FDA Action Update, February 2025: Approvals, Designations, and Acceptances

The FDA was busy in February 2025, making a number of decisions on potential new therapeutic agents including granting approvals, acceptances, and designations.

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 over the course of the last month, we’ve compiled all the updates into one place. The coverage includes the latest FDA approvals, new designations, submissions and resubmissions, and clinical trial initiations and holds.

Click the read more buttons for more details and information about each update.

FDA Approves Apomorphine Infusion Device SPN-830 as New Parkinson Treatment

Early in the month, on February 4, the FDA approved Supernus Pharmaceuticals’ investigational agent SPN-830 (Onapgo) as the first and only subcutaneous apomorphine infusion device for the treatment of motor fluctuations in adults with advanced Parkinson disease (PD). The company also noted that it will make SPN-830 available in the second quarter of 2025 with a support team of experts, including a robust nurse education program, and access support at launch.¹

The therapy’s approval was based on data from the TOLEDO study (NCT02006121), a randomized, double-blind study in which treatment with the device was associated with a difference of –1.89 hours per day of OFF time for patients with PD in comparison with placebo. Published in the Lancet Neurology in 2018, the study randomly assigned 106 patients living with the disease to either 3-mg/hour to 8-mg/hour dose of apomorphine (n = 53) or placebo saline infusion (n = 53) during their wake hours for a 12-week period.²

“The approval of a new device that delivers a drug for folks with Parkinson’s disease, using an under the skin technology, and not requiring a wire in the brain or a tube in the stomach, is a huge advantage for many folks looking to improve their Parkinson’s disease symptoms," Michael S. Okun, MD, the national medical adviser for the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases, told NeurologyLive in a recent interview. “This therapy has been under development for many years and finally got over the hurdle for FDA approval. We know from studies that have been published in journals like the Lancet Neurology that the number of hours of ‘good quality on medication time’ for folks with Parkinson will potentially increase about two hours. This is a meaningful change.”

FDA Approves Mirdametinib for NF1-Associated Plexiform Neurofibromas in Adults and Children

About a week later, on February 11, the FDA granted approval to mirdametinib (Gomekli; SpringWorks Therapeutics) for the treatment of adult and pediatric patients aged 2 years and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) that are not amenable to complete surgical resection.³

The approval was based on data from the phase 2 ReNeu trial (NCT03962543), in which mirdametinib demonstrated an overall response rate (ORR) of 41% (95% CI, 29-55) in adult patients (n = 58) and 52% (95% CI, 38-65) in pediatric patients (n = 56). The treatment, which is a highly selective MEK inhibitor, offers a new option for patients with NF1 with inoperable PN, marking a significant advancement, particularly for adults who have lacked an FDA-approved therapy.

“This approval is significant because mirdametinib provides a much-needed option for both adults and children with NF1 who have symptomatic plexiform neurofibromas that are not candidates for surgery and that severely impact quality of life,” Christopher L. Moertel, MD, of the University of Minnesota and principal investigator of the ReNeu trial, told NeurologyLive's sister site, OncLive. “For adults with NF1, this represents a major step forward.”

FDA Accepts NDA Application for Troriluzole as Potential First Treatment for Spinocerebellar Ataxia

On the same day, on February 11, the FDA accepted Biohaven’s new drug application (NDA) for its investigational agent troriluzole, a third-generation prodrug that modulates glutamate, for the treatment of patients with spinocerebellar ataxia (SCA). The agency is expected to have a decision sometime in Q3 of this year and if approved, troriluzole would become the first marketed treatment specific to SCA.⁴

Troriluzole’s submission comprised data from the pivotal Study BHV4157-206-RWE (NCT06529146) along with confirmatory and supportive data from studies BHV4157-201 and BHV4157-206 (NCT03701399). Study BHV4157-206-RWE, which met its primary end point, comprised of multiple sources of real-world data, including the Clinical Research Conosrtium for the Study of Cerebellar Ataxia cohort (CRC-SCA), the European Integrated Project on Spinocerebellar Ataxias cohort (EUROSCA), and the 3-year open-label extension (OLE) data from troriluzole-treated patients from the previously completed Study BHV4157-206.

"Our NDA filing is the culmination of over 8 years of clinical research and represents an important collaboration across the SCA community,” Melissa Beiner, MD, SCA Clinical Development Lead, Biohaven, said in a statement.⁴ “The FDA decision to grant Priority Review demonstrates the extremely high unmet need in this rare neurodegenerative disease. Time is of the essence for patients with SCA, who are suffering relentless and irreversible functional decline including impairments in coordination and balance leading to falls, loss of ambulation, and difficulties with vision, speech and swallowing."

