FDA’s April neurology actions: Auvelity approval, CRL for IV nimodipine, tremor device clearance, gene therapy date set

A packed April for neurology at the US Food and Drug Administration closed with a high-profile approval for Alzheimer’s care and a series of decisions that advanced, redirected, or reshaped other programs across rare disease, devices, and acute neurology.

On April 30, the FDA approved dextromethorphan hydrobromide and bupropion hydrochloride (Auvelity; Axsome Therapeutics) for agitation associated with Alzheimer’s disease, making it the first oral non-antipsychotic cleared for this indication. It is the second FDA-approved therapy for Alzheimer’s-related agitation; the antipsychotic brexpiprazole (Rexulti; Otsuka Pharmaceutical) was cleared in 2023.

The fixed-dose combination pairs dextromethorphan, which targets N-methyl D-aspartate and sigma-1 receptors, with bupropion, which inhibits CYP2D6 to sustain therapeutic dextromethorphan levels. The supplemental new drug application was supported by the phase 3 ADVANCE-1 and ACCORD-2 trials, which showed significant reductions in agitation severity compared with placebo.

Earlier in the month, on April 2, the FDA accepted a resubmitted biologics license application for UX111 (rebisufligene etisparvovec), an AAV9-based gene therapy for Sanfilippo syndrome type A. Manufacturer Ultragenyx said the agency set a Prescription Drug User Fee Act action date of September 19, 2026.

The resubmission follows a prior complete response letter that primarily cited chemistry, manufacturing, and controls issues rather than clinical efficacy concerns. If approved, UX111 could become the first disease-modifying treatment for this progressive, rare neurodegenerative disorder.

Device-based therapeutics also advanced. On April 15, the FDA cleared Cala kIQ Plus, an updated wearable neuromodulation system for essential tremor and Parkinson’s disease–related tremor, according to the manufacturer, Cala.

The transcutaneous afferent patterned stimulation system adds adaptive calibration and three customizable therapy modes to tailor treatment for essential tremor and for postural and kinetic hand tremor symptoms in Parkinson’s disease. Clearance was based on data presented at the American Academy of Neurology 2026 Annual Meeting.

Not all programs moved forward. On April 23, the FDA issued a complete response letter to Grace Therapeutics for GTx-104, an intravenous formulation of nimodipine intended for patients with aneurysmal subarachnoid hemorrhage, the company reported. The formulation aims to improve delivery consistency over oral nimodipine and potentially reduce risks related to food effects, drug–drug interactions, and dosing errors.

The letter cited deficiencies in the chemistry, manufacturing, and controls and nonclinical sections, including concerns about packaging-related leachables, toxicology risk assessments, and manufacturing processes. Grace Therapeutics said it plans to request a Type A meeting with the FDA to discuss a path forward.

The next milestones to watch include the September 19 action date for UX111 and Grace Therapeutics’ planned meeting with regulators, while Cala prepares to roll out its cleared device and Axsome Therapeutics moves to make Auvelity available for Alzheimer’s-related agitation.