FDA Action Update, September 2024: Approvals, Designations, and Clearances

The FDA was busy in September 2024, making a number of decisions on potential new therapeutic agents including granting approvals, designations, new drug application acceptances, letter of support, and clearances.

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 Cortechs.ai’s NeuroQuant 5.0 Software for Quantification and Segmentation of ARIA-E and ARIA-H

Early in the month, on September 3, the FDA granted 510(k) clearance for Cortechs.ai’s NeuroQuant 5.0 software, allowing for advanced segmentation and quantification capabilities for MRI lesions associated with T2*-weighted gradient recalled echo and susceptibility weighted imaging. This latest software development supports clinicians in the enhancement of segmentation for amyloid-related imaging abnormalities (ARIA) in patients who are undergoing antiamyloid treatment for Alzheimer disease (AD).¹

Cortechs.ai noted that the update improves visualization and calculations of lesions with new improved deep learning-based technology. The technology offers providers with insights to support more specific and data-driven care for the management of neurological conditions such as traumatic brain injury (TBI), cerebral amyloid angiopathy, ARIA-E, and ARIA-H. The company also noted that the integration of susceptibility-sensitive MRI sequences in this new update could redefine industry standards, warranting unparalleled accuracy in the segmentation and quantification for even the tiniest lesions in the brain.

"Receiving FDA clearance for NeuroQuant 5.0 is a testament to Cortechs.ai's relentless drive to innovate and lead the industry in imaging-based AI technologies," Kyle Frye, CEO at Cortechs.ai, said in a statement.¹ "With this release, we are transforming the way radiologists and neurologists approach neurological evaluations, helping to ensure more accurate and timely diagnoses for patients. This marks our 5th FDA approved product, again signifying our pole position as the leader in quantitative AI imaging in both neurology and oncology."

FDA Grants Breakthrough Therapy Designation to Edaravone Dexborneol Combination Therapy for Acute Ischemic Stroke

On the same day on September 3, the FDA granted breakthrough therapy designation to Simcere Pharmaceuticals’ edaravone and dexborneol sublingual tablets (Sanbexin) for the treatment of acute ischemic stroke (AIS), becoming the first innovative drug globally to be given this designation in stroke by the agency.² The formulation of the brain cytoprotective agent, composed of 2 active ingredients with synergistic anti-oxidant and anti-inflammatory effects, can quickly disintegrate once in contact with salvia placed under the tongue, being absorbed into the blood.

This designation was based on the data published in JAMA Neurology from the phase 3 TASTE-SL study (NCT04950920) which demonstrated that treatment with the medication improved the rate of functional outcomes in patients with AIS who presented within 48 hours.³ In the trial, investigators randomly assigned those with AIS to edaravone dexborneol (n = 450) or placebo (edaravone, 0 mg; dexborneol, 60 ug) twice daily for 14 days with follow-up that lasted until 90 days. At the conclusion of the study, good functional outcome, defined as modified Rankin Scale (mRS) scores of 1 or less, were achieved in 64.4% of those on active treatment vs 54.7% of those on placebo (OR, 1.50; 95% CI, 1.15-1.95; P = .003).

"Sanbexin sublingual tablets is effective in improving neurological function recovery and independent living ability of ischemic stroke patients after treatment and apply to a variety of treatment scenarios,” senior author Dongsheng Fan, MD, PhD, the director of the neurological department at Peking University Third Hospital and a professor of neurology at Peking University, said in a statement.⁴ “This phase 3 study of Sanbexin sublingual tablet also provides a high-quality evidence-based basis for clinical brain cell protection, which provides a strong guarantee for stroke treatment."

FDA Accepts Resubmitted New Drug Application for Migraine Treatment AXS-07

A day later, on September 4, the FDA accepted Axsome Therapeutics’ resubmitted new drug application (NDA) for its novel agent AXS-07 as a treatment for acute migraine. The agency has given the oral, rapidly absorbed, multi-mechanistic investigational medicine a Prescription Drug User Fee Act (PDUFA) action goal date of January 31, 2025.⁵

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 May 2022, the company received a complete response letter for its NDA submission of AXS-07, citing issues related to the chemistry, manufacturing, and controls considerations. At the time, the agency did not request any new clinical trials to be conducted.⁶

FDA Supports Alpha-Synuclein Seed Amplification Assay Biomarker for Clinical Trials in Parkinson Disease

About a few days later, on September 9, the FDA issued a letter of support for using the α-synuclein seed amplification assay (αSyn-SAA) biomarker in clinical trials for Parkinson disease (PD) and related diseases. This decision comes following a multi-stakeholder collaboration between The Michael J. Fox Foundation for Parkinson's Research (MJFF) and the Critical Path Institute (C-Path) to advance PD therapeutics using this recently discovered biomarker.⁷

In the letter, the agency highlighted that its support comes from evidence gathered in the Parkinson's Progression Markers Initiative (PPMI), a longitudinal observational study sponsored by MJFF. The FDA noted that its decision to encourage use of αSyn-SAA also relied on other global studies across industry and academia, which represented the large amount of data as well as the applied collaboration used to validate the tool.