FDA Fast Tracks Innovative Cell Therapy Troculeucel for Alzheimer Disease

A day later, on February 12, the FDA granted fast track designation to NKGen Biotech’s troculeucel, a novel cell-based, patient specific ex vivo expanded autologous natural killer (NK) cell, immunotherapeutic candidate as a potential treatment for Alzheimer disease (AD). The company is currently enrolling patients with moderate AD for its phase 2a trial, with updated clinical data expected by the end of 2025.⁵

Also known as SNK01, the novel NK cell manufacturing technology enables large-scale ex vivo production and expansion of NK cells. Expanded NK cells are an autologous biological product using the patient’s own cells that are cultivated and expanded outside the body and then reinfused into the same patient. The NK cell expansion process produces activated, fully functional non-genetically modified NK cells with both immunoregulatory and cytotoxic potential.

"We are pleased with the FDA’s decision to grant Fast Track designation for troculeucel. This decision underscores the significant unmet need for effective treatments for patients with moderate AD. We specifically targeted the moderate stage population as they represent about 30% of all Alzheimer cases and most, if not all, of the current focus has been on early/mild patients," Paul Y. Song, MD, chairman and chief executive officer at NKGen, said in a statement.⁵

FDA Grants Fast Track Designation to Promising Multiple System Atrophy Agent Amlenetug

On the same day, February 12, the FDA gave fast track designation to Lundbeck’s investigational agent, amlenetug, as a potential treatment for multiple system atrophy (MSA), a disabling movement disorder with no therapies currently approved. Formerly known as Lu AF82422, the anti-alpha-synuclein (α-syn) antibody is currently being evaluated in a phase 3 trial dubbed MASCOT (NCT06706622).⁶

Prior to MASCOT, the therapy first showed its promise in the phase 2 AMULET trial (NCT05104476), a randomized, double-blind, placebo-controlled study of 61 patients with MSA. While it did not meet its primary end point of statistically slowing disease progression against placebo, the signal of efficacy was more pronounced in a less impaired population of those with the disease, further supporting the therapy’s development in larger populations.

"We are pleased that amlenetug has received Fast Track Designation for the potential treatment of Multiple System Atrophy," Johan Luthman, executive vice president and head of Research & Development at Lundbeck, said in a statement.⁶ "This is a step forward in our commitment to address significant unmet needs in this devastating disease."

FDA Approves Tablet Formulation of Risdiplam for Spinal Muscular Atrophy

On the same day, on February 12, the FDA approved a new tablet formulation for risdiplam (Evrysdi; Genentech), one of the few authorized therapies to treat patients with spinal muscular atrophy (SMA), according to a company announcement. With the approval, it becomes the first and only tablet available to this patient population, who often face challenges with digesting and taking medication.⁷

The new tablet, which comes in a 5-mg dose to be swallowed whole or dispersed in water, is expected to be available in the coming weeks. Similar to its existing prescribing information, the tablet is applicable for those with the disease aged 2 years or older who weigh more than 44 lbs. Risdiplam, a survival motor neuron 2 (SMN2) pre-mRNA splicing modifier, was originally approved in 2020 as a liquid oral solution, becoming the second approved agent for SMA.

"Evrysdi has robust potential to modify the SMA disease trajectory and has already been used to treat thousands of patients to date. This approval marks another significant step forward," Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in a statement.⁷ "The Evrysdi tablet combines established efficacy with convenience, providing an additional flexible option for SMA management."

FDA Refuses to File Harmony’s Supplemental NDA of Pitolisant in Idiopathic Hypersomnia

A few days later, on February 19, the FDA gave a refusal to file (RTF) letter to Harmony Biosciences for its supplemental new drug application (NDA) of pitolisant, a selective histamine 3 receptor antagonist/inverse agonist, for the treatment of excessive daytime sleepiness (EDS) among adult patients with idiopathic hypersomnia (IH). Additionally, the company noted that it is on track to initiate a phase 3 registrational trial of a higher-dose formulation of pitolisant for IH in the fourth quarter of 2025, with a target PDUFA date in 2028.⁸

In October 2023, topline data reported from the phase 3 INTUNE study (NCT05156047) assessing pitolisant in patients with IH showed no statistically significant difference between the therapy and placebo in the primary end point of improving EDS. Despite these results, results revealed that the treatment reached statistical significance in additional prespecified end points including disease severity and functional status.⁹

“We were disappointed with the decision not to review our submission, especially given its potential benefit to patients with idiopathic hypersomnia, a rare disease where the only approved treatment option is a schedule 3, triple attestation REMS product and where the off-label use of stimulants is widely prevalent," Kumar Budur, MD, MS, chief medical and scientific officer at Harmony Biosciences, told NeurologyLive in a recent interview. "The IH community recently engaged FDA in an Externally Led Patient Focused Drug Development Meeting (EL-PFDD) where the burden of the disease and the need for new, non-scheduled treatment options were the prevailing themes. In addition, the Hypersomnia Foundation and more than 650 members of the community signed a petition requesting FDA review of the file."

