FDA Action Update, September 2022: Holds Lifted, Applications, and Approvals

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

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 detail and information about each update.

Hold Lifted on Phase 2 Trial of SRP-5051 in DMD Amenable to Exon 51 Skipping

On September 6, the FDA lifted its clinical hold on part B of the phase 2 MOMENTUM trial (NCT04004065) assessing Sarepta Therapeutics' SRP-5051, an investigational treatment for patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping.¹

The hold was originally 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 experienced grade 3 hypomagnesemia, grade 4 potassium deficiency, muscular cramps, and mild-to-moderate tingling of the extremities. As a result of this lift, Sarepta will need to adjust its global trial protocol to include expanded monitoring of urine biomarkers as part of the risk mitigation and safety monitoring plan.

“We would like to thank FDA for working closely with us to expeditiously resolve this clinical hold. We will implement the changes in the protocol to resume dosing in the US as quickly as possible,” Louise Rodino-Klapac, PhD, executive vice president and chief scientific officer, Sarepta Therapeutics, said in a statement. “Our monitoring plan is designed to mitigate the risks of hypomagnesemia. MOMENTUM has continued enrolling participants outside the US, 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 begun a recall of several of its masks used with bilevel positive airway pressure (BPAP) machines and continuous positive airway pressure (CPAP) machines because of a serious safety concern.^2,3

Specifically, the recalled masks are for patients weighing more than 66 lbs, except for the Wisp Youth Nasal Mask and Therapy Mask 3100 NC/SP, which are for patients 7 years and older weighing more than 40 lbs. The recalled masks, which included the Amara View Full Face Mask, DreamWisp Nasal Mask, Wisp and Wisp Youth Nasal Masks, and Therapy Mask 3100 NC/SP, each have magnetic headgear clips to hold them in place. In the FDA's report, it was noted that these magnets can cause potential injuries or death, as well as interfere with certain metallic medical devices and metallic objects in the body.

Those with pacemakers, implantable cardioverter defibrillators, metallic stents, neurostimulators, magnetic metallic implants, cerebrospinal fluid (CSF) shunts, and aneurysm clips may be at potential risk with these recalled masks. The agency also announced that there are several other metallic medical devices or objects that present a potential risk, including intracranial aneurysm intravascular flow disruption devices, ocular implants, certain contact lenses with metal, magnetic denture attachments, implantable ports and pumps, and others.

LIFT-AD Study Amended to Assess Fosgonimeton as Monotherapy in Alzheimer Disease

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

According to the update, an independent, unblinded interim analysis will be conducted to inform the required sample size needed to appropriately power the primary end point target patient population. LIFT-AD is a double-blind, placebo-controlled, parallel-group study. Its outcomes are measured by the Global Statistical Test. The study has enrolled more than 300 patients with mild-to-moderate AD in the US to date, with enrollment still ongoing.

"We look forward to advancing the clinical evaluation of fosgonimeton in a way that will best determine its potential for Alzheimer’s disease patients while preserving the integrity of the LIFT-AD study and optimizing its chances for success,” Hans Moebius, MD, PhD, chief medical officer, Athira, said in a statement. "Our decision to focus LIFT-AD on fosgonimeton treatment without background cholinergics was guided by results from the ACT-AD trial and a blinded analysis of the ongoing LIFT-AD study. Importantly, fosgonimeton remains well tolerated, with a favorable safety profile in the full study population.”

FDA Accepts NDA for Trofinetide in Rett Syndrome

Later in the 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 set a Prescription Drug User Fee Act action date of March 12, 2023, for the review of the application.⁵

The announcement from Acadia noted that the FDA did not request 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 syndrome. In 2020, the treatment was granted rare pediatric disease designation. The NDA is supported by data from the phase 3 LAVENDER study (NCT04181723), which assessed the synthetic analog of the amino‐terminal tripeptide of IGF-1 in 187 girls and women with Rett syndrome.

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

AMX0035 Approved for the Treatment of ALS

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

This decision came just a few short weeks after the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee reconvened about the treatment, and voted that current data were sufficient in demonstrating efficacy. The panel voted 7­­­–2 (7 yes; 2 no) in favor of recommending it for FDA approval.

"Today’s decision by the US 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 US and our second regulatory approval worldwide, and importantly, the broader ALS community, including people living with ALS, their families, and clinicians," Josh Cohen and Justin Klee, cofounders and cochief operating officers, Amylyx, said in a statement.

REFERENCES
1. Sarepta Therapeutics Announces That FDA has Lifted its Clinical Hold on SRP-5051 for the Treatment of Duchenne Muscular Dystrophy. News 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-its-Clinical-Hold-on-SRP-5051-for-the-Treatment-of-Duchenne-Muscular-Dystrophy.html
2. Certain Philips Respironics masks for BiPAP, CPAP machines recalled due to safety issue with magnets that may affect certain medical devices: FDA Safety Communication. News 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-may-affect
3. Philips Respironics alerts customers worldwide of updated instructions and labeling of specific sleep therapy masks that contain magnetic headgear clips due to potential risk of serious injury. News release. Philips Respironics. September 6, 2022. Accessed October 3, 2022. https://www.usa.philips.com/a-w/about/news/archive/standard/news/press/2022/20220906-philips-respironics-alerts-customers-worldwide-of-updated-instructions-and-labeling-of-specific-sleep-therapy-masks-that-contain-magnetic-headgear-clips-due-to-potential-risk-of-serious-injury.html
4. Athira Pharma provides updates on plans for ongoing LIFT-AD clinical study of fosgonimeton in mild-to-moderate Alzheimer’s patients. News 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 Trofinetide New Drug Application for the Treatment of Rett Syndrome has been Accepted for Filing and Review by U.S. FDA. News release. Acadia 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-u-s-fda/