Blocks lifted, requests and approvals

The FDA took a handful of actions in September 2022, including a new approval for amyotrophic lateral sclerosis (ALS), application acceptance in Huntington’s disease (HD), and a few others.

With all treatments advancing through the clinical development pipeline, the NeurologyLive® The team has worked hard to cover all the moves of the agency to make sure you are up to date with the latest neurology news. To give you a chance to catch up on any headlines you may have missed over the past month, we’ve compiled all the updates in one place. Coverage includes the latest FDA approvals, new designations, submissions and resubmissions, as well as clinical trial initiations and suspensions.

Click the Read More buttons for more details and information on each update.

Hold lifted on phase 2 trial of SRP-5051 in DMD likely to skip exon 51

On September 6, the FDA lifted its clinical hold on Part B of the Phase 2 MOMENTUM trial (NCT04004065) evaluating Sarepta Therapeutics’ SRP-5051, an investigational treatment for patients with Duchenne muscular dystrophy (DMD). likely to skip exon 51.1

The hold was initially placed on the trial in June 2022, after reports that a patient experienced a serious adverse event (SAE) after being treated with high dose SRP-5051. The patient in question presented with grade 3 hypomagnesemia, grade 4 potassium deficiency, muscle cramps and mild to moderate tingling in the extremities. As a result of this waiver, Sarepta will need to adjust its global trial protocol to include expanded urinary biomarker monitoring as part of the risk mitigation and safety monitoring plan.

“We would like to thank the FDA for working closely with us to quickly resolve this clinical blockage. We will implement protocol changes to resume dosing in the United States as soon as possible,” said Louise Rodino- Klapac, PhD, executive vice president and chief scientific officer of Sarepta Therapeutics, in a statement, “Our monitoring plan is designed to mitigate the risks of hypomagnesemia. MOMENTUM has continued to enroll participants outside of the United States, and we remain on track to complete enrollment by the end of 2022.”

Philips Respironics recalls masks for BPAP and CPAP machines after safety concerns

Also on September 6, the FDA announced that Philips Respironics had initiated a recall of several of its masks used with bilevel positive airway pressure (BPAP) and continuous positive airway pressure (CPAP) devices due to a serious security issue.2.3

Specifically, the recalled masks are intended for patients weighing more than 66 pounds, with the exception of the Wisp Youth Nasal Mask and 3100 NC/SP Therapeutic Mask, which are intended for patients 7 years of age and older weighing more than 40 pounds. The recalled masks, which included the Amara View full face mask, DreamWisp nasal mask, Wisp and Wisp Youth nasal masks and 3100 NC/SP therapy mask, each have magnetic clips to hold them in place. In the FDA report, it was noted that these magnets can cause potential injury or death, as well as interfere with certain metal medical devices and metal objects in the body.

Wearers of pacemakers, implantable cardioverter defibrillators, metal stents, neurostimulators, magnetic metal implants, cerebrospinal fluid (CSF) shunts and aneurysm clips may be potentially at risk with these recalled masks. The agency also announced that there are several other metallic medical devices or objects that pose a potential risk, including intracranial aneurysm intravascular flow-disrupting devices, eye implants, certain metal contact lenses, brackets magnets for dental prostheses, implantable orifices and pumps, etc.

The modified LIFT-AD study to evaluate fosgonimeton monotherapy in Alzheimer’s disease

Also on September 6, Athira Pharma announced that it was amending the ongoing LIFT-AD pivotal trial (NCT04488419) to evaluate its investigational agent fosgonimeton in patients with Alzheimer’s disease (AD) without acetylcholinesterase inhibitors. (AChEI) background, as the therapy has already shown promise as a monotherapy.4

According to the update, an independent, unblinded interim analysis will be performed to inform the required sample size needed to appropriately populate the primary endpoint target patient population. LIFT-AD is a double-blind, placebo-controlled, parallel-group study. Its results are measured by the Global Statistical Test. The study has enrolled over 300 patients with mild to moderate AD in the United States to date, and enrollment is still ongoing.

“We look forward to advancing the clinical evaluation of fosgonimeton so as to best determine its potential for patients with Alzheimer’s disease while preserving the integrity of the LIFT-AD study and maximizing its chances of success,” said Hans Moebius, MD, PhD, director. “Our decision to focus LIFT-AD on fosgonimeton therapy without background cholinergics was guided by the results of the ACT-AD trial and a blinded analysis of the Importantly, fosgonimeton remains well tolerated, with a favorable safety profile in the overall study population.

