FDA Action Update, October 2024: Approvals, Acceptance, and Hold Removal

The FDA was busy in October 2024, making a number of decisions on potential new therapeutic agents including granting approvals, accepting a resubmitted new drug application, and removing a clinical hold.

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 Removes Partial Hold for Myotonic Dystrophy Agent AOC 1001

Early in the month, on October 3, the FDA removed a partial clinical hold on Avidity Biosciences’ investigational agent AOC 1001 in development for patients with myotonic dystrophy type 1 (DM1). The hold, originally placed in September 2022, was related to a serious adverse event reported in a single patient treated in the 40-mg arm of the phase 1/2 MARINA trial (NCT05027269).^1,2

At the time of the partial hold, nearly 40 of the anticipated 44 participants had been enrolled in MARINA and its open-label extension (OLE); however, all participants, whether on AOC 1001 or placebo, were instructed to continue dosing as planned. The company also noted that the clinical hold was not going to impact those who choose to enter the OLE.²

AOC 1001, otherwise known as delpacibart etedesiran (del-desiran), consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a siRNA targeting DMPK, the root cause of DM1. The agent is currently being investigated in the global phase 3 HARBOR trial (NCT05479981) and the ongoing MARINA-OLE trial.

FDA Approves Avadel's Sodium Oxybate for Cataplexy or Excessive Daytime Sleepiness in Pedatric Narcolepsy

A couple weeks later, on October 17, the FDA approved Avadel Pharamaceuticals' supplemental new drug application (sNDA) for sodium oxybate (Lumryz) for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. With this approval, sodium oxybate could reduce the burden on families and caregivers of pediatric patients with narcolepsy who must wake up at night to administer a second dose.³

“My initial reaction to the FDA's approval of Lumryz for pediatric use was one of immense pride. We have heard from many parents and caregivers of the challenges they’ve experienced with the twice-nightly dosing required of other oxybates and their interest in a once-nighty treatment option. Lumryz is a testament to our dedication to placing patients at the center of everything we do at Avadel and we’re proud to now serve children with narcolepsy and their families,” Greg Divis, Chief Executive Officer at Avadel Pharmaceuticals, told NeurologyLive^®.

In May 2023, the agency initially approved sodium oxybate for cataplexy or excessive daytime sleepiness in adults with narcolepsy after Avadel submitted an amendment to the FDA’s request for final approval.⁴ Lumryz comes with a boxed warning as a central nervous system depressant, and for its potential abuse and misuse. It is currently only available through a restricted program under a Risk Evaluation and Mitigation Strategy called the Lumryz REMS. With the approval, the drug was granted 7 years of orphan drug exclusivity.

FDA Approves AbbVie’s 24-Hour Foscarbidopa/Foslevodopa Pump for Advanced Parkinson Disease Treatment

On the same day, on October 17, the FDA approved AbbVie’s foscarbidopa/foslevodopa, marketed as Vyalev, as the first and only subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of motor fluctuations in adults with advanced Parkinson disease (PD). The company noted that timing for a patient's access to the therapy is dependent on their individual insurance plan, with coverage for Medicare patients expected in the second half of 2025.⁵

“Overall, there is great excitement around the approval of Vyalev. While there are numerous options for the symptomatic treatment of PD, the options become limited as the disease progresses, and patients experience motor fluctuations despite their current treatment," Pavnit Kukreja, PharmD, senior director, neuroscience, US Medical Affairs, AbbVie, told NeurologyLive. "Previously, only more invasive options, such as surgery, existed. Vyalev offers the ability to continuously deliver the gold standard, levodopa, without surgery, over the morning, day, and night."

The approval was supported by data from the phase 3 M15-736 study (NCT04380142) that assessed the efficacy of continuous subcutaneous infusion of foscarbidopa/foslevodopa, also known as ABBV-951, among adult patients with advanced PD compared with oral immediate-release carbidopa/levodopa (CD/LD IR), along with a 52-week, open-label M15-741 study (NCT03781167) which investigated the long-term safety and efficacy of the treatment. Results from the M15-736 study revealed that patients who received foscarbidopa/foslevodopa reported superior improvement in motor fluctuations, with increased ON time without troublesome dyskinesia and decreased OFF time, compared with oral CD/LD IR.

