FDA Action Update, April 2026: Acceptance, Clearance, and Complete Response Letter

The FDA was busy in April 2026, making a number of decisions on potential new therapeutic agents, including accepting a resubmission, granting a clearance, and issuing a complete response letter.

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, we’ve compiled all the updates here. The coverage includes the latest FDA approvals, new designations, submissions, resubmissions, and clinical trial initiations and holds.

FDA Accepts Ultragenyx's Resubmitted BLA for MPS IIIA Gene Therapy UX111

At the beginning of the month, on April 2, 2026, the FDA accepted Ultragenyx's resubmitted biologics license application (BLA) for UX111 (rebisufligene etisparvovec), an AAV9 vector–based gene therapy in development for mucopolysaccharidosis type IIIA (MPS IIIA), commonly known as Sanfilippo syndrome type A.¹

The new prescription drug user fee act (PDUFA) target action date has been established as September 19, 2026. The resubmission follows a complete response letter (CRL) issued by the FDA in July 2025 in response to an earlier BLA filing. Ultragenyx has indicated that the CRL identified a need for supplemental chemistry, manufacturing, and controls information, as well as observations stemming from inspections of the company's manufacturing facilities.

“The FDA’s acceptance of the BLA for UX111 brings us closer to the possibility of a first-ever therapy for Sanfilippo syndrome Type A—a milestone that we recognize cannot come soon enough for families facing this devastating diagnosis,” Emil D. Kakkis, MD, PhD, the chief executive officer and president of Ultragenyx, said in a statement.¹ “We appreciate the FDA’s prompt acceptance of the resubmission and look forward to working with the agency throughout its review in order to bring this treatment option to the Sanfilippo syndrome community as quickly as possible.”

Elecsys NfL Test Receives European Approval for Monitoring Neuroinflammation in Relapsing-Remitting Multiple Sclerosis

About a week later, on April 12, 2026, Roche announced that its Elecsys neurofilament light chain (NfL) test has received CE mark approval for detecting neuroinflammation in patients with relapsing-remitting multiple sclerosis (RRMS). The company noted that the blood-based assay is designed to provide clinicians with a less invasive method to monitor disease-related nerve cell injury and support clinical decision-making.²

Previously granted breakthrough device designation by the FDA, the Elecsys NfL test measures NfL, a protein released into the bloodstream during neuroaxonal damage. By quantifying this biomarker through a simple blood draw, the test offers insight into the biological processes underlying neuroinflammation in MS. According to the company, this approach may complement existing tools such as MRI and clinical assessments by providing additional data on disease activity.

“The CE mark for Elecsys NfL is an important moment for MS care, as it brings a CE‑marked blood test to detect neuroinflammation in relapsing‑remitting MS into everyday clinical practice. Clinicians can now access a standardised, in‑vitro diagnostic‑quality blood test that measures [NfL], a protein released during nerve cell injury, on widely used cobas instruments rather than relying only on specialised or research settings,” Ashton Harper, MD, Global Medical Affairs Lead for Neuroscience at Roche Diagnostics, told NeurologyLive.

FDA Clears Cala kIQ Plus for Essential Tremor and Parkinson Disease Hand Tremor

A few days later, on April 15, 2026, the FDA cleared Cala kIQ Plus, an updated wearable transcutaneous afferent patterned stimulation (TAPS) system, for temporary relief of action hand tremor in essential tremor (ET) and postural and kinetic hand tremor symptoms in Parkinson disease (PD).³

Developed by Cala Health, the next-generation device builds on the previously cleared Cala kIQ platform, incorporating new therapy modes and adaptive calibration designed to personalize stimulation and optimize tremor control. The clearance was granted through the 510(k) pathway based on substantial equivalence to the prior device, with updates primarily focused on software, calibration, and usability enhancements rather than a new pivotal efficacy trial.

“Cala continues to elevate the patient experience and therapy outcomes by advancing wearable neuromodulation technology that treats action hand tremor in essential tremor and Parkinson's disease. The Cala kIQ Plus system gives patients more control over how, when and where TAPS Therapy is delivered for tremor management," Deanna Harshbarger, MBA, chief executive officer at Cala, said in a statement.³ "We will present the latest data on Cala kIQ Plus at the American Academy of Neurology conference in Chicago."

FDA Issues Complete Response Letter for GTx-104 in Patients With Aneurysmal Subarachnoid Hemorrhage

Nearly 10 months after the submission of a new drug application (NDA), on April 23, 2026, the FDA issued a complete response letter (CRL) for Grace Therapeutics’ GTx-104, an injectable formulation of nimodipine, for the treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). The administration referenced items in the chemistry, manufacturing, and Controls (CMC) and non-clinical sections of the application.⁴

The cited items are related to leachables data for product packaging, non-clinical product toxicology risk assessments, and product manufacturing deficiencies at Grace Therapeutics’ contract manufacturing organization. The company stated in a press release that it believes it can address the CRL in a resubmission of its NDA and intends to request a Type A meeting with the FDA to clarify the path forward and determine the appropriate next steps.

“Potential FDA approval of our NDA for GTx-104 for the treatment of aSAH would represent the first meaningful innovation in the standard of care for these patients in more than 40 years,” Prashant Kohli, MD, chief executive officer of Grace Therapeutics, said in a statement.⁴ “We are confident in the robust data package supporting our NDA submission, and that the CMC issues identified by the FDA can be successfully addressed in our resubmission.”

