NurOwn AdComm: What happened? What’s next?

There have been a lot of conversations about NurOwn’s Cellular, Tissue, and Gene Therapies Advisory Committee (AdComm) meeting that occurred on September 27, 2023, the subsequent Biologics License Applications (BLA) removal, and its perceived irregularities. While much of the community is deeply disappointed in this outcome, the AdComm was not irregular per FDA process. 

Below we have listed the ways in which this AdComm did and did not deviate from the standard AdComm proceedings. This does not mean that the FDA’s current review process serves people living with neurodegenerative and rare diseases well. To be clear, it doesn’t. The ALS community and I AM ALS will continue strategizing and working to have a more suitable pathway. 

Here are the ways in which the NurOwn AdComm was typical:

1. FDA advisory committees typically provide one hour for public input with three minutes for each speaker, as was the case for NurOwn. There have been exceptions to the three-minute time slots. For example, CDER has given people living with ALS five minutes instead of three.
2. The FDA typically releases the docket of material two days before the AdComm and did so this time too.
3. AdComm members are not typically experts specifically in the disease being discussed.
4. The FDA uses a lottery system to choose speakers from a pool of interested applicants for the open public hearing if there are more prospective speakers than speaking slots, as they did with NurOwn. 
5. The FDA and the drug sponsor (BrainStorm) each had the standard 85 minutes to present their interpretation of the data and answer questions. 
6. Chemistry, Manufacturing, and Controls (CMS) is a vital part of drug development that the FDA always considers as part of the approval process.
7. Unfortunately and typically, public hearing testimonies and written comments are excluded from the AdComm’s decision making process. 
8. The AdComm’s format does not typically allow for drug sponsors (BrainStorm) to respond to questions from the members directly before the voting occurs and outside of their formal presentation session. 
   1. Note: while this is true, we would still like the manufacturer, BrainStorm Cell Therapeutics, to provide those answers to the ALS community. We will be asking BrainStorm to answer those questions publicly.

Here are the ways in which the NurOwn AdComm was atypical:

1. The FDA typically develops a list of questions for each AdComm for the members to answer. The questions the FDA provided for the NurOwn AdComm set a higher bar for approval than other ALS AdComms. This is even more absurd if you consider the FDA’s Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry document and its policy of regulatory flexibility for ALS therapies.
2. Real-world evidence (RWE) is sometimes considered as part of the data review, but was not considered by the NurOwn AdComm because RWE was not part of BrainStorm’s application. The FDA cannot consider RWE that was not submitted by the manufacturer. I AM ALS is advocating for the passing of the BENEFIT Act to ensure transparency in how real-world evidence from trial participation and broader patient-reported outcomes are considered in the FDA approval process.
3. The AdComm members did not respond to the follow-up question posed to them by the FDA. The prompt was “If the answer to Question 2 is no, please discuss potential designs for a trial to demonstrate substantial evidence of effectiveness for MSC-NTF for the treatment of mild to moderate ALS.” The answer was no and this was not discussed. Now that BrainStorm has withdrawn its application, we want BrainStorm to know how this trial design could have been better to measure NurOwn’s impact on ALS progression.

I AM ALS facilitated a town hall with BrainStorm on November 7th, 2023. You can watch the full event recording here: