I AM ALS letter to FDA asking for consistency in Advisory Committee evaluation of ALS treatments

Dear Commissioner Califf and Dr. Marks,

Thank you again for holding an Advisory Committee meeting regarding NurOwn on September 27th, and your recent decision allowing people living with ALS and other members of the public to participate in the meeting while on camera. We appreciate your efforts to recognize the community’s urgent needs for new treatments and to be heard.

I AM ALS and members of the ALS community are disappointed that the question being posed to the Advisory Committee fails to adhere to the same pattern of flexibility recognizing the significant unmet medical need of ALS as was the case for previous Advisory Committee meetings for ALS treatments.

The current question for the September 27, 2023 NurOwn AdComm is:

• Please discuss the data presented in support of effectiveness for treatment of mild to moderate amyotrophic lateral sclerosis (ALS), including consideration of the mechanisms of action proposed by the sponsor, biomarker data including neurofilament data, and the clinical data.

• Voting question: Do the data presented demonstrate substantial evidence of effectiveness for treatment of mild to moderate ALS?

The question the FDA posed at the Peripheral and Central Nervous System Drugs Advisory Committee Meeting on Tofersen was:

• DISCUSSION: Discuss the strengths and limitations of the available clinical data from the placebo-controlled study and long term extension regarding the effectiveness of tofersen for SOD1-ALS.
• VOTE: Does the clinical data from the placebo-controlled study and available long-term extension study results, with additional supporting results from the effects on relevant biomarkers (i.e., changes in plasma NfL concentration and/or reductions in SOD1), provide convincing evidence of the effectiveness of tofersen in the treatment of patients with SOD1-ALS.

And for the Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) Meeting on September 7, 2022, the question the FDA posed on AMX0035 was:

• Considering the new information submitted and the information presented at the March 30, 2022, PCNS meeting, is the available evidence of effectiveness sufficient to support approval of sodium phenylbutyrate/taurursodiol (AMX0035) for the treatment of patients with ALS? In addition to the prior and new evidence presented, you may take into account in your vote the unmet need in ALS, the status of the ongoing Phase 3 trial, and the seriousness of ALS.
• VOTE: Do the data from the single randomized, controlled trial and the open-label extension study establish a conclusion that sodium phenylbutyrate/taurursodiol is effective in the treatment of patients with amyotrophic lateral sclerosis (ALS)?

I AM ALS and the ALS community have emphasized the importance of NurOwn receiving a balanced and fair AdComm. Comparing these AdComm questions makes it difficult to believe this will happen and that consistent evaluations are occurring between the FDA agencies, CBER & CDER. The NurOwn discussion prompt and question do not have qualifying statements about ALS and its lack of therapies. Additionally, the word “substantial” within the question signals a higher threshold than those in the AMX0035 and tofersen AdComms.

With this in mind, we propose adding a consideration of “the unmet need in ALS” to the discussion prompt and replacing the word “substantial” with “sufficient.”

With sincere appreciation and hope,
I AM ALS