FDA Action Update, March 2026: Lift on CRL, Expanded Approvals, and Priority Review

The FDA was busy in March 2026, making a number of decisions on potential new therapeutic agents, including lifting a complete response letter, accepting a new drug application for priority review, and granting expanded approvals.

With all the treatments that have progressed through the pipeline of clinical development, the NeurologyLive^® team has been hard at work covering all the agency movements to make sure you are up to date on the latest news in neurology. To give you a chance to catch up on any of the headlines you may have missed in December, we’ve compiled all the updates here. The coverage includes the latest FDA approvals, new designations, submissions, resubmissions, and clinical trial initiations and holds.

Capricor’s DMD Cardiomyopathy Cell Therapy Deramiocel Back Under Review by FDA

At the beginning of the month, on March 10, 2026, the FDA lifted the complete response letter (CRL) that it previously issued to Capricor Therapeutics’ biologics license application (BLA) for deramiocel, an investigational allogeneic cardiosphere-derived cell therapy intended for the treatment of Duchenne muscular dystrophy (DMD) cardiomyopathy.¹

The BLA is now considered a Class 2 resubmission. The new Prescription Drug User Fee Act (PDUFA) action date has been set at August 22, 2026. The FDA made the decision to continue its review of the BLA in response to newly submitted data and supporting documentation from the ongoing phase 3 HOPE-3 clinical trial (NCT05126758). Data from HOPE-3 had not been part of the original rolling BLA submission, which was completed in Janaury 2025 and supported by data from the HOPE-2 clinical trial (NCT03406780) and HOPE-2’s open-label extension (OLE) study (HOPE-2-OLE; NCT04428476), results from which were compared to an FDA funded natural history dataset.

“We submitted our documentation in response to the CRL that we got from FDA last summer,” Linda Marbán, PhD, the chief executive officer of Capricor, told NeurologyLive. “They wanted a randomized, double-blind, placebo-controlled trial to look specifically at the cardiomyopathy associated with Duchenne, which is what our BLA was for. We were able to give them that in the HOPE-3 clinical data. We had asked them to switch the primary efficacy end point to ejection fraction (EF), a measure of how the heart meets the needs of the body. Because the open BLA was for cardiomyopathy, they didn't want to switch the primary efficacy end point and so they said to submit the data as it is.”

FDA Approves Leucovorin for Cerebral Folate Transport Deficiency

On the same day, March 10, 2026, the FDA approved expanded use of leucovorin calcium tablets (Wellcovorin) for the treatment of adult and pediatric patients with cerebral folate transport deficiency associated with confirmed variants in the folate receptor 1 (FOLR1) gene. The regulatory decision marks the first FDA-approved therapy specifically indicated for this rare genetic neurological condition.²

The approval was supported by a systematic review of published literature that included case reports with patient-level data as well as mechanistic evidence supporting the biological rationale for leucovorin therapy. The FDA worked with GlaxoSmithKline, the new drug application holder for Wellcovorin, to update the drug’s labeling to include information supporting safe and effective use in patients with FOLR1-related cerebral folate transport deficiency. The approval was issued through a supplemental new drug application (NDA) for the existing product.

“Today’s approval represents a significant milestone for patients living with cerebral folate transport deficiency due to the FOLR1 variant, a rare genetic condition that has had no FDA-approved treatment options until today,” Marty Makary, MD, MPH, commissioner of the FDA, said in a statement.² “This action may benefit some individuals with FOLR1-related cerebral folate transport deficiency who have developmental delays with autistic features.”

FDA Accepts Zilganersen New Drug Application for Priority Review in Alexander Disease

Later on in the month, on March 23, 2026, the FDA accepted for priority review Ionis Pharmaceuticals’ NDA for its investigational RNA-targeted therapy zilganersen as a potential treatment of patients with Alexander disease (AxD), a rare neurologic disorder. The agency has assigned a prescription drug user fee act (PDUFA) target action date of September 22, 2026.³

The NDA and priority review designation were supported by results from a pivotal phase 1-3 study (NCT04849741) evaluating zilganersen in children and adults living with AxD, in which the therapy met its primary end point of gait stabilization. Topline data indicated that zilganersen 50 mg demonstrated a statistically significant 33.3% mean difference in gait speed on the 10-Meter Walk Test compared with control at 61 weeks (P = .0412). The company reported that the treatment was generally well tolerated, with most adverse events (AEs) classified as mild or moderate in severity.

