Amanda Cooke

CALL TO ACTION @DrMakaryFDA @FDACBER: As a physician with #ALS, I know nothing matters more than a chance to live This #NurOwn EAP data is transformative: 90% 5-year survival vs. 10% typical. This isn't marginal; it's a PROFOUND shift. Grant accelerated approval @SecKennedy @cylebo #ALS patients, with a median survival of 2–3 years, cannot wait 5+ years for Phase 3b trial results, especially now, 15 years after NurOwn's Phase 1 trial began. The 2019 FDA ALS Guidance demands flexibility—act now to save lives. NurOwn, developed by @BrainStormCell, targets ALS’s core drivers: neuroinflammation and neurodegeneration. Its Phase 3 trial (NCT03280056) faced the same challenges plaguing ALS research—small trial sizes, patient heterogeneity, and the flawed ALS Functional Rating Scale-Revised (ALSFRS-R), a 48-point questionnaire insensitive to subtle benefits, especially in advanced patients due to its “floor effect.” Despite not meeting the ALSFRS-R endpoint, NurOwn delivered robust, statistically significant biomarker changes in cerebrospinal fluid (CSF), proving biological efficacy: Neurofilament Light (NfL): Reduced by 20% from baseline to week 20 (p<0.05), signaling slowed neurodegeneration—mirroring the NfL reductions that justified Tofersen’s accelerated approval for SOD1-ALS. Neurotrophic Factors: Increased VEGF and HGF (p<0.01), promoting neuronal survival and repair, with no changes in placebo. Neuroinflammation: Decreased MCP-1 (p<0.05), curbing a key ALS driver. Galectin-1 & LAP/TGF-β1: Enhanced neuroprotective and anti-inflammatory pathways, predictive of better outcomes. These consistent CSF changes, unaffected by ALSFRS-R’s limitations, confirm NurOwn’s plausible mechanism: stem cells deliver neurotrophic factors to protect motor neurons. In a pre-specified subgroup with less-advanced ALS, NurOwn slowed functional decline by 1.5 points on ALSFRS-R slope (p=0.08), with neurologists reporting clinical stability—improved speech, swallowing, and hand function—in some patients. Patient-reported outcomes (PROs) and real-world evidence (RWE) from expanded access programs further validate these benefits, aligning with the 2019 FDA ALS Guidance’s emphasis on PROs and RWE for rare diseases. The Tofersen precedent proves flexibility works. Despite failing its ALSFRS-R endpoint, Tofersen gained accelerated approval in 2023 based on NfL reductions, later confirmed by patient outcomes. NurOwn’s biomarker profile is equally compelling, despite sporadic ALS’s greater heterogeneity. @MartyMakary, you told @megynkelly, “For rare, incurable diseases, we may approve based on plausible mechanisms.” NurOwn meets this standard with biomarker-driven evidence of neuroprotection. @VPrasadMDMPH, your evidence-based leadership can redefine ALS’s hopeless landscape by prioritizing these data over flawed endpoints. A second Phase 3 trial, fifteen years after NurOwn’s Phase 1, is an ethical failure for a disease killing patients in 2–3 years. Peter Marks’ decision to require a Phase 3b trial overlooked that it will face the same intractable limitations—small sample sizes, heterogeneity, and ALSFRS-R’s insensitivity—dooming it to repeat past failures while patients die waiting. Tragically, some who stabilized during trials died after losing access. We propose: Invite @BrainStormCell to apply for accelerated approval, leveraging biomarkers, PROs, and RWE. Implement real-time efficacy monitoring via patient registries and digital tools (e.g., wearables tracking motor function), ensuring safety and validating outcomes post-approval. Meet ALS patients to hear firsthand accounts of NurOwn’s transformative impact—stories of hope extinguished by delays. The 2019 FDA ALS Guidance urges innovative endpoints and surrogate markers for small, heterogeneous trials. NurOwn’s data—NfL, neurotrophic factors, and PROs—meets this call. After 156 years, ALS patients deserve a chance to live. Act decisively to approve NurOwn and restore hope @realDonaldTrump @RepGuthrie @RepLarryBucshon @michaelcburgess @RepGusBilirakis @DrNealDunnFL2 @cathymcmorris @LeaderJohnThune @RepDebDingell @RepMMM @SenatorWicker @RepRobinKelly @RepBarragan @RepKimSchrier @RepLoriTrahan @BernieSanders @PattyMurray @SenBobCasey @MaryKayTurner1 @SenatorHassan @SenTinaSmith @SenMarkey @SenBillCassidy @SenMullin @lisamurkowski @RogerMarshallMD @RepJasonCrow @TeamCalvert @RepBrianFitz @ChrisCoons @RepAndyHarrisMD @DickDurbin @SenJohnThune @RepDianaDeGette @RepMikeQuigley @RepSchakowsky @rosadelauro @RandPaul @DorisMatsui @RepDonBacon o