A Citizens' Petition filed with the FDA is seeking accelerated approval for NurOwn, Brainstorm Cell Therapeutics' mesenchymal stem cell therapy for amyotrophic lateral sclerosis (ALS), based on what advocates describe as unprecedented survival and respiratory data from clinical trial participants and real-world evidence.
The 309-page legal document presents survival data that petition supporters argue meets or exceeds the evidence supporting accelerated approval of dozens of cancer therapies. Key findings include 100% five-year survival in the Expanded Access Program (EAP) compared to 20% in natural history, with a p-value of approximately 0.000335 (one-sided) or 0.000671 (two-sided).
Compelling Survival and Respiratory Outcomes
The petition documents a median of approximately 7-year tracheostomy-free survival (60-103 month range) in EAP participants versus 30 months median in ALS natural history. Additional data shows progression-free survival ranging up to 17 months, long-term slowing of ALS progression of up to 85%, and halting of respiratory decline in some patients.
Particularly striking is the time-to-non-invasive ventilation (NIV) data, with NurOwn recipients showing a range of 5-8+ years compared to 15-27 months in natural history. The petition notes that NurOwn recipients with bulbar onset lived approximately 3.5 years longer than the median in ALS natural history.
Clinical Observations Support Patient Reports
Dr. Danielle Geraldi-Samara, a neurologist with over 15 years of ALS experience, documented her clinical observations of NurOwn recipients in her practice. In her FDA public comment, she stated: "I have seen the full breadth of clinical constellations playing out over time. What I have not seen, though, is anyone with significant functional improvement from a declining baseline; I have not seen patients rise from plateaus. It does not happen in the natural course of ALS. It did happen with the introduction of NurOwn."
Dr. Geraldi-Samara reported observing "patients nearly immobile who gained some functionality in their gait, patients with severe dysarthria become intelligible, patients who could not manage the fine motor skill needed to button or zipper, finally able to dress independently."
Case Study: Kade Simons
The petition includes detailed data from Kade Simons, who died of ALS in August 2024 at age 26. Kade received three doses of NurOwn from July to November 2019 and experienced what his treating neurologist described as unusual clinical stability for someone with multi-loci ALS onset.
According to the petition, Kade had symptom onset in three regions concurrently and was initially a fast progressor, losing 1 point per month on the ALSFRS-R scale before receiving NurOwn. His ALSFRS-R score had declined to 34 by the time he received treatment in July 2019. Following NurOwn treatment, his progression slowed dramatically from more than 1 point per month to 0.16 points per month.
Kade lived "trach-free" for 78 months (6.5 years) from symptom onset versus the 2-year average for bulbar onset ALS. He did not require non-invasive ventilation until his death, far exceeding the 15-month natural history for fast progressors and 13.5 months for people with bulbar onset.
Expert Clinical Opinion and Trial Unblinding
The petition cites opinions from experienced ALS clinical trialists including Dr. Robert Brown of UMass Chan School of Medicine and Dr. Anthony Windebank of Mayo Clinic, who stated that a "significant number" of people had a "clinically meaningful" response to NurOwn, with some experiencing progression-free survival and functional improvement.
When the Phase 3 trial was unblinded after the Advisory Committee meeting, Dr. Geraldi-Samara noted that "almost without exception, every one of my patients accurately predicted if they received NurOwn or placebo." The petition states: "When people are dying, they know when a drug helps them live. When people are becoming paralyzed, they know when a drug helps them move again. And when people can't breathe without a non-invasive ventilator, they know when a drug helps them breathe again."
Mechanism and Manufacturing
NurOwn is manufactured from patients' own mesenchymal stem cells harvested from bone marrow aspiration. The cells are processed in a laboratory and enhanced to release neurotrophic factors. When injected directly into the cerebrospinal fluid, the modified stem cells deliver neurotrophic factors and immunomodulatory cytokines to motor neurons damaged by ALS.
Regulatory Strategy and 21st Century Cures Act
The Citizens' Petition relies on provisions of the 21st Century Cures Act, which encourages the FDA to consider real-world evidence and patient experiences in regulatory decisions. The petition argues that in "100% terminal and heterogeneous rare diseases, every story matters and every type of evidence matters."
Petition supporters contend that the FDA's focus on primary endpoints alone resulted in a Type II statistical error, overlooking the totality of evidence including responder data, biomarker findings, patient experiences, and clinical observations. They are requesting approval with a Phase 4 post-marketing study to allow broader access while continuing to collect safety and efficacy data.
