FDA Action Update, December 2025: Acceptance, Approval, and Clearance

The FDA was busy in December 2025, making a number of decisions on potential new therapeutic agents, including accepting a new drug application, clearing the initiation of a clinical trial, granting an approval, pushing back a review, and expanding an indication.

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 into 1 place. The coverage includes the latest FDA approvals, new designations, submissions, resubmissions, and clinical trial initiations and holds.

FDA Accepts NDA for Low-Sodium Oxybate TRN-257 in Narcolepsy and Idiopathic Hypersomnia

At the beginning of the month, on December 9, 2025, the FDA accepted Tris Pharma’s new drug application (NDA) for TRN-257 for the treatment of cataplexy or excessive daytime sleepiness in adults with narcolepsy, as well as excessive daytime sleepiness in adults with idiopathic hypersomnia, with a PDUFA date set for June 20, 2026.¹ The agent incorporates 2 of the company’s proprietary technology platforms, RaftWorks and LiquiXR, to achieve a controlled-release profile and support a once-nightly, low-sodium dosing regimen.

The NDA submission is supported by data from multiple pharmacokinetic and safety studies and incorporates Model-Informed Drug Development-based approaches to showcase the efficacy and safety of TRN-257. According to Tris Pharma, the submission also references the agency's prior safety and efficacy findings for currently marketed oxybate products. In addition, it includes a comprehensive Human Factors Engineering and Usability Engineering study report, which demonstrated that representative patients were generally able to perform tasks and use TRN-257 as intended when following the proposed labeling.

"Currently, patients face a difficult trade-off with existing treatments that either burden them with high sodium levels, posing significant cardiovascular risks, or require disruptive twice-nightly dosing that interrupts sleep, that otherwise is intended to induce sleep," Maurice M. Ohayon, MD, DSc, PhD, professor and director of the Stanford Sleep Epidemiology Research Center at Stanford University, said in a statement.¹ "As the first oxybate formulation to combine a convenient once-nightly regimen with the lowest sodium content, TRN-257 is uniquely designed to eliminate this compromise."

FDA Clears Pivotal Phase 3 PREVAiLS Study of Pridopidine in Early, Rapidly Progressive ALS

A couple of days later, on December 11, 2025, the FDA cleared the initiation of a pivotal, 500-patient, randomized, placebo-controlled phase 3 trial dubbed PREVAiLS, which will assess the efficacy and safety of pridopidine (Prilenia Therapeutics/Ferrer) in patients with early-stage, rapidly progressive amyotrophic lateral sclerosis (ALS). The company noted that recruitment at the first clinical trial sites in the United States is planned to begin in early 2026, with international sites expected to follow pending regulatory approval.²

PREVAiLS will enroll adults diagnosed with definite or probable ALS who are within 18 months of symptom onset across up to 60 ALS treatment centers worldwide. The trial design consists of a 48-week double-blind, placebo-controlled phase, randomized 3:2 to receive either pridopidine or placebo, followed by a 48-week open-label extension. The primary end point is change from baseline in the ALS Functional Rating Scale–Revised (ALSFRS-R), adjusted for mortality, at 48 weeks while secondary and exploratory end points include measures of speech, respiratory and bulbar function, quality of life, survival, patient-reported outcomes, and plasma biomarkers.

“This study has the clear aim of evaluating the efficacy and safety of a much-needed new treatment option for ALS,” PREVAiLS steering committee member and investigator Sabrina Paganoni, MD, PhD, co-director of Massachusetts General Hospital Neurological Clinical Research Institute, said in a statement.² “Early detection and management are essential for preserving function, with slowing of functional decline, maintaining speech and prolonging survival being ALS therapeutic priorities. This makes pridopidine’s S1R activation mechanism of particular interest, holding promise in ALS by enhancing key cellular mechanisms and promoting neuroprotection."

FDA Approves Inebilizumab for AChR- and MuSK-Positive Generalized Myasthenia Gravis

On the same day, on December 11, 2025, the FDA approved inebilizumab (Uplizna; Amgen) for the treatment of generalized myasthenia gravis (gMG) in adults who are antiacetylcholine receptor (AChR) and antimuscle specific tyrosine kinase (MuSK) antibody positive. This marks the third FDA-approved indication for inebilizumab, following approvals in antiaquaporin-4 antibody positive neuromyelitis optica spectrum disorder and immunoglobulin G4–related disease.³

The approval of inebilizumab for gMG is supported by data from the phase 3 MINT trial (NCT04524273). In the trial, 238 patients with gMG were randomly assigned 1:1 to either intravenous ineblizumab 300 mg (n = 119) or placebo (n = 119) for a 12-month period. Change from baseline in Myasthenia Gravis Activities of Daily Living (MD-ADL), the study’s primary end point, was statistically significant for inebilizumab-treated patients, with scores of –4.2 compared with –2.2 for those on placebo (P <.0001). The therapy showed a safe and well tolerated profile, consistent with prior safety findings.

