FDA Action Update, February 2024: Clearance, Priority Review, and Designation

The FDA was busy in February 2024, making a number of decisions on potential new therapeutic agents including a clearance for a clinical trial, granting a priority review for efficacy supplement, and granting a fast track designation.

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 Gene Therapy Candidate ETX101 in Dravet Syndrome

Earlier in the month, on February 6, the FDA cleared Encoded Therapeutics’ investigational new drug (IND) application for ETX101, an AAV9-mediated candidate gene regulation therapy, for the treatment of SCN1A+ Dravet syndrome (DS). The company plans to initiate the phase 1/2 clinical trial ENDEAVOR (NCT05419492), a 2-part dose escalation study in US, to assess the therapy in patients between the ages of 6 months to 3 years with SCN1A+ DS in the first half of 2024.¹

In Part 1 of ENDEAVOR, investigators will evaluate up to 2 doses of ETX101 in 4 participants to assess the safety and tolerability of the agent, exploring preliminary efficacy and therapeutic dose selection. The first part is expected to start in the first half of 2024 and Part 2 is planned following demonstration of safety and efficacy in Part 1, a design the company aligned with the agency on for the trial. The gene therapy is designed to selectively upregulate expression of the SCN1A gene in GABAergic inhibitory interneurons and potentially address the underlying cause of the condition.

“I was very excited to hear this program will be able to get started in the US as it is a novel approach and includes the youngest patients with DS. There is still a huge unmet need for all aspects of the syndrome. While the newly approved antiseizure medications have really helped many patients reduce their seizure frequency the majority still continue to have seizures and we are really striving for as close to seizure freedom as possible,” principal investigator Joseph Sullivan, MD, director of the Pediatric Epilepsy Center at UCSF, told NeurologyLive.

FDA Grants Priority Review to Efficacy Supplement for Sarepta Therapeutics’ SRP-9001 Indication Expansion

A week later, on February 16, the FDA accepted and filed Sarepta Therapeutics’ efficacy supplement to the biologics license application (BLA) for the approved gene therapy SRP-9001 (Elevidys) for the treatment of ambulatory patients with Duchenne muscular dystrophy (DMD). The agency has granted the efficacy supplement a priority review with a review goal date of June 21, 2024, and has also confirmed no plan to hold an advisory committee meeting to discuss the supplement.²

The goals of the efficacy supplement include expanding the labeled indication for SRP-9001 as a treatment for patients with DMD who have a confirmed mutation in the DMD gene. In the statement, the company also noted the supplement will include converting the SRP-9001 accelerated approval—granted by the FDA last June—to a traditional approval.

"Appreciation for the FDA and their engagement throughout this process – they have moved quickly to provide us with guidance and in granting priority review. The target review date of June 21 speaks to their commitment to urgency in considering the evidence included in the supplement that supports treatment with SRP-9001," Louise Rodino-Klapac, PhD, chief scientific officer and executive vice president of R&D at Sarepta, told NeurologyLive. "Happy and hopeful for patients and families – the totality of evidence that we have seen in our clinical program supports the conclusion that SRP-9001 is modifying the trajectory of Duchenne and today’s news brings us one step closer to having this treatment available to as many individuals with Duchenne as possible."

Eplontersen Gains FDA Fast Track Designation for Transthyretin-Mediated Amyloid Cardiomyopathy

Months after the FDA approved Ionis’ eplontersen (Wainua) as a treatment for polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN), on February 26, the FDA granted fast track designation for an extended indication to treat adults with ATTR cardiomyopathy (ATTR-CM). The therapy is currently being assessed in the global, phase 3 CARDIO-TTRansform study (NCT04136171), a 1400-patient cohort trial that’s considered the largest of ATTR-CM to date.³

CARDIO-TTRansform, a multicenter, double-blind study, will randomize patients to receive subcutaneous injections of either eplontersen or placebo once every 4 weeks for up to 140 weeks. Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A. The primary outcome is the composite outcome of cardiovascular (CV), mortality, and recurrent CV clinical events up to 140 weeks while secondary outcomes include change in 6-minute walk test (6MWT) distance and change in Kansas City Cardiomyopathy Questionnaire scores at week 121.

"Receiving Fast Track designation from the FDA reinforces our belief that eplontersen has the potential to be a transformational treatment for patients with ATTR-CM, which remains a progressive and fatal condition for hundreds of thousands of people worldwide despite available treatment options,” Eugene Schneider, MD, executive vice president and chief medical development officer at Ionis, said in a statement.³ "CARDIO-TTRansform is the largest, most comprehensive study ever conducted in ATTR-CM patients, with results expected as early as next year."

REFERENCES
1. Encoded Therapeutics Announces US IND Clearance and Australian CTA Approval for Dravet Syndrome Gene Therapy Candidate ETX101. News Release. Encoded Therapeutics. Published February 6, 2024. Accessed March 8, 2024. https://encoded.com/press-releases/encoded-therapeutics-announces-us-ind-clearance-and-australian-cta-approval-for-dravet-syndrome-gene-therapy-candidate-etx101/
2. Sarepta Therapeutics Announces U.S. FDA Acceptance of an Efficacy Supplement to Expand the ELEVIDYS Indication. News Release. Sarepta Therapeutics. Published February 16, 2024. Accessed March 8, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-us-fda-acceptance-efficacy
3. Eplontersen granted US fast track designation for patients with transthyretin-mediated amyloid cardiomyopathy. News release. Ionis. February 8, 2024. Accessed March 8, 2024. https://ir.ionispharma.com/news-releases/news-release-details/eplontersen-granted-us-fda-fast-track-designation-patients