisions here and potentially give some kind of approval for Nurown. From the petition:
“And as Commissioner Makary recently said at the Gene and Cell Therapy Forum, there is value in learning from “n of 1” cases. Combined, the EAP “n of 10” and the right to try “n of 1” illustrate compelling and consistent, dose-dependent evidence of efficacy.”
On the other hand, Prasad has been critical of past FDA approvals that were granted with what he seemed to think were not enough data or data that weren’t compelling enough.
Wait for more data?
Also, the agency recently okayed a Phase 3b ENDURANCE clinical trial for Nurown. The FDA might decide that the safest route might be to just wait for those data before making such a major decision.
The voluntary withdrawal of the Amylyx ALS drug Relyvrio is relevant and somewhat sobering here. If the FDA were to approve Nurown now and then the ENDURANCE trial did not confirm benefit later, it could be a major setback.
Yet, ALS is so devastating that patients and families understandably are not inclined to being told to just keep waiting for more data. I can see Makary and Prasad (and importantly, perhaps RFK Jr.) being sympathetic to that in deciding about the petition.
It is possible that Nurown benefited a few ALS patients in trials or the EAP, while not helping others. We’ve seen that kind of profile with other emerging regenerative therapies, which makes for complex trial data.
Overall, this ALS patient petition on Nurown is going to be a tough test for Makary and Prasad as well as the FDA more generally.
It may become irrelevant soon. The 4th Circuit (albeit a 3 judge panel not the entire circuit) just ruled Definitively, that the Federal statute which created the “preemptive” nature of an FDA approval, can not be enforced to prevent a State from it’s historical and superior obligation to protect the health and well being of it’s citizens. So overturning decades of law and practice, a State MAY ban a drug that has FDA approval. This would also almost certainly mean the reverse is true. A State may approve the use of a drug, WITHOUT FDA approval, under the same health and welfare standard. This administration has been trying to create a permission structure which weakens all federal regulatory power. While everyone is (rightly) focused on the people they have put into decision making positions at very agencies, THIS is the real attack. It is also btw, something the Goldwater Institute has been trying to bring before the Supreme Court for years. This looks like the vehicle that gets them in the door.
Richard, I don’t know if the reverse is necessary true but maybe so.
A perspective for the FDA to consider. Nurown is the only ALS therapy delivered intrathecally. The only therapy that reversed and stopped progression, where EAP participants are still trach-free all these years later. It could be coincidence, but the data points to an effective method.
Please read this story about my son’s experience with 6 consecutive Nurown treatments and a latent 7th delivered late due to Covid. I believe the FDA did something unfortunate in September 2023. This 2025 Citizens Petition asks the FDA to review what was done in the lead-up to the Adcom, the Adcom itself, review the EAP data, and take a hard look at all of the people still thriving despite the time lapse since last dose. I believe we owe that to the ALS Community.
https://www.accessnewswire.com/newsroom/en/healthcare-and-pharmaceutical/navy-pilots-with-als-fight-for-access-to-the-stem-cell-therapy-that-c-1048025
I don’t think it’s that tough of a call for FDA.
New HHS management has been talking about speed and efficiency for approvals. The Brainstorm data have already been been reviewed thoroughly the old slow way. Doing another review of the same data quickly isn’t going to generate a more favorable result imo.
We’ve known for years that Brainstorm needs to run another trial. Unfortunately that has not happened. They did not meet any of their efficacy endpoints in the old trial. You can talk about the positive anecdotes, but our regulators need some solid data on which to base an approval.
This therapy has frustrated those dealing with ALS for years. As with any therapy that benefits some, we need for the company to drill down and figure it out so that we can let the FDA do its job based on solid trial data.
People with ALS deserve better than the rearrangement of old data in press releases.
As much as I dislike fb, there is an interesting group there — “ALS Clinical Trials and Research” It offers some interesting analysis and perspectives.
Thank you for covering an important topic.
@ALSadvocacy, I tend to agree with you but I think this FDA could do something unfortunate here.
The Nurown and FDA saga continues, there’s a deep history here.
I’ve talked extensively with Mike, who runs this group:
(No More Excuses! ALS Watch Dog Group – https://www.facebook.com/groups/156722665270133 )
From what he told me and if my memory serves me correctly, he’s an ALS patient himself, did the trial but received placebo. There are about 15K people in that group, some of which believe they did not receive placebo, and improved. Those patients made videos and posted in the group, making everyone pretty excited, until the trial somewhat flopped.
I’ll ask the group owner to comment here, but he mentioned to me he felt the trial was designed poorly. Following this, the ALS Association clarified their stance here: https://www.als.org/research/als-research-topics/drug-development/our-position-supporting-approval-experimental/our-position-nurown
I’d also like the group owner to comment on his stance on this non-profit, he has a few words to say on it.
Lastly, if you are in the group long enough, you will sadly see patients come and go. A few weeks ago, one ALS sufferer’s home burned down with them inside, unable to escape. It’s a devastating condition with no real answers. The FDA has their hands full on this one.
@EV Tech,
Thanks for the info & perspectives. Given all they’ve said, I don’t think it’s easy for the FDA to just say no here or even maybe to say wait for the 3b data, but if they approve Nurown now they are also taking a big risk.
This should 100% be approved either fully or in a “conditional approval” like Japan. It is high time that the FDA stop limiting the options for people suffering from incurable diseases like ALS. It is their life and their bodies and the drug has shown to be safe and effective. As adults, it should be their choice. I hope that after this approval it opens the door for many other drugs in Phase II and III