FDA Action Update, February 2026: Complete Response Letter, Expanded Indication, and Acceptance

The FDA was busy in February 2026, making a number of decisions on potential new therapeutic agents, including issuing a complete response letter (CRL), granting an expanded approval indication, accepting a new drug application (NDA), and granting a priority review.

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.

Regenxbio's MPS II Gene Therapy RGX-121 Hit With CRL

At the start of the month, on February 9, 2026, the FDA issued a CRL to Regenxbio’s biologics license application (BLA) for clemidsogene lanparvovec (RGX-121), an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat mucopolysaccharidosis type 2 (MPS II), also known as Hunter syndrome.¹

The agency’s CRL outlined several reasons the gene therapy product was not approved, including concerns over whether the clinical trial eligibility criteria could adequately distinguish between neuronopathic and attenuated disease. Additionally, the agency questioned the comparability of the external natural history control population to the trial population, and whether the chosen surrogate endpoint could reasonably predict clinical benefit.

Notably, the CRL contained several suggested pathways to a potential approval for the product, such as a new clinical trial, carrying out dosing of additional patients with longer follow-up, and implementation of an untreated control group on-study. However, Regenxbio stated that it has concerns about the difficulty of these pathways considering the ultrarare nature of MPS II.

"This decision is devastating for the families of boys living with this progressive, life-threatening disease," Curran M. Simpson, the president and CEO of Regenxbio, said in a statement.¹ "We are concerned about FDA’s feedback regarding the overall development path and evaluation of the data in the context of the urgent need for this irreversible ultra-rare disease. We remain confident in the quality and volume of evidence demonstrating the long-term potential of RGX-121 to positively change the trajectory of Hunter syndrome. This program has been in development for over 10 years. We are incredibly grateful to all the patients, their families, investigators, and site staff who have supported this program and our continued efforts to bring a much-needed new treatment option to the Hunter syndrome community. We will continue those efforts."

FDA Accepts New Drug Application for Orexin Agonist Oveporexton in Narcolepsy Type 1, Grants Priority Review

On February 10, 2026, the FDA accepted Takeda’s NDA and granted priority review to oveporexton, investigational oral orexin receptor 2 (OX2R)–selective agonist, for the treatment of patients with narcolepsy type 1 (NT1). The agent, designed to address the underlying orexin deficiency that causes NT1 by restoring orexin signaling, has a Prescription Drug User Fee Act action date set for the third quarter of 2026.²

The NDA is supported by positive data from global phase 3 studies FirstLight (NCT06470828) and RadiantLight (NCT06505031), which showed that oveporexton, formally known as TAK-861, met all its primary and secondary end points. FirstLight and RadiantLight, 2 multicenter, placebo-controlled studies, featured 168 and 105 patients with NT1, respectively, using change in Maintenance Wakefulness Test (MWT) as the primary end point.³

“Narcolepsy type 1 is a relentless disease that can have a debilitating impact on a person’s everyday life from work and school to social interactions. The currently available treatments offer symptom relief, but don’t address the underlying cause of the disease,” Andrew Plump, MD, PhD, president of research and development at Takeda, told NeurologyLive. “Our investigational therapy oveporexton is designed to do just that by restoring orexin signaling. If approved, it would offer people living with narcolepsy type 1 and their health care providers a new approach to the way we treat this disease."

PTC Withdraws Ataluren Submission as Treatment for Nonsense Mutation Duchenne Muscular Dystrophy

After years of back and forth with the FDA, PTC Therapeutics announced that it on February 12, 2026, that it has withdrawn its NDA resubmission for ataluren, a protein restoration therapy, as a potential treatment for boys with nonsense mutation Duchenne muscular dystrophy (nmDMD). The company noted that the agency, based on what they’ve seen so far, doesn’t feel there’s enough evidence to prove the drug works well enough to approve it.⁴

Marketed as Translarna in Europe, the therapy is designed to promote ribosomal readthrough of premature stop codons in the dystrophin gene, allowing production of functional dystrophin protein in patients whose mutations create truncated, nonfunctional protein. It first gained conditional approval from the European Medicines Agency in 2014 for ambulatory patients aged 5 years and older with nmDMD.

The resubmitted NDA relied on data from the phase 3, placebo-controlled Study 041 (NCT03179631), which enrolled 359 patients with nonsense mutation DMD in the intent-to-treat population. The application also incorporated findings from the ongoing STRIDE registry, a multicenter observational study evaluating the safety and real-world effectiveness of ataluren in routine clinical practice.

“FDA shared that based on its review to date, the data in the NDA submission are unlikely to meet the agency's threshold of substantial evidence of effectiveness to support approval of Translarna. We have therefore made the decision to withdraw the NDA submission,” Matthew B. Klein, MD, chief executive officer at PTC, said in a statement.⁴ “We have worked tirelessly for over 2 decades to develop a safe and effective therapy for boys and young men affected by nonsense mutation DMD in the US and are disappointed that FDA approval cannot be achieved.”