FDA accepts NDA for trofinetide in Rett syndrome

Later that month, on September 12, the FDA accepted a New Drug Application (NDA) for trofinetide (formerly known as NNZ-2566), an investigational treatment for Rett syndrome developed by Acadia Pharmaceuticals. The agency has set an action date under the Prescription Drug User Fee Act of March 12, 2023 for review of the claim.5

Acadia’s announcement noted that the FDA had not requested an advisory committee meeting for trofinetide, which was granted fast-track status, as well as orphan drug designation, in 2015 for the treatment of Rett. In 2020, the treatment received rare pediatric disease designation. The NDA is supported by data from the Phase 3 LAVENDER study (NCT04181723), which evaluated the synthetic analog of the amino‐terminal tripeptide of IGF-1 in 187 girls and women with Rett syndrome.

“We are pleased that the FDA has accepted our NDA request and will work closely with them to facilitate the timely completion of the review,” said Steve Davis, CEO of Acadia Pharmaceuticals, in a statement. “If approved, trofinetide will be the first drug available for the treatment of Rett syndrome, a rare and devastating disease for patients and their families. This milestone reinforces Acadia’s ongoing commitment to advancing research into high unmet need in disorders affecting the central nervous system.

AMX0035 Approved for the treatment of ALS

Towards the end of the month, on September 29, the FDA approved AMX0035, a sodium phenylbutyrate-taurursodiol co-formulation developed by Amylyx Pharmaceuticals, for the treatment of ALS. The drug, which will be marketed as Relyvrio, has become the third treatment approved to help slow disease progression or mortality in ALS, following riluzole (Rilutek) in 1995 and edaravone (Radicava; MT Pharma) in 2017.6

The move came just weeks after the FDA’s Peripheral and Central Nervous System Drug Advisory Committee reconvened on the treatment and voted that current data was sufficient to demonstrate efficacy. The panel voted 7–2 (7 yes; 2 no) in favor of its recommendation for FDA approval.

“Today’s decision by the United States Food and Drug Administration to approve RELYVRIO for the treatment of ALS in adults is an exciting milestone for Amylyx, representing our first regulatory approval in the United States and our second regulatory approval around the world, and most importantly, the wider ALS community, including people living with ALS, their families, and clinicians,” said Josh Cohen and Justin Klee, co-founders and co-chief operating officers of Amylyx. , in a press release.

REFERENCES
1. Sarepta Therapeutics announces that the FDA has lifted its clinical hold on SRP-5051 for the treatment of Duchenne muscular dystrophy. Press release. Sarepta. September 6, 2022. Accessed October 3, 2022. https://www.globenewswire.com/news-release/2022/09/06/2510416/36419/en/Sarepta-Therapeutics-Announces-That-FDA-has-Lifted- his-clinical-expectation-on-SRP-5051-for-the-treatment-of-Duchenne-muscular-dystrophy.html
2. Certain Philips Respironics masks for BiPAP, CPAP devices recalled due to safety issue with magnets that may affect certain medical devices: FDA Safety Communication. Press release. FDA. September 6, 2022. Accessed October 3, 2022. https://www.fda.gov/medical-devices/safety-communications/certain-philips-respironics-masks-bipap-cpap-machines-recalled-due-safety-issue – magnets-can-affect
3. Philips Respironics is advising customers worldwide of updated instructions and labeling for specific sleep therapy masks that contain magnetic headgear clips due to the potential risk of serious injury. Press release. Philips Respironics. September 6, 2022. Accessed October 3, 2022. https://www.usa.philips.com/aw/about/news/archive/standard/news/press/2022/20220906-philips-respironics-alerts-customers-worldwide – updated-instructions-and-labeling-for-sleep-therapy-masks-containing-magnetic-attachments-due-to-the-potential-risk-of- serious-injury.html
4. Athira Pharma provides updates on plans for the ongoing LIFT-AD clinical study of fosgonimeton in patients with mild to moderate Alzheimer’s disease. Press release. Athira Pharma. September 6, 2022. Accessed October 3, 2022. https://www.globenewswire.com/news-release/2022/09/06/2510202/0/en/Athira-Pharma-Provides-Update-on-Plans-for- Ongoing-LIFT-AD-Clinical-Study-of-Fosgonimeton-in-Mild-to-Moderate-Alzheimer-s-Patients.html
5. Acadia Pharmaceuticals announces that the New Drug Application Trofinetide for the treatment of Rett Syndrome has been accepted for filing and review by the US FDA. Press release. Acadian Pharmaceuticals. September 12, 2022. Accessed October 3, 2022. https://acadia.com/media/news-releases/acadia-pharmaceuticals-announces-trofinetide-new-drug-application-for-the-treatment-of-rett-syndrome – has-been-accepted-for-filing-and-review-by-us-fda/

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