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FDA Action Update, January 2025: Approvals, Clearances, and Designations
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- Solid Biosciences' SGT-212 gene therapy for Friedreich ataxia received FDA clearance, targeting neurologic and systemic manifestations via dual administration routes.
- Annovis Bio's phase 3 Alzheimer’s trial protocol was accepted, aiming to accelerate development and support a New Drug Application for buntanetap.
Catch up on any of the neurology news headlines you may have missed over the course of January 2025, compiled all into one place by the NeurologyLive® team.
The FDA was busy in January 2025, making a number of decisions on potential new therapeutic agents including granting approvals, clearances, and acceptances, 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 Clears IND for Trial Assessing Gene Therapy SGT-212 in Friedreich Ataxia
Early in the month, on January 7, the FDA gave clearance to Solid Biosciences’ investigational new drug application (IND) for SGT-212, an adeno-associated virus (AAV)-based gene therapy candidate for Friedreich ataxia (FA). A phase 1b, first-in-human, open-label, dose-finding trial featuring non-ambulatory and ambulatory adults with FA is expected to begin the second half of 2025.1
SGT-212 is designed to deliver full-length human frataxin (Fxn) via a dual route of administration: intradentate nucleus (IDN) infusion, using an MRI-guided device, followed by an intravenous (IV) infusion to increase therapeutic Fxn levels in the cerebellar dentate nuclei and in the cardiomyocytes, respectively. A unique agent, SGT-212 is geared towards treating both the neurologic and systemic clinical manifestations of FA to address the full spectrum of disease progression.
"SGT-212 has been intentionally designed to enable highly targeted delivery of our gene therapy to both the dentate nuclei and cardiac tissue," Bo Cumbo, president and chief executive officer at Solid, said in a statement.1 "The IND was supported by a robust preclinical package demonstrating safe transduction and frataxin expression in these target tissues, with significant restoration of neurologic function and reversal of the cardiac implications of the disorder in mice."study."
FDA Accepts Amended Protocol for Phase 3 Trial of Buntanetap in Alzheimer Disease
On the same day, January 7, the FDA accepted an updated protocol for Annovis Bio’s pivotal phase 3 Alzheimer disease (AD) study testing the therapeutic potential of its investigational agent buntanetap, an orally available small molecule.2
In October 2024, the company received FDA approval to launch its phase 3 trials for AD after phase 2/3 (NCT05686044) results highlighted cognitive benefits in patients with early-stage AD. In the original launch, the phase 3 study was intended to be 2 separate trials. Slated to begin this month, the newly revised phase 3 study is now comprised of a 6-month symptomatic analysis along with a 12-month assessment to study disease-modifying impacts of the agent.
"This consolidated protocol will accelerate the development timeline while maintaining the scientific rigor necessary to advance buntanetap as a treatment for AD," Maria Maccecchini, PhD, founder, president, and chief executive officer at Annovis, said in a statement.2 "With this design, we can leverage the 6-month symptomatic data to potentially support a New Drug Application (NDA) filing, all while continuing the same study seamlessly to assess long-term disease-modifying outcomes. We are excited to move forward with this approach, which brings us closer to delivering a novel treatment to patients in need."
FDA Clears Phase 2 Trial of Lorundrostat for Obstructive Sleep Apnea and Hypertension
A day later, on January 8, the FDA approved Mineralys Therapeutics' investigational new drug (IND) application for a phase 2 trial assessing the efficacy of lorundrostat in patients with moderate-to-severe obstructive sleep apnea (OSA) and hypertension. The study, a placebo-controlled, crossover trial, is expected to include 40 individuals with mild-to-moderate OSA and begin in the first quarter of 2025.3
The study will test whether lorundrostat, taken at 50 mg once daily in the evening, may alleviate the severity of upper airway obstruction and reduce nocturnal hypertension. Investigators will use absolute change in the frequency of apnea-hypopnea episodes as the primary outcome, with secondary objectives that include quantifying blood pressure (BP) during the night using a continuous BP monitor without the benefit of continuous positive airway pressure (CPAP). Other standard patient reported outcomes, specific to OSA, will also be reported.