Amgen’s mAb Inebilizumab Approved by European Commission for AChR- and MuSK-Positive Generalized Myasthenia Gravis

The European Commission (EC) has approved the monoclonal antibody (mAb) inebilizumab (Uplizna; Amgen), on February 12, 2026, as an add-on to standard therapy in the treatment of adults with generalized myasthenia gravis (gMG) in adults who are antiacetylcholine receptor (AChR) and antimuscle specific tyrosine kinase (MuSK) antibody positive.⁵

The EC’s decision was based on data from the randomized, double-blind, placebo-controlled phase 3 MINT clinical trial (NCT04524273). MINT included 238 patients with gMG who were randomly assigned 1:1 to either intravenous ineblizumab 300 mg (n = 119) or placebo (n = 119) for a 12-month period.⁶ Notably, the study met its primary end point, with a 1.9 point difference seen at Week 26 in Myasthenia Gravis Activities of Daily Living (MG-ADL) score for patients treated with inebilizumab (-4.2) versus patients treated with the placebo (-2.2) (P < .0001).⁵

Furthermore, at week 26, investigators recorded statistically significant Quantitative Myasthenia Gravis (QMG) score improvement for inebilizumab compared with placebo (inebilizumab: –4.8 overall improvement; placebo: –2.5; P = .0002).² It was also noted that inebilizumab was well-tolerated, with no new safety signals reported. The most common adverse reactions in patients treated with inebilizumab included headache and infusion-related reactions.⁷

"Uplizna offers a new approach to treating gMG by selectively targeting CD19-positive B cells, which play a key role in disease pathology," John Vissing, MD, DMSci, a professor of neurology and director of the Copenhagen Neuromuscular Center, Rigshospitalet, at the University of Copenhagen, said in a statement.⁵ "The approval provides both clinicians and patients a valuable new treatment option with the potential for long-term efficacy while addressing the challenges of long-term steroid exposure.”

FDA Expands Indication for Pitolisant to Treat Cataplexy in Pediatric Narcolepsy

On February 17, 2026, the FDA granted an expanded approval indication to Harmony Biosciences’ pitolisant (Wakix) tablets to include the treatment of cataplexy in pediatric patients aged 6 years and older with narcolepsy. With this decision, pitolisant becomes the only FDA-approved nonscheduled therapy indicated for both pediatric and adult patients with narcolepsy, regardless of the presence of cataplexy.⁸

Pitolisant's supplemental NDA for the pediatric approval in cataplexy was supported by findings from a phase 3 trial (NCT02611687), which demonstrated significant reductions in EDS and cataplexy in pediatric patients aged 6 to 17 years with narcolepsy treated with 5 mg to 40 mg a day of the therapy. Published in Lancet Neurology, these findings suggested that pitolisant is a safe and effective treatment for children and adolescents with narcolepsy.⁹

“Given that narcolepsy often onsets in children and young adults, having more FDA-approved treatment options for this younger population is absolutely critical. Finding a good treatment regimen that works well for each child and teen allows them their greatest chance at getting through school and pursuing their dreams,” narcolepsy patient advocate Julie Flygare, JD, the president and CEO at Project Sleep, told NeurologyLive.

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REFERENCES
1. Regenxbio announces regulatory update on RGX-121 BLA for MPS II. News release. Regenxbio. February 9, 2026. Accessed March 5, 2026. https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-presents-positive-twelve-month-pivotal-data-phase
2. U.S. Food and Drug Administration accepts new drug application and grants priority review for Takeda’s oveporexton (TAK-861) as a potential first-in-class therapy for narcolepsy type 1. News release. Takeda. March 5, 2026. Accessed February 11, 2026. https://www.takeda.com/newsroom/newsreleases/2026/fda-accepts-nda-priority-review-oveporexton-narcolepsy-type-1/
3. Takeda announces positive results from two pivotal phase 3 studies of oveporexton (TAK-861) in narcolepsy type 1. News release. Takeda. July 14, 2025. Accessed March 5, 2026. https://www.takeda.com/newsroom/newsreleases/2025/positive-results-phase-3-oveporexton-narcolepsy-type-1/
4. PTC Therapeutics provides regulatory update on Translarna. News release. PTC Therapeutics. February 12, 2026. Accessed March 5, 2026. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-provides-regulatory-update-translarnatm-2
5. European Commission approves Amgen's Uplizna® for generalized myasthenia gravis. News release. Amgen. February 12, 2026. Accessed March 5, 2026. https://www.amgen.com/newsroom/press-releases/2026/02/european-commission-approves-amgens-uplizna-for-generalized-myasthenia-gravis
6. Amgen Conference Call to Discuss New Topline Data in Inflammation and Rare Disease. News release. Amgen. September 24, 2024. Accessed March 5, 2026. https://amgen2.rev.vbrick.com/#/videos/750c4b9d-5c91-4634-8906-a16b53f346bf.
7. FDA Approves UPLIZNA® For Adults With Generalized Myasthenia Gravis. News release. Amgen. December 11, 2025. Accessed March 5, 2026. https://investors.amgen.com/news-releases/news-release-details/fda-approves-upliznar-adults-generalized-myasthenia-gravis
8. Harmony Biosciences Receives U.S. Food and Drug Administration Approval for WAKIX® (pitolisant) for the Treatment of Cataplexy in Pediatric Narcolepsy. News release. Harmony Biosciences. February 17, 2026. AccessedMarch 5, 2026..https://ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-receives-us-food-and-drug-administration-1
9. Dauvilliers Y, Lecendreux M, Lammers GJ, et al. Safety and efficacy of pitolisant in children aged 6 years or older with narcolepsy with or without cataplexy: a double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2023;22(4):303-311. doi:10.1016/S1474-4422(23)00036-4