“The biomarker, now with the support of the FDA, will lead to faster, more effective clinical trials for Parkinson’s disease. Researchers can design trials that target specific aspects of disease biology with confidence that participants in the study have similar, important biological features. We anticipate this will speed along potential therapies already in early stages of the pipeline, while also attracting new or sustained interest from drugmakers. Our laser-focused goal remains the same — placing better therapies and a cure in the hands of people and families with Parkinson's," Todd Sherer, PhD, MJFF's chief mission officer, told NeurologyLive^®. "Working collaboratively together with partners — people and families living with PD, neuroscience and clinical leaders, industry experts, federal research funders (i.e., the National Institutes of Health), disease-focused nonprofit organizations and regulatory authorities — we are able to leverage the incredible amount of knowledge and expertise in the space. We believe bringing the field together is the fastest way to improve its outcomes.”

FDA Approves Subcutaneous Formulation of Ocrelizumab for Relapsing and Progressive Multiple Sclerosis

A couple of days later, on September 13, the FDA approved a new subcutaneous formulation of ocrelizumab (Ocrevus; Roche), a humanized monoclonal antibody designed to target CD20-positive B cells, as a treatment for relapsing forms of multiple sclerosis (MS) and primary progressive MS (PPMS), its original indication. Marketed as Zunovo, this expands on the administration options of ocrelizumab, which was originally approved in 2017 as an infusion.⁸

The belief is that a subcutaneous administration of ocrelizumab will provide greater treatment flexibility and additional treatment options for patients and healthcare providers. This was the second approval for subcutaneous ocrelizumab, following the European Commission’s decision to do so in early July.

"Ocrevus Zunovo gives patients and providers another option for receiving Ocrevus, building on a decade of robust safety and efficacy data for Ocrevus in multiple sclerosis," Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in a statement.⁸ "Today’s approval may offer greater flexibility for healthcare providers and people living with multiple sclerosis, based on their individual treatment needs."

FDA Approves Zevra Therapeutics’ Arimoclomol as First Treatment for Niemann-Pick Disease Type C

About a week later, on September 20, the FDA granted approval of Zevra Therapeutics’ arimoclomol (Miplyffa), an oral medication, for the treatment of neurological symptoms associated with Niemann-Pick disease type C (NPC) in adults and children 2 years of age and older. The treatment, which is combined with the enzyme inhibitor miglustat, becomes the first drug approved by the agency to treat patients with this condition.^9,10

The approval was based on data from a randomized, double-blind, placebo-controlled 12-month trial assessing arimoclomol among patients 2 to 19 years of age who had a molecularly confirmed diagnosis of NPC. In the trial, investigators randomized 50 patients 2:1 to treatment with weight-adjusted arimoclomol (31-mg to 124-mg) or placebo orally 3 times per day.

Among all the participants in the trial, 39 of them received miglustat as background treatment (78%). Findings showed that patients treated with arimoclomol, in combination with miglustat, had a slower disease progression, as shown by a 0.2 reduction from baseline on the rescored 4-domain NPC Clinical Severity Scale compared with 1.9 points of progression in the placebo group.

“NPC is a serious disease that leads to enormous adverse impacts on patients and families. Despite extensive research efforts, there have not been approved treatments to meet the significant needs of patients,” Janet Maynard, MD, MHS, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in the FDA’s Center for Drug Evaluation and Research, said in a statement.⁹ “The first-ever approval of a safe and effective drug option for NPC will undoubtedly support the essential medical needs of those suffering.”

FDA Approves Stand-Alone Therapy Levacetylleucine for Niemann-Pick Disease Type C

Less than a week later, on September 25, the FDA approved IntraBio’s levacetylleucine, an agent that ameliorates lysosomal and metabolic dysfunction, as a stand-alone treatment of neurological manifestations in Niemann-Pick disease type C (NPC) among adults and pediatric patients weighing at least 15 kg.^11,12 Marketed as Aqneursa, the treatment becomes the second FDA-approved therapy indicated for NPC following the recently authorized arimoclomol (Miplyffa; Zevra Therapeutics).

The approval was based on data from the phase 3 double-blind, placebo-controlled, crossover trial IB1001-301 trial (NCT05163288), which investigated levacetylleucine among 60 patients aged between 5 years and 67 years of age with NPC over 12 weeks. In the trial, levacetylleucine met its primary efficacy end point, measured by the functional version of the Scale for the Assessment and Rating of Ataxia (fSARA), and all secondary end points. Published in the New England Journal of Medicine, patients who received levacetylleucine showed a greater improvement in fSARA score with a mean treatment difference of -0.4 (95% CI, -0.7to -0.2; P <.001) compared with placebo.¹³

"IntraBio has been dedicated to bringing novel treatments to patients with extremely high unmet medical needs like NPC, and today we celebrate a major milestone in this tremendous effort,” Mallory Factor, president and chief executive officer at IntraBio, said in a statement.¹¹ “Patients and families in the NPC community have long awaited an effective, FDA-approved treatment, and we are proud to bring hope to those affected by this devastating disease. We remain committed to ensuring that all patients who can benefit from this novel treatment will have the opportunity to do so. Based on our clinical research, we believe that Aqneursa may hold potential for treating other rare and common neurodegenerative and neurodevelopmental disorders, and we will continue to rapidly develop Aqneursa for these additional indications.”

