FDA Action Update, June 2024: Approvals, Designation, and Clearance

The FDA was busy in June 2024, making a number of decisions on potential new therapeutic agents including granting approvals, a designation, a clearance, an acceptance of application, a recommendation, and issuing a complete response letter.

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 Grants Regenerative Medicine Advanced Therapy Designation for AMT-130 Gene Therapy in Huntington Disease

Early in the month, on June 3, the FDA granted regenerative medicine advanced therapy (RMAT) designation to uniQure’s investigational Huntington disease (HD) gene therapy AMT-130 based on interim data from a phase 1/2 trial (NCT04120493) and a comparison analysis of the data to a nonconcurrent criteria-matched natural history cohort.¹ The company anticipates to provide an update of the interim data from the ongoing U.S. and European phase 1/2 studies investigating the agent in mid-2024, which will include up to 3 years of follow-up on 29 treated patients.

In December 2023, 30-month interim data from such trials showed evidence of potential dose-dependent clinical benefit relative to the nonconcurrent criteria-matched natural history.² Among 39 patients in the both trials, treatment with AMT-130 resulted in a 0.39-point difference on composite Unified Huntington’s Disease Rating Scale (cUHDRS) at 30 months and a 1.24-point difference at 18 months for the low- and high-dose groups, respectively (baseline values; low-dose, 14.1; high-dose, 14.9).

“We’re thrilled to receive the first ever RMAT designation for an investigational therapy for Huntington’s disease,” Matt Kapusta, MBA, chief executive officer at uniQure, said in a statement.¹ “This achievement is a significant milestone for the program and supports the potential for AMT-130 to address the high unmet medical need of those suffering from this devastating disease.”

FDA Clears Zeto’s Adjustable ONE Headset for EEG Brain Monitoring

A couple of days later, on June 4, the FDA granted 510(k) clearance for Zeto’s innovative next-generation product named ONE, a headset device that is equipped with 21 soft-tip electrodes positioned according to the commonly known 10-20 electroencephalography (EEG) system, according to a recent announcement. The company noted that the product, which is accompanied by intuitive LED feedback for any needed adjustment of the electrodes, requires minimal instruction for clinicians to use the device with their patients effectively.³

For clinicians who choose to use the portable device in their clinical practice, it can record video and audio from the patient while also providing a display for step-by-step guidance and recording controls. The headset device also offers clinicians the feature of live artificial intelligence (AI)-enabled notifications to alert them of seizure activity, which may be important when patients experience a status of critical condition or have an emergency event. The company noted that the device is approved for EEG brain monitoring across hospital, home, ambulance, and air transport environments.

"Zeto ONE is a breakthrough EEG system, revolutionizing many aspects of emergency EEG acquisition. We know that up to 40% of brain–injured emergency department and intensive care patients may experience seizures, which are often subclinical and require EEG for diagnosis,” Susan Herman, MD, professor and vice chair of clinical affairs in the department of neurology at Barrow Neurological Institute, said in a statement.³ “ONE fills a gap for hospitals that lack EEG resources—[it] provides streamlined point-of care application of full 10-20 electrodes, video and audio recording, AI triage tools, and efficient connectivity to the interpreting neurologist. This enhanced workflow ensures that EEGs have high technical quality and accurate interpretations in our most critically ill patients."

FDA Accepts Eisai’s sBLA for New IV Maintenance Dosing of Lecanemab

Slightly more than 2 months after it was submitted, on June 9, the FDA accepted Eisai’s supplemental biologics license application (sBLA) for a new monthly intravenous (IV) maintenance dosing of lecanemab-irmb (Leqembi), its approved medication for early-stage Alzheimer disease (AD). As a result, the agency has set a PDUFA action date for January 25, 2025, to give a final answer.⁴

According to the company, those who complete the biweekly IV initiation phase would still receive a monthly IV dose that maintains effective drug concentration to sustain the clearance of highly toxic protofibrils which can continue to cause neuronal injury. In addition, Eisai noted that it has initiated a rolling submission of a BLA to the FDA for a subcutaneous autoinjector version of lecanemab that allows maintenance dosing of the antiamyloid therapy. For context, the autoinjector gained fast track designation by the agency earlier this year in May.⁵

Lecanemab, which gained traditional approval in July 2023, was greenlit as a 100 mg/mL injection for patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. The newly accepted sBLA was based on modeling of observed data from the phase 2 study (Study 201; NCT01767311) and its open-label extension (OLE), as well as the phase 3 Clarity AD trial (Study 301; NCT03887455), and its OLE study. Lecanemab originally was approved under accelerated approval pathway using Study 201, and was later granted traditional approval based on data from Study 301, the confirmatory trial.

FDA AdComm Recommends Antiamyloid Therapy Donanemab as New Treatment for Alzheimer Disease

One day later, on June 10, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted that the data from the phase 3 TRAILBLAZER-ALZ-2 trial (NCT04437511) assessing donanemab (Eli Lilly), an investigational agent in development for AD, was sufficient enough in demonstrating clinical benefit. In the coming weeks, the agency will give its final decision as to whether the therapy will be approved.⁶

At the conclusion of the hearing, the committee voted 11-0 (11 Yes; 0 No; 0 Abstain) that the evidence presented showed that donanemab is effective for the treatment of AD in the population enrolled in clinical trials with mild cognitive impairment (MCI) and mild dementia. In determining the vote, the committee members also factored in whether there was efficacy across the entire population, or in just a subset of patients (e.g., those with low, medium, and high tau levels).