"We are pleased to announce the OSA clinical development program for lorundrostat. This program aligns with our strategy to develop lorundrostat in conditions driven by dysregulated aldosterone, with poor cardiovascular outcomes and few treatment options," Jon Congleton, chief executive officer at Mineralys, said in a statement.3 "We believe suppression of aldosterone production by lorundrostat has the potential to reduce the nocturnal hypertension driving adverse cardiovascular outcomes. In addition, lorundrostat is anticipated to reduce the severity of upper airway obstruction and associated OSA symptoms such as daytime sleepiness and cognitive impairment.”
FDA Grants Breakthrough Therapy Designation to Denali’s Tividenofusp Alfa for Hunter Syndrome
On the same day, on January 8, the FDA granted breakthrough therapy designation to Denali Therapeutics’ investigational therapy tividenofusp alfa, also known as DNL310, for the treatment of patients with Hunter syndrome. The company noted that it anticipates submitting a biologics license application (BLA) for the agent in early 2025 for regulatory review under the accelerated approval pathway.4
In September 2024, the company announced that it completed a successful meeting with the FDA’s Center for Drug Evaluation and Research (CDER) division outlining a path towards potential accelerated approval for the tividenofusp alfa in Hunter syndrome, also known as mucopolysarcharidosis type II (MPS) syndrome. In the meeting, both parties agreed that cerebrospinal fluid heparan sulfate (CSF HS) is likely to predict clinical benefit and can serve as a surrogate end point for its accelerated approval.
“My reaction was elation for what this could mean for the Hunter syndrome community and gratitude for the FDA's recognition of the potential of tividenofusp alfa as a meaningful treatment option for individuals with Hunter syndrome.” Carole Ho, MD, chief medical officer at Denali Therapeutics, told NeurologyLive®.“Tividenofusp alfa is uniquely designed to optimize enzyme delivery to both brain and body. It is the only candidate therapy to normalize key biomarkers, CSF HS, urine HS, and neurofilament light (NfL), in a lysosomal storage disease.”
FDA Grants Fast Track Designation to Anti-Tau Therapy Posdinemab
Still on January 8, the FDA has assigned fast track designation to Johnson & Johnson’s investigational tau-directed monoclonal antibody posdinemab as a potential treatment for patients with early-stage AD. Anti-tau therapies have shown promise in slowing disease progression by addressing tau pathology, a key driver of cognitive decline in later stages of the disease.5
Posdinemab is currently being investigated in the phase 2b AuTonomy study (NCT04619420), a double-blind, placebo-controlled, randomized, parallel-group, common-close study that it is the first to employ a plasma biomarker as a screening tool. The study, which assesses the effect of 2 doses of posdinemab (low or high dose) or placebo, every 4 weeks over a 104-week treatment period, includes patients with symptomatic AD who meet clinical and plasma phosphorylated (p-tau)217 criteria followed by intermediate levels of tau burden on tau PET.
"As the average age of the global population increases, the number of people impacted by this debilitating progressive disease continues to rise. Alzheimer disease places a substantial emotional and financial burden on patients and their loved ones and has a significant economic and societal impact," Bill Martin, PhD, Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine, said in a statement.5 "Posdinemab has the potential to slow the spread of tau pathology in the brain - which may slow cognitive decline. The FDA’s Fast Track designation reflects the urgent unmet need for new treatment options for the millions living with AD."
FDA Grants Priority Review to FcRn Inhibitor Nipocalimab for Myasthenia Gravis
A day later, on January 9, the FDA granted priority review to Johnson & Johnson’s investigational monoclonal antibody nipocalimab as a potential treatment for patients with myasthenia gravis (MG), an autoantibody disease. Nipocalimab, designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobulin G (IgG) antibodies, remained currently under review by the European Medicines Agency.6
If approved, nipocalimab will be available for antibody-positive patients with MG, including those with anti-acetylcholine (AChR), anti-muscle-specific kinase antibody (MuSK), and anti-low density lipoprotein-related protein 4 (LRP4) subtypes. The agent’s application is supported by the phase 3 Vivacity-MG3 study (NCT04951622), a large-scale trial that demonstrated nipocalimab’s superiority over placebo plus standard-of-care (SOC) therapy over a 24-week period.