FDA Accepts NDA for Vatiquinone as Potential Treatment for Friedreich Ataxia

On the same day, February 19, the FDA accepted PTC Therapeutics’ new drug application (NDA) for its investigational agent vatiquinone as a treatment for patients with Friedreich ataxia (FA), a rare, inherited neurodegenerative disorder that primarily affects the nervous system and heart. The agency has assigned a prescription drug user fee act (PDUFA) target date of August 19, 2025, for the first-in-class selective inhibitor of 15-Lipoxygenase (15-LO).¹⁰

The NDA for the small molecule therapy was based on findings from the pivotal MOVE-FA study (NCT04577352) as well as 2 long-term trials that featured pediatric and adult patients with FA. MOVE-FA, a registration-directed trial, did not meet its primary end point of change in overall modified Friedreich Ataxia Rating Scale (mFARS; P = .14); however, there was a statistically significant effect (P = .021) observed on the mFARS upright stability subscale, a pre-specified end point. In the study’s open-label extension, treatment with vatiquinone resulted in a 3.7-point benefit (P <.0001; n = 70) in mFARS at 144 weeks relative to a matched natural history cohort from the Friedreich Ataxia Clinical Outcome Measures disease registry.

"We are excited to be one step closer to bringing an approved therapy to all patients with Friedreich's ataxia," Matthew B. Klein, MD, chief executive officer at PTC, said in a statement.¹⁰ "If approved, vatiquinone would be the first therapy for pediatric patients with FA, and provide a potential safe, well-tolerated and effective treatment alternative for adults. The granting of priority review by FDA reflects the significant unmet need for younger patients with FA. We look forward to working collaboratively with FDA during the review process."

FDA Removes Clinical Hold on Duchenne Muscular Dystrophy Agent ENTR-601-44

About a few day later, on February 24, the FDA lifted its clinical hold on Entrada Therapeutics’ investigational new drug (IND) application for ENTR-601-44 in Duchenne muscular dystrophy (DMD) and provided authorization to initiate ELEVATE-44-102, a randomized, double-blind placebo-controlled, multiple ascending dose (MAD) phase 1b study assessing the investigational therapy in adult patients with a confirmed mutation in the DMD gene amenable to exon 44 skipping.¹¹

The phase 1b trial is investigating the safety and tolerability of ENTR-601-44 in approximately 32 nonambulatory and ambulatory adult patients with DMD who are exon 44 skipping amenable. Entrada noted that MAD study is also designed to assess target engagement as measured by exon skipping and dystrophin production, and pharmacokinetics. Dosing for the trial will be administered every 6 weeks, with the planned doses across 4 cohorts anticipated to range from 0.16 mg/kg up to 1.28 mg/kg.

"Today we announced that we’ve received authorization from the U.S. FDA to initiate ELEVATE-44-102, a Phase 1b MAD clinical study of ENTR-601-44 in adults living with Duchenne muscular dystrophy who are amenable to exon 44 skipping," Dipal Doshi, CEO at Entrada Therapeutics, told NeurologyLive in a recent interview. "Nearly half of people living with Duchenne who are amenable to exon 44 skipping are adults, yet they are unfortunately often left out of clinical studies due to the advanced stage of their disease. We’re pleased to make the ENTR-601-44 study available to both non-ambulatory and ambulatory adult patients, which will also provide clinical experience from this important population."

FDA Approves Medtronic’s Adaptive Deep Brain Stimulation for Parkinson Disease

On the same day, February 24, the FDA granted approval to Medtronic’s Adaptive deep brain stimulation (aDBS) and BrainSense Electrode Identifier (EI), marking a significant advancement in personalized care for patients with Parkinson disease (PD).¹²

The decision comes less than 2 months after the European Union gave CE Mark approval for the pair of digital modalities to be used in PD care. Each technology is a bit different: aDBS dynamically adjusts DBS in real-time based on patient-specific brain activity whereas the EI optimizes initial DBS programming by precisely identifying the strongest signal location. Research has shown that through EI, clinicians can conduct more accurate and precise initial programming that is 85% faster than traditional electrode selection.