FDA Accepts Resubmitted NDA for Ataluren in Nonsense Duchenne Muscular Dystrophy

At the end of the month, on October 30, the FDA accepted PTC Therapeutics resubmitted new drug application (NDA) for its protein restoration therapy ataluren (Translarna) for the treatment of boys with nonsense mutation Duchenne muscular dystrophy (nmDMD). Because this was an NDA resubmission following a complete response letter (CRL) filed several years ago, the FDA is not obligated to follow PDUFA review timelines and thus, did not provide an action date for the therapy.⁶

The resubmitted NDA was based on data from a phase 3 placebo-controlled trial, dubbed Study 041 (NCT03179631), which included an intent-to-treat population of 359 patients with nmDMD. In addition, the resubmission also included analyses from the STRIDE registry, an ongoing, multicenter, observational study of the safety and effectiveness of ataluren in routine care. Currently, the therapy is licensed in multiple countries, including the European Union and Brazil.

"The NDA acceptance for review is a significant milestone that brings us one step closer to providing this important treatment to boys and young men living with nonsense mutation Duchenne muscular dystrophy in the United States,” Matthew B. Klein, MD, chief executive officer at PTC, said in a statement.⁶ "The totality of evidence clearly supports the favorable safety profile and short- and long-term benefits of Translarna for individuals with nmDMD. We look forward to working with FDA throughout the review process."

REFERENCES
1. Avidity Biosciences Announces FDA Removed Partial Clinical Hold on Delpacibart Etedesiran (del-desiran/AOC 1001). News release. Avidity Biosciences. October 3, 2024. Accessed November 8, 2024. https://aviditybiosciences.investorroom.com/2024-10-03-Avidity-Biosciences-Announces-FDA-Removed-Partial-Clinical-Hold-on-Delpacibart-Etedesiran-del-desiran-AOC-1001
2. Avidity Biosciences announces FDA partial clinical hold on new participant enrollment in phase 1/2 MARINA trial. News release. September 27, 2022. Accessed November 8, 2024. https://aviditybiosciences.investorroom.com/2022-09-27-Avidity-Biosciences-Announces-FDA-Partial-Clinical-Hold-on-New-Participant-Enrollment-in-Phase-1-2-MARINA-TM-Trial
3. Avadel Pharmaceuticals Announces FDA Approval of LUMRYZ™ (sodium oxybate) Extended-Release Oral Suspension (CIII) for the Treatment of Cataplexy or Excessive Daytime Sleepiness in Patients 7 Years of Age and Older with Narcolepsy. News Release. Avadel Pharmaceuticals. Published October 17, 2024. Accessed November 8, 2024. https://investors.avadel.com/news-releases/news-release-details/avadel-pharmaceuticals-announces-fda-approval-lumryztm-sodium
4. Avadel Pharmaceuticals announces final FDA approval of Lumryz (sodium oxybate) for extended-release oral suspension as the first and only once-at-bedtime oxybate for cataplexy or excessive daytime sleepiness in adults with narcolepsy. News release. Avadel Pharmaceuticals. May 1, 2023. Accessed November 8, 2024. https://www.globenewswire.com/news-release/2023/05/01/2658536/0/en/Avadel-Pharmaceuticals-Announces-Final-FDA-Approval-of-LUMRYZ-sodium-oxybate-for-Extended-Release-Oral-Suspension-as-the-First-and-Only-Once-at-Bedtime-Oxybate-for-Cataplexy-or-Exc.html
5. U.S. FDA Approves VYALEV™ (foscarbidopa and foslevodopa) for Adults Living with Advanced Parkinson's Disease. News Release. AbbVie. Published October 17, 2024. Accessed November 8, 2024. https://news.abbvie.com/2024-10-17-U-S-FDA-Approves-VYALEV-TM-foscarbidopa-and-foslevodopa-for-Adults-Living-with-Advanced-Parkinsons-Disease
6. PTC Therapeutics announces FDA acceptance of Translarna NDA resubmission. News release. PTC Therapeutics. October 30, 2024. Accessed November 8, 2024. https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-fda-acceptance-translarnatm-nda