"This approval is a truly meaningful milestone – personally, as the global principal investigator for MINT, and most importantly, for the many patients who will benefit. I’m thrilled to see a new FDA-approved option for patients living with this rare and debilitating disease, and for the clinicians who care for them," global principal investigator Richard J. Nowak, MD, MS, director of the Myasthenia Gravis Clinic and associate professor of neurology at Yale School of Medicine, told NeurologyLive^®. "This approval represents significant progress for the gMG community and adds an important new option to the clinical toolbox."

Tolebrutinib Falls Short in Phase 3 PERSEUS Study, Forcing Decision to Redact Regulatory Submission

A few days later, on December 15, 2025, Sanofi’s tolebrutinib, an investigational Bruton’s tyrosine kinase (BTK) inhibitor, did not meet its end points in the phase 3 PERSEUS study (NCT04458051) of patients with primary progressive multiple sclerosis (PPMS), and a regulatory submission is therefore not expected. In addition, it’s been reported that the FDA has pushed back its review of the agent as a treatment for nonrelapsing secondary progressive MS (nrSPMS).⁴

More detailed results from the global, double-blind, randomized trial are expected to be presented at an upcoming meeting. In the release, it was noted that tolebrutinib did not meet its primary end point of delaying time of onset of 6-month composite confirmed disability progression (CDP) compared with placebo in the study cohort, which included those aged 18-55 with an Expanded Disability Status Scale (EDSS) of between 2.0 and 6.5.

"We are disappointed by today’s results; however, we do believe that these results will improve our understanding of the underlying disease biology of multiple sclerosis," Houman Ashrafian, executive vice president and head of Research & Development at Sanofi, said in a statement.⁴ "We extend our deepest appreciation to the study participants, their families, and healthcare professionals who support our scientific and innovative vision. Our commitment to the multiple sclerosis community remains unchanged, as do our efforts to pursue novel advancements that address existing unmet needs and we remain confident in the value tolebrutinib can bring to those living with non-relapsing secondary progressive multiple sclerosis."

FDA Expands Indication for n‐Butyl Cyanoacrylate in Chronic Subdural Hematoma

A few days later, on December 18, 2025, the FDA approved the expanded indication for Johnson & Johnson's n‐butyl cyanoacrylate (Trufill) liquid embolic system as an adjunct to surgery for middle meningeal artery (MMA) embolization in patients with symptomatic subacute and chronic subdural hematoma (cSDH). The company noted that therapy has been used in neurovascular embolization for more than 25 years and has supported the treatment of arteriovenous malformations since its initial FDA approval in 2000.⁵

The approval was supported by findings from the MEMBRANE randomized controlled trial (NCT04816591), which evaluated the safety and efficacy of MMA embolization in approximately 376 adult patients with cSDH. In trial, researchers observed a statistically significant treatment benefit with n-butyl cyanoacrylate compared with standard of care in patients treated with or without surgery (P = .044).² Overall, the study demonstrated superior efficacy of n-butyl cyanoacrylate and supported its safety in the treatment of cSDH.

“The MEMBRANE trial provides high-quality evidence that treating the subdural membrane itself with MMA embolization with Trufill nBCA as an adjunct to surgery prevents recurrence in patients with chronic subdural hematomas," investigator Chris Kellner, MD, the director of Cerebrovascular & Intercerebral Hemorrhage programs at Mount Sinai told NeurologyLive^®. " We are proud at Mount Sinai to have led the clinical trial and to partner with J&J in the future to train neurointerventionists and educate the community about this new treatment."

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REFERENCES
1. Tris Pharma Announces FDA Acceptance of NDA for Once-Nightly, Low-Sodium Oxybate Product for Narcolepsy and Idiopathic Hypersomnia. News release. Tris Pharma. December 9, 2025. Accessed January 2, 2026. https://www.trispharma.com/tris-pharma-announces-fda-acceptance-nda-oxybate-narcolepsy/
2. Prilenia and Ferrer Announce FDA Clearance to Start the “PREVAiLS” Pivotal Phase 3 Study with Pridopidine in ALS. News release. Prilenia Therapeutics. December 11, 2025. Accessed January 2, 2026. https://news.prilenia.com/press-releases/press-release-details/2025/Prilenia-and-Ferrer-Announce-FDA-Clearance-to-Start-the-PREVAiLS-Pivotal-Phase-3-Study-with-Pridopidine-in-ALS/default.aspx
3. FDA Approves UPLIZNA^® For Adults With Generalized Myasthenia Gravis. News release. Amgen. December 11, 2025. Accessed January 2, 2026. https://investors.amgen.com/news-releases/news-release-details/fda-approves-upliznar-adults-generalized-myasthenia-gravis
4. Sanofi provides update on tolebrutinib in primary progressive multiple sclerosis. Sanofi. News release. December 15, 2025. Accessed January 2, 2026. https://www.sanofi.com/assets/dotcom/pressreleases/2025/2025-12-15-06-05-00-3205094-en.pdf
5. Johnson & Johnson Receives FDA Approval for TRUFILL n‑BCA Liquid Embolic System for the Treatment of Symptomatic Chronic Subdural Hematoma. News release. Johnson & Johnson. December 18, 2025. Accessed January 2, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-receives-fda-approval-for-trufill-n-bca-liquid-embolic-system-for-the-treatment-of-symptomatic-chronic-subdural-hematoma