"We welcome the FDA's decision to grant Priority Review for the treatment of generalized myasthenia gravis, which underscores the need for additional treatment options in a broad population of people living with gMG," Katie Abouzahr, MD, vice president, Autoantibody Portfolio and Maternal Fetal Immunology Disease Area Leader at Johnson & Johnson Innovative Medicine, said in a statement.6 "We are committed to working closely with the FDA to help bring nipocalimab as a potential treatment to certain patients living with gMG, and we especially thank the participants in the Phase 2 and 3 studies."
FDA Accepts BLA for Subcutaneous Autoinjector Formulation of Lecanemab
A couple of days later, on January 13, the FDA accepted Eisai’s BLA for lecanemab-irmb (Leqembi) subcutaneous autoinjector (SC-AI) for weekly maintenance dosing in patients with early-stage AD. The agency has set a PDUFA action date for August 31, 2025, for a decision to be made.7
If approved by the FDA, lecanemab would become the first AD treatment available for at-home subcutaneous administration using an autoinjector, with injections averaging 15 seconds. Following the biweekly intravenous (IV) initiation phase, patients would transition to weekly 360 mg subcutaneous maintenance doses to sustain clinical and biomarker benefits. Lecanemab, which received traditional approval in July 2023, was originally approved in a 100 mg/mL injection for patients with mild cognitive impairment (MCI) or mild dementia stage of the disease, the population in which treatment was initiated in clinical trials.
The belief is that the new SC-AI will hopefully ease patient care, as well as reduce the need for hospital or infusion site visits and nursing care for IV administration. Data from the pivotal phase 3 Clarity AD trial (NCT03887455)—the study it was originally approved off of—as well as its open-label extension and modeling of observed data, will support the SC-AI’s BLA.
Spinogenix's SPG601 Receives FDA Fast Track Designation for Fragile X Syndrome
On the same day, January 13, the FDA granted fast track designation to Spinogenix’s investigational therapy SPG601 for the treatment of patients with Fragile X syndrome (FXS), a leading cause of genetic autism. Spinogenix also announced that it recently completed its phase 2 study (NCT06413537) assessing the agent in adult men with FXS, with topline results anticipated by end of the first quarter in 2025.8
The phase 2 trial is a randomized, double-blind, placebo-controlled crossover study that evaluated a single dose of SPG601 compared with a placebo in patients with FXS. Spinogenix noted that the trial was specifically designed to assess significant brain target engagement in first-in-human FXS studies, utilizing validated neurophysiological markers of brain activity. These markers have been rigorously validated over the past decade by principal investigator Erickson and his team, with support from the National Institutes of Health Centers for Collaborative Research in Fragile X program.
"Fragile X syndrome profoundly impacts patients and families yet remains without FDA-approved treatments. Beyond intellectual disability, individuals with FXS often experience debilitating symptoms that severely affect their quality of life, including severe anxiety, hyperactivity and attention deficit, sensory hypersensitivity, and at times irritability marked by aggression and self-injurious behavior," Craig Erickson, MD, chief medical advisor at Spinogenix and associate professor in the division of child and adolescent psychiatry at Cincinnati Children's, told NeurologyLive®.
FDA Accepts sNDA for Higher Dosing Regimen of Nusinersen for Spinal Muscular Atrophy
About a week later, on January 23, the FDA accepted Biogen’s supplemental NDA (sNDA) for a higher, potentially more efficacious dose regimen of nusinersen (Spinraza) for patients with spinal muscular atrophy (SMA). The company also reported that the European Medicines Agency (EMA) has validated the application for the higher dose as well.9
The higher dose nusinersen regimen includes a faster loading phase with two 50 mg doses administered 14 days apart, followed by a higher maintenance dose of 28 mg every 4 months, compared to the standard approved nusinersen regimen. The regulatory submission was based on findings from the phase 2/3 DEVOTE study (NCT04089566), a randomized, controlled, dose-escalating trial that comprised of 145 participants across ages and SMA types at 42 sites around the globe.
