A coalition of ALS patients and family members has filed a comprehensive Citizens' Petition with the FDA requesting approval of NurOwn, a novel stem cell therapy that combines autologous mesenchymal stem cells with neurotrophic factors. The 309-page petition, backed by a decade of clinical data, presents what advocates describe as unprecedented survival and efficacy evidence for treating amyotrophic lateral sclerosis.
Revolutionary Stem Cell Approach
Developed by BrainStorm Cell Therapeutics, NurOwn uses a patient's own stem cells enhanced with neurotrophic factors to deliver therapeutic compounds directly to damaged motor neurons. The therapy functions by delivering "nano-packages of neurotrophic factors and immunomodulatory cytokines" to dying motor neurons, with trial participants reporting rapid symptom improvements within days of treatment.
The petition details profound clinical responses, with participants experiencing halting of symptoms including fasciculations, cramping, and clonus, along with functional improvements. Extended dosing through the Expanded Access Program (EAP) demonstrated the therapy's ability to slow ALS progression, improve function, restore breathing capacity, and extend survival.
Unprecedented Survival Outcomes
The petition presents survival data that petitioners describe as "unprecedented in ALS clinical trial history." Key findings include:
- Five-year survival: 100% in NurOwn EAP participants (n=10) versus 20% in ALS natural history
- Extended tracheostomy-free survival: 7-year median survival (range 5-8.5 years) compared to 2.5-3 years in natural history
- Progression-free survival: Ranging from several months to 17 months when patients received NurOwn treatment
Dr. Anthony Windebank of Mayo Clinic, who presented clinical trial data at the 2023 FDA Advisory Committee meeting, testified about the unprecedented nature of these outcomes: "I think this data is compelling & it should be approved... I have clearly seen some people stabilize in a way that I have never seen in any other trial."
Respiratory Function Preservation
The petition documents significant preservation of respiratory function, a critical predictor of ALS survival. Data shows a 5-8 year delay in the need for non-invasive ventilation compared to 15-month natural history, along with stabilization or improvement in Forced Vital Capacity (FVC).
Navy pilot Matt Bellina, who received NurOwn through Right to Try access, exemplifies these respiratory benefits. After receiving seven doses, Bellina stopped using non-invasive ventilation for breathing at night for more than four years, with his FVC stabilizing throughout treatment.
Biomarker Evidence and Disease Modification
NurOwn demonstrated statistically significant changes in 23 of 45 pre-specified cerebrospinal fluid biomarkers, with 15 showing p-values ≤0.001. These biomarkers provide objective evidence of target engagement across pathways of neuroprotection, neuroinflammation, and neurodegeneration.
Neurofilament light (NfL) data presented at the 2024 NEALS conference showed a 9.4% difference between NurOwn and placebo arms (p=0.037) at the end of Phase 3 trials. In EAP participants who were earlier in disease progression, those receiving the most NurOwn doses showed decreases of ≥60% in harmful NfL levels.
The petition also documents up to 85% slowing in ALS progression rates, from a trial qualification minimum loss of 1 point per month to 0.15 points per month after receiving NurOwn.
Real-World Evidence and Clinical Observations
Multiple treating neurologists have provided supporting testimony about NurOwn's clinical impact. Dr. Danielle Geraldi-Samara, a neuromuscular specialist, submitted public comments describing "striking" real-world evidence: "I have known 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."
The petition leverages real-world evidence from both the EAP and Right to Try programs, consistent with the 21st Century Cures Act. Trial participants, now unblinded, have confirmed that NurOwn halted their disease progression and helped restore function.
Multiple Approval Pathways
The Citizens' Petition argues that NurOwn meets statutory thresholds for three FDA approval pathways:
Traditional Approval: The survival data meets the "substantial evidence" threshold of one well-controlled trial plus supporting evidence, aligning with FDA recognition that survival data represents the gold standard for approvals.
Accelerated Approval: The survival data from 10 EAP participants are "reasonably likely to predict" favorable impact on mortality for the estimated 32,000 people with ALS. The petition notes this survival data surpasses that supporting accelerated approval of many cancer therapies.
Conditional Approval: NurOwn aligns with Commissioner Makary's proposed "plausible mechanism of action" threshold, with both stem cell technology and neurotrophic factors representing plausible mechanisms in ALS treatment.
Totality of Evidence Methodology
The petition advocates for FDA's use of "totality of evidence" methodology, widely accepted in oncology for evaluating therapies in heterogeneous, rare populations. Biostatistician Dr. Lee-Jen Wei of Harvard/Dana Farber analyzed multiple trial endpoints across functional domains and time points, reporting p-values of 0.045, 0.021, 0.007, and 0.005 supporting NurOwn's efficacy.
While the Phase 3 trial did not meet endpoints when including patients with most advanced ALS, it achieved statistical significance in patients earlier in disease progression, similar to cancer therapies working in stage I-II but not stage III-IV disease.
Regulatory Context and Urgency
The petition comes amid stated FDA commitments to accelerate rare disease approvals. At the 2025 Gene and Cell Therapy Forum, Secretary Kennedy indicated the FDA will "accelerate approvals for rare diseases," while Commissioner Makary and Director Prasad committed to "rapidly usher to market new products with transformational potential."
The petitioners request de novo review by the Center for Biologics Evaluation and Research (CBER), noting that the agency has not previously considered the EAP survival, respiratory, or biomarker data. They also request expedited review using the Commissioner's new Priority Voucher and propose a Phase 4 post-marketing study including biorepository and natural history database development.
The petition emphasizes the urgent need for ALS treatments, noting that the disease remains 100% fatal with no change in lethal outcomes over 86 years since Lou Gehrig's diagnosis. With ALS affecting approximately 32,000 people in the United States, the petitioners argue for the same regulatory urgency applied to terminal cancer treatments.