"Extremely positive," Martin J. Sadowski, MD, PhD, a professor of neurology, psychiatry, and pharmacology at the NYU Grossman School of Medicine and director of the NYU Alzheimer Drug Trial Program, told NeurologyLive^® when asked to share his reaction. "The 11:0 vote of the advisory panel represents a solidifying consensus among neurologists that anti-Aß antibodies are a valid disease-modifying strategy for treating patients with AD."

FDA Approves Cranbury’s Generic Version of Deflazacort to Treat Duchenne Muscular Dystrophy

A couple of days later, on June 12, the FDA approved a new generic version of deflazacort (Emflaza; PTC Therapeutics), a treatment indicated for patients 5 years of age and older with Duchenne muscular dystrophy (DMD). The new generic, which allows for greater access and improved cost-effectiveness, is from Cranbury Pharmaceuticals, a wholly-owned subsidiary of Tris Pharma.⁷

Deflazacort oral suspension, a corticosteroid indicated for DMD, has been on the market since 2017 under the name Emflaza and manufactured by PTC Therapeutics. It has several noted warnings and precautions, including alterations in endocrine function, immunosuppression and increased risk of infection, alterations in cardiovascular/renal function, gastrointestinal perforation, behavioral and mood disturbances, and effects on bones, among others. It is contraindicated in patients with known hypersensitivity to deflazacort or to any of the inactive ingredients.

"We were pleased to see a generic option for deflazacort, which has been available for much longer in Europe at generic prices. As corticosteroids like deflazacort represent standard-of-care for Duchenne, the wider availability of deflazacort will provide options for some families who may have previously had challenges getting the brand name version, Emflaza, approved," Sharon Hesterlee, PhD, executive vice president and chief research officer of the Muscular Dystrophy Association, told NeurologyLive^®.

FDA Grants Traditional Approval to Elevidys Gene Therapy for Ambulatory DMD, Accelerated Approval for Nonambulatory Patients

Months after the FDA accepted and filed Sarepta Therapeutics’ efficacy supplement to the biologics license application for SRP-9001 (Elevidys), on June 20, the agency granted it traditional approval for ambulatory patients with DMD. With traditional approval, SRP-9001's indication has been expanded to include patients aged 4 years and older with DMD who have a confirmed mutation in the DMD gene.⁸

The company announced that this agency decision also includes an accelerated approval for nonambulatory patients, continued approval for which may be contingent upon verification of clinical benefit in a confirmatory trial. The gene therapy, otherwise known as delandistrogene moxeparvovec-rokl, is contraindicated in patients with any deletion in exon 8 and/or exon 9.

“We are delighted that the FDA has expanded the label for Elevidys, Sarepta’s gene therapy for DMD to include ambulatory and non-ambulatory Duchenne patients who are older than 4 years of age," Debra Miller, founder and CEO of CureDuchenne, told NeurologyLive^®. "Families facing Duchenne have an urgent need for treatments that will delay the progression of the disease and this represents a significant treatment option for many boys and young men with Duchenne. We are grateful to Sarepta Therapeutics, the FDA, and of course the many families who have participated in clinical trials to advance this critical research."

FDA Approves Efgartigimod as New Treatment for Chronic Inflammatory Demyelinating Polyneuropathy

A day later, on June 21, the FDA approved Argenx's coformulation therapy efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) as a new treatment for adults with chronic inflammatory demyelinating polyneuropathy (CIDP). The therapy is the first and only neonatal Fc receptor (FcRn) blocker approved for the treatment of CIDP, and will be available as a once-weekly, 30- to 90-second subcutaneous injection.⁹

“Argenx continues to pursue our ambition to turn science into solutions for patients with severe autoimmunity,” Luc Truyen MD, PhD, the chief medical officer of argenx, said in a statement.⁹ “Patients have been waiting, and today, argenx is delivering the first innovative treatment for CIDP in more than 30 years. Vyvgart Hytrulo is a precision tool that has been shown to drive meaningful benefits for patients. Today’s FDA approval means that CIDP patients have a transformational new treatment option and further affirms the therapeutic profile of Vyvgart Hytrulo and the potential of FcRn blockade in IgG-mediated autoimmune diseases.”

The therapy was approved based on data from the pivotal phase 3 ADHERE study (NCT04281472) in which treatment with the agent significantly reduced relapse risk compared with placebo. All told, patients treated with Vyvgart Hytrulo had a 61% attenuated risk relative to placebo (P = .00039), with a safety profile that was consistent with previous studies.¹⁰

FDA Approves Pitolisant for Excessive Daytime Sleepiness in Pediatric Narcolepsy

Months after being granted priority review designation by the FDA, on June 24, the agency granted approval to Harmony Biosciences' pitolisant (Wakix), a selective histamine H3 receptor inverse agonist, for the treatment of excessive daytime sleepiness (EDS) in pediatric patients aged 6 years and older with narcolepsy. In addition, the agency issued pitolisant a complete response for the treatment of cataplexy in pediatric patients with narcolepsy.¹¹

Pitolisant's supplemental