"This new era in Parkinson's care represents more than a decade of intentional innovation—ushering in personalized neuromodulation at scale that responds to a patient's changing needs, equipping clinicians with unparalleled insights, and setting a new standard for DBS therapy," Brett Wall, executive vice president and president of the Medtronic Neuroscience Portfolio, said in a statement.¹²

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REFERENCES
1. Supernus Announces FDA Approval of ONAPGO™ (apomorphine hydrochloride) for Parkinson’s Disease. News Release. Supernus. Published February 4, 2025. Accessed February 4, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-fda-approval-onapgotm-apomorphine
2. Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomized, placebo-controlled trial. Lancet Neurol. 2018;17(9):749-759. doi:10.1016/S1474-4422(18)30239-4
3. FDA approves mirdametinib for adult and pediatric patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas not amenable to complete resection. FDA. February 11, 2025. Accessed February 11, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirdametinib-adult-and-pediatric-patients-neurofibromatosis-type-1-who-have-symptomatic
4. Biohaven Announces FDA Acceptance and Priority Review of Troriluzole New Drug Application for the Treatment of Spinocerebellar Ataxia. News release. Biohaven. February 11, 2025. Accessed February 11, 2025. https://www.prnewswire.com/news-releases/biohaven-announces-fda-acceptance-and-priority-review-of-troriluzole-new-drug-application-for-the-treatment-of-spinocerebellar-ataxia-302373056.html
5. NKGen Biotech Receives U.S. FDA Fast Track Designation for Troculeucel for the Treatment of Moderate Alzheimer’s Disease. News release. NKGen Biotech. February 12, 2025. Accessed February 13, 2025. https://www.globenewswire.com/news-release/2025/02/12/3024994/0/en/NKGen-Biotech-Receives-U-S-FDA-Fast-Track-Designation-for-Troculeucel-for-the-Treatment-of-Moderate-Alzheimer-s-Disease.html
6. Lundbeck's potential treatment amlenetug for Multiple System Atrophy receives Fast Track Designation from the FDA. News release. Lundbeck. February 12, 2025. Accessed February 12, 2025. https://www.prnewswire.com/news-releases/lundbecks-potential-treatment-amlenetug-for-multiple-system-atrophy-receives-fast-track-designation-from-the-fda-302374577.html
7. FDA Approves Genentech’s Evrysdi Tablet as First and Only Tablet for Spinal Muscular Atrophy (SMA). News release. Genentech. February 12, 2025. Accessed February 12, 2025. https://www.businesswire.com/news/home/20250210728175/en/FDA-Approves-Genentech%E2%80%99s-Evrysdi-Tablet-as-First-and-Only-Tablet-for-Spinal-Muscular-Atrophy-SMA
8. Harmony Biosciences Provides Update on the Status of the Supplemental New Drug Application for Pitolisant in Idiopathic Hypersomnia. News Release. Harmony Biosciences. Published February 19, 2025. Accessed February 19, 2025. https://ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-provides-update-status-supplemental-new-drug
9. Harmony Biosciences Announces Topline Data from Phase 3 INTUNE Study Evauating Pitolisant in Patients with Idiopathic Hypersomnia. News Release. Harmony Biosciences. Published October 13, 2023. Accessed February 19, 2025. https://www.harmonybiosciences.com/newsroom/harmony-biosciences-announces-topline-data-from-phase-3-intune-study
10. PTC Therapeutics Announces FDA Acceptance and Priority Review for Vatiquinone NDA for the Treatment of Children and Adults with Friedreich's Ataxia. News release. PTC Therapeutics. February 19, 2025. Accessed February 19, 2025. https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-fda-acceptance-and-priority-review-for-vatiquinone-nda-for-the-treatment-of-children-and-adults-with-friedreichs-ataxia-302379909.html
11. Entrada Therapeutics Announces FDA Removal of Clinical Hold on ENTR-601-44. News Release. Entrada Therapeutics. Published February 24, 2025. Accessed February 24, 2025. https://ir.entradatx.com/news-releases/news-release-details/entrada-therapeutics-announces-fda-removal-clinical-hold-entr
12. Medtronic earns U.S. FDA approval for the world's first Adaptive deep brain stimulation system for people with Parkinson's. News release. Medtronic. February 24, 2025. Accessed February 24, 2025. https://news.medtronic.com/2025-02-24-Medtronic-earns-U-S-FDA-approval-for-the-worlds-first-Adaptive-deep-brain-stimulation-system-for-people-with-Parkinsons