CHMP Recommends BTK Inhibitor Tolebrutinib as Treatment for Nonrelapsing Secondary Progressive MS

A couple of days later, on April 24, 2026, data from the phase 3 HERCULES trial led the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) to recommend approval of tolebrutinib (Cenrifki; Sanofi) for patients with nonrelapsing secondary progressive multiple sclerosis (nrSPMS), marking a potential new option in a population with limited disease-modifying therapies.⁵

Secondary progressive MS without relapses is characterized by gradual and irreversible accumulation of disability, often driven by compartmentalized inflammation within the central nervous system. Unlike relapsing forms of MS, where peripheral immune activity is more prominent, nrSPMS is thought to be sustained by chronic microglial activation and smoldering inflammation behind an intact blood-brain barrier, contributing to progressive neurodegeneration.

Tolebrutinib is an oral, brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor designed to target both peripheral B cells and innate immune signaling within the CNS. By inhibiting BTK, the therapy may reduce proinflammatory signaling in microglia and B cells, addressing a key mechanism believed to underlie disability progression in progressive MS. The agent has previously received nreakthrough therapy designation from the FDA for nrSPMS based on early evidence of efficacy in slowing disability accumulation.

FDA Approves AXS-05 as New Treatment for Alzheimer Disease Agitation

At the end of the month, on April 30, 2026, the FDA approved Axsome Therapeutics’ AXS-05, an investigational, orally administered combination of dextromethorphan HBr and bupropion HCI, as a treatment for agitation in patients with dementia because of Alzheimer disease (AD). Marketed as Auvelity, the drug is the second FDA-approved treatment specific to treat agitation symptoms patients with AD.

The supplemental new drug application (sNDA) for AXS-05 was supported by 4 randomized, double-blind trials: ADVANCE-1 (NCT03226522), ADVANCE-2 (NCT05557409), ACCORD-1 (NCT04797715), and ACCORD-2 (NCT04947553). ACCORD-2 and ADVANCE-2, the most notable of the studies, included 167 and 408 patients, respectively, testing the efficacy and safety of AXS-05 in AD agitation.

“Agitation is highly prevalent in patients with Alzheimer’s disease and among the most burdensome aspects of the disease for patients and families. Alzheimer’s disease agitation is associated with accelerated cognitive decline, placement in assisted living and long-term care facilities, and increased mortality risk,” Jeffrey Cummings, MD, ScD, Chambers-Grundy Professor of Brain Sciences, UNLV Kirk Kerkorian School of Medicine, said in a statement.⁶ “Treatment for agitation associated with Alzheimer disease dementia has been a critical unmet medical need. The approval of Auvelity for this condition has the potential to play an important role in patient care for this challenging and impactful symptom of Alzheimer disease.”

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REFERENCES
1. Ultragenyx announces U.S. FDA acceptance of BLA resubmission for UX111 AAV gene therapy to treat sanfilippo syndrome type A (MPS IIIA). News release. Ultragenyx Pharmaceutical Inc. April 2, 2026. Accessed April 30, 2026. https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-us-fda-acceptance-bla-resubmission-ux111
2. Roche receives CE mark for new Elecsys NfL blood test to detect neuroinflammation in multiple sclerosis. News release. Roche. April 12, 2026. Accessed April 30, 2026. https://www.roche.com/media/releases/med-cor-2026-04-13
3. Cala Health. Cala announces FDA clearance of its next generation TAPS therapy wearable device for essential tremor and Parkinson’s disease. News release. April 15, 2026. Accessed April 30, 2026. https://www.prnewswire.com/news-releases/cala-announces-fda-clearance-of-its-next-generation-taps-therapy-wearable-device-for-essential-tremor-and-parkinsons-disease-302742780.html
4. Grace Therapeutics Provides Regulatory Update on New Drug Application for GTx-104. Grace Therapeutics. News Release. April 23, 2026. Accessed April 30, 2026. https://www.gracetx.com/investors/news-events/press-releases/detail/303/grace-therapeutics-provides-regulatory-update-on-new-drug-application-for-gtx-104
5. Cenrifki (tolebrutinib) recommended for EU approval by CHMP for secondary progressive multiple sclerosis. News release. Sanofi. April 24, 2026. Accessed April 30, 2026. https://www.globenewswire.com/news-release/2026/04/24/3280641/0/en/press-release-sanofi-s-cenrifki-tolebrutinib-recommended-for-eu-approval-by-the-chmp-to-treat-secondary-progressive-multiple-sclerosis-without-relapses.html
6. Axsome Therapeutics Announces FDA Approval of AUVELITY® (dextromethorphan HBr and bupropion HCl) for the Treatment of Agitation Associated with Dementia due to Alzheimer’s Disease. News release. Axsome Therapeutics. April 30, 2026. Accessed April 30, 2026. https://www.globenewswire.com/news-release/2026/04/30/3285345/33090/en/axsome-therapeutics-announces-fda-approval-of-auvelity-dextromethorphan-hbr-and-bupropion-hcl-for-the-treatment-of-agitation-associated-with-dementia-due-to-alzheimer-s-disease.html