REFERENCES
1. Cortechs.ai Receives FDA 510(k) Clearance for Groundbreaking NeuroQuant 5.0 Software, Expanding Support for Quantification of ARIA-E and ARIA-H. News Release. Published September 3, 2024. Accessed October 9, 2024. https://www.prnewswire.com/news-releases/cortechsai-receives-fda-510k-clearance-for-groundbreaking-neuroquant-5-0-software-expanding-support-for-quantification-of-aria-e-and-aria-h-302235486.html
2. Breakthrough Therapy designation for Sanbexin sublingual tablets granted by the United Stated Food and Drug Administration. News Release. Simcere Pharmaceuticals. Published September 3, 2024. Accessed October 9, 2024. https://en.simcere.com/news/detail.aspx?mtt=1470
3. Fu Y, Wang A, Tang R, et al. Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke: The TASTE-SL Randomized Clinical Trial [published correction appears in JAMA Neurol. 2024 Apr 1;81(4):425. doi: 10.1001/jamaneurol.2024.0883]. JAMA Neurol. Published online February 19, 2024. doi:10.1001/jamaneurol.2023.5716
4. Findings of a Phase III Clinical Study of Sanbexin® Sublingual Tablets Published in JAMA. News Release. Simcere Pharmaceuticals. February 20, 2024. Accessed October 9 2024. https://www.prnewswire.com/news-releases/findings-of-a-phase-iii-clinical-study-of-sanbexin-sublingual-tablets-published-in-jama-302066840.html
5. axsome therapeutics announces fda acceptance of nda resubmission for axs-07 for the acute treatment of migraine. News release. Axsome Therapeutics. September 4, 2024. Accessed October 9 , 2024. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-acceptance-nda-resubmission
6. Axsome Therapeutics Receives FDA Complete Response Letter for New Drug Application for AXS-07 for the Acute Treatment of Migraine. News release. Axsome Therapeutics. May 2, 2022. Accessed October 9, 2024. https://www.prnewswire.com/news-releases/axsome-therapeutics-receives-fda-complete-response-letter-for-new-drug-application-for-axs-07-for-the-acute-treatment-of-migraine-301537093.html
7. FDA Issues 'Letter of Support' Encouraging Use of Synuclein-based Biomarker, αSyn-SAA, in Clinical Trials in Parkinson's and Related Diseases. News Release. The Michael J. Fox Foundation for Parkinson's Research. Published September 9, 2024. Accessed October 9, 2024. https://www.michaeljfox.org/publication/fda-issues-letter-support-encouraging-use-synuclein-based-biomarker-asyn-saa-clinical
8. FDA Approves Ocrevus Zunovo™ as the First and Only Twice-a-Year 10-Minute Subcutaneous Injection for People With Relapsing and Progressive Multiple Sclerosis. Genentech. September 13, 2024. Accessed October 9, 2024. https://finance.yahoo.com/news/fda-approves-ocrevus-zunovo-first-172300395.html
9. FDA Approves First Treatment for Niemann-Pick Disease, Type C. News Release. FDA. Published September 20, 2024. Accessed October 9, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-niemann-pick-disease-type-c
10. Zevra Therapeutics’ MIPLYFFA™ (arimoclomol) Receives U.S. FDA Approval as Treatment for Niemann-Pick Disease Type C. News Release. Zevra Therapeutics. Published September 20, 2024. Accessed October 9, 2024. https://investors.zevra.com/news-releases/news-release-details/zevra-therapeutics-miplyffatm-arimoclomol-receives-us-fda1.
11. IntraBio Announces U.S. FDA Approval of AQNEURSA for the Treatment of Niemann-Pick Disease Type C. News Release. IntraBio. September 25, 2024. Accessed October 9, 2024. https://www.businesswire.com/news/home/20240925347296/en/IntraBio-Announces-U.S.-FDA-Approval-of-AQNEURSA-for-the-Treatment-of-Niemann-Pick-Disease-Type-C
12. FDA Approves New Drug to Treat Niemann-Pick Disease, Type C. News Release. FDA. Published September 24, 2024. Accessed October 9, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treat-niemann-pick-disease-type-c
13. Bremova-Ertl T, Ramaswami U, Brands M, et al. Trial of N-Acetyl-l-Leucine in Niemann-Pick Disease Type C. N Engl J Med. 2024;390(5):421-431. doi:10.1056/NEJMoa2310151