The U.S. Food and Drug Administration (FDA) has been active in recent months, issuing a series of decisions regarding potential new therapeutic agents for neurological and rare diseases. These actions include granting approvals, breakthrough therapy designations, and placing clinical holds on investigational new drug applications.
Breakthrough Therapy Designation for STK-001 in Dravet Syndrome
Stoke Therapeutics' investigational antisense agent STK-001, also known as zorevunersen, received breakthrough therapy designation from the FDA for the treatment of genetically confirmed Dravet syndrome (DS), a rare epilepsy disorder. The designation was granted on December 4, and the company is in discussions with the agency regarding plans for a phase 3 registrational study, expected to be released by the end of the year. Zorevunersen is designed to upregulate NaV1.1 protein expression by leveraging the non-mutant copy of the SCN1A gene, aiming to restore physiological NaV1.1 levels and reduce both seizures and non-seizure comorbidities. According to Shamim Ruff, chief regulatory affairs officer at Stoke, clinical data suggests that zorevunersen has the potential to demonstrate substantial improvement over current treatments for Dravet syndrome.
Clene Receives FDA Guidance on CNM-Au8 for ALS
On December 10, Clene Nanomedicine announced that the FDA provided written guidance regarding a potential accelerated approval pathway for its investigational product CNM-Au8 in amyotrophic lateral sclerosis (ALS). Clene intends to follow the FDA’s recommendations, investigating whether additional data from ongoing compassionate use expanded access programs (EAPs) can substantiate the effect of CNM-Au8 on neurofilament light chain (NfL) decline. The company plans to include the additional data in an NDA submission under the accelerated approval pathway in mid-2025.
Accelerated Approval Pathway for AMT-130 in Huntington Disease
Also on December 10, uniQure announced that the FDA reached an agreement with the company on key elements of an accelerated approval pathway for its investigational gene therapy AMT-130 for patients with Huntington disease (HD). The FDA concurred that data from the ongoing phase 1/2 clinical trials of AMT-130, utilizing a natural history external control as a comparator, could serve as the primary basis for a biologics license application submission under the accelerated approval pathway. The agency agreed that the Composite Unified Huntington’s Disease Rating Scale (cUHDRS) could be utilized as an intermediate clinical end point, with reductions in neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) to provide supportive evidence of therapeutic efficacy for the accelerated approval submission.
Breakthrough Therapy Designation for Tolebrutinib in Multiple Sclerosis
Sanofi's tolebrutinib, an investigational Bruton’s tyrosine kinase (BTK) inhibitor, received breakthrough therapy designation from the FDA on December 13 for patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS). The designation was based on findings from the HERCULES phase 3 study, which showed that treatment with tolebrutinib delayed the time to onset of 6-month confirmed disability progression (CDP) by 31% compared with placebo (HR, 0.69; 95% CI, 0.55-0.88; P = .0026) in patients with nrSPMS. Erik Wallström, MD, PhD, global head of neurology development at Sanofi, noted that clinicians should be aware of the risk of drug-induced liver injury with this compound class, requiring intense monitoring.
Clinical Hold on PGN-EDO51 Study in Duchenne Muscular Dystrophy
On December 16, the FDA placed a clinical hold on PepGen’s investigational new drug application for its phase 2 CONNECT2-EDO51 study, assessing PGN-EDO51 in patients with Duchenne muscular dystrophy (DMD). The company noted that the CONNECT2 trial, a 25-week multinational, double-blind, placebo-controlled trial with multiple ascending doses, is currently open in the United Kingdom. PepGen intends to work closely with the FDA to address their questions on the application to initiate CONNECT2 as expeditiously as possible.
FDA Approves Mesoblast’s Remestemcel-L for Steroid-Refractory GvHD
On December 18, the FDA approved Mesoblast’s allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy remestemcel-L for the treatment of steroid refractory acute graft versus host disease (GvHD) in children aged 2 months or older. The product is the first MSC therapy to have been approved by the FDA and will be marketed under the name Ryoncil.
Fast Track Designation to SC291 CAR T-Cell Therapy for SLE
Sana Biotechnology’s investigational chimeric antigen receptor (CAR) T-cell therapy, known as SC291, has been granted fast track designation by the FDA for the treatment of relapsed or refractory systemic lupus erythematosus (SLE), including both lupus nephritis and extrarenal lupus.
FDA Clears IND for Trial Assessing Gene Therapy SGT-212 in Friedreich Ataxia
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.
FDA Grants Breakthrough Therapy Designation to Tividenofusp Alfa for Hunter Syndrome
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.
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.
FDA Grants Priority Review to FcRn Inhibitor Nipocalimab for Myasthenia Gravis
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.
FDA Accepts sNDA for Higher Dosing Regimen of Nusinersen for Spinal Muscular Atrophy
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).
FDA Approves Vertex Pharmaceuticals' Suzetrigine for Acute Pain Management
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.
FDA Approves Axsome Therapeutics’ AXS-07 for Migraine Treatment
On the same day, January 30, the FDA 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.