“We are pleased the FDA has granted Priority Review for zilganersen. This decision recognizes the urgent need for treatment options and brings us one step closer to offering patients, who currently have no disease-modifying therapies, a potential treatment as quickly as possible,” an Ionis spokesperson told NeurologyLive. “If approved, zilganersen will be the first and only treatment for Alexander disease, marking a breakthrough for patients who are living with this rare, often fatal neurological condition.”

FDA Grants Accelerated Approval to Tividenofusp Alfa for Neurologic Hunter Syndrome

A few days later, on March 25, 2026, the FDA granted accelerated approval to tividenofusp alfa-eknm (Denali Therapeutics) for the treatment of neurologic manifestations of Hunter syndrome, also known as mucopolysaccharidosis type II (MPS II), in pediatric patients. Marketed as Avlayah, it becomes the first therapy specifically engineered to cross the blood-brain barrier in this rare lysosomal storage disorder.⁴

The FDA’s accelerated approval of tividenofusp alfa was supported by data from an ongoing phase 1/2, open-label study of 47 patients with Hunter syndrome, with findings that have matured over time. Previously reported data demonstrated substantial reductions in both central nervous system and peripheral disease biomarkers.

“The approval of AVLAYAH is a new era for the Hunter syndrome community as we deliver the first FDA-approved therapy designed to cross the brain’s protective barrier for individuals and families living with this debilitating disease,” Ryan Watts, PhD, co-founder and chief executive officer at Denali, said in a statement.⁴ “This approval reflects the determination and partnership of the MPS community, as well as the FDA’s collaborative engagement to incorporate biomarker evidence to help accelerate the development of urgently needed treatments.”

FDA Approves Higher Strength, More Effective Nusinersen Dose for Spinal Muscular Atrophy

At the end of the month, on March 30, 2026, the FDA approved a new higher dose strength for nusinersen (Spinraza; Biogen) as a treatment for patients with spinal muscular atrophy (SMA). This new dosing regimen, which is comprised of 50 mg/5 mL and 28 mg/5 mL doses, is designed to deliver a higher concentration of drug through both the loading and maintenance dosing phases, leading to more efficacious results for patients with the disease.⁵

The high-dose regimen of nusinersen, expected to become available in the coming weeks, introduces a faster loading schedule for treatment-naïve patients. This approach includes two 50 mg doses given 14 days apart, followed by ongoing maintenance injections of 28 mg every four months. For patients switching from the low-dose regimen, treatment would continue on the same four-month dosing interval after completing a single high-dose loading phase.

“I think it’s incredibly exciting,” Crystal Proud, MD, a study author on DEVOTE, told NeurologyLive regarding the approval. “We’re nearing 10 years of approval of Spinraza later this year, and our patients have had incredible success over that time period. It’s natural to then say, well, what’s next? Where can we do better?”

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REFERENCES
1. Capricor Therapeutics announces establishment of new PDUFA date for Deramiocel BLA. News release. Capricor Therapeutics. March 10, 2026. Accessed March 31, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/338/capricor-therapeutics-announces-establishment-of-new-pdufa
2. FDA approves first treatment for patients with cerebral folate transport deficiency. U.S. Food and Drug Administration. News Release. March 10, 2026. Accessed March 31, 2026.https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-cerebral-folate-transport-deficiency
3. Ionis announces zilganersen New Drug Application for Alexander disease (AxD) accepted by FDA for Priority Review. News release. Ionis Pharmaceuticals. March 23, 2026. Accessed March 31, 2026. https://ir.ionis.com/news-releases/news-release-details/ionis-announces-zilganersen-new-drug-application-alexander
4. Denali Therapeutics Announces U.S. FDA Approval of AVLAYAH™ (tividenofusp alfa-eknm) for Treatment of Hunter Syndrome (MPS II). News release. Denali Therapeutics. March 25, 2026. Accessed March 31, 2026. https://investors.denalitherapeutics.com/news-releases/news-release-details/denali-therapeutics-announces-us-fda-approval-avlayahtm
5. FDA Approves New High Dose Regimen of SPINRAZA® (nusinersen) for Spinal Muscular Atrophy. News release. Biogen. March 30, 2026. Accessed March 31, 2026. https://investors.biogen.com/news-releases/news-release-details/fda-approves-new-high-dose-regimen-spinrazar-nusinersen-spinal