"We are pleased to announce that our applications for the higher dose regimen of nusinersen are now under review in the US and Europe," Stephanie Fradette, PharmD, head of the neuromuscular development unit at Biogen, said in a statement.9 "This milestone reflects our steadfast commitment to advance treatment options for individuals with SMA, and we expect that this higher dose regimen will offer meaningful benefits to patients and their families. We are deeply thankful for the unwavering support of the trial participants, their families, site staff, and the SMA community without whom these advancements would not have been possible."
FDA Approves New IV Maintenance Dosing for Alzheimer Treatment Lecanemab
A couple of days later, on January 26, the FDA has approved the Eisai’s intravenous (IV) maintenance dosing for lecanemab-irmb, an antiamyloid medication for patients with early-stage AD. As part of the approval, patients completing biweekly IV initiation would receive IV doses once every 4 weeks to maintain effective clearance of toxic protofibrils, thus preventing neuronal injury.10
The supplemental BLA (sBLA) for the latest IV maintenance dosing was based on modeling of observed data from the phase 2 study (Study 201; NCT01767311) and its open-label extension (OLE), as well as the phase 3 Clarity AD trial (Study 301; NCT03887455) and its OLE study. For context, lecanemab was originally approved under accelerated approval pathway using Study 201, and was later granted traditional approval in July 2023 based on data from Study 301, the confirmatory trial.11
Originally approved as a 100 mg/mL injection for patients with mild cognitive impairment (MCI) or mild dementia stages of the disease, lecanemab’s new once-monthly dosing regimen is believed to be less burdensome and easier for patients while maintaining clinical and biomarker benefits. The sBLA submission for this new maintenance dosing was submitted in April 2024, with the FDA accepting it for review less than 3 months later.
FDA Approves Vertex Pharmaceuticals' Suzetrigine for Acute Pain Management
At the end of the month, on January 30, the FDA approved suzetrigine (Vertex Pharmaceuticals), an oral selective NaV1.8 pain signal inhibitor, to treat patients who experience moderate-to-severe acute pain. Marketed as Journavx, the novel, non-opioid therapy becomes the first new class of medicine to treat acute pain in over 20 years.12
The NDA for suzetrigine, formally known as VX-548, was based on data from a phase 3 program that included 2 randomized, double-blind, placebo-controlled trials; 1 post abdominoplasty surgery and 1 post bunionectomy surgery. The program also included a single arm safety and efficacy study that included patients with a wide range of surgical and non-surgical pain conditions.
"Today’s approval is an important public health milestone in acute pain management," Jacqueline Corrigan-Curay, JD, MD, acting director of the FDA's Center for Drug Evaluation and Research, said in a statement.12 "A new non-opioid analgesic therapeutic class for acute pain offers an opportunity to mitigate certain risks associated with using an opioid for pain and provides patients with another treatment option. This action and the agency’s designations to expedite the drug’s development and review underscore FDA’s commitment to approving safe and effective alternatives to opioids for pain management."
FDA Approves Axsome Therapeutics’ AXS-07 for Migraine Treatment
On the same day, January 30, and months after the FDA accepted Axsome Therapeutics’ resubmission of its NDA in September 2024, the agency approved AXS-07, an oral, rapidly absorbed, multi-mechanistic agent, as a new acute treatment of migraine with or without aura in adults. Marketed as Symbravo, the company noted that it anticipates AXS-07 to be commercially available in the United States in approximately 4 months.13
AXS-07, a novel agent, is thought to act by inhibiting calcitonin gene-related peptide (CGRP) release, reversing CGRP-mediated vasodilation, and inhibiting neuroinflammation, pain signal transmission, and central sensitization. The agent, which consists of meloxicam and rizatriptan, is enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which results in faster absorption and longer plasma half-life.
"In terms of use in clinical practice, we want to treat our patients with the simplest, most effective acute treatments that we're able to offer them. So, you would not use a combination triptan and non-steroidal product in a patient whose treatment needs were fully met, either by a triptan alone or by a non-steroidal anti-inflammatory alone," Richard B. Lipton, MD, professor of neurology and director of the Montefiore Headache Center at Albert Einstein College of Medicine, told NeurologyLive® in a recent interview. "In fact, the design for individuals with unmet needs on single, monotherapy acute treatments was specifically a reflection of the fact that those are the patients who need combination therapy. I think that's something most prescribers would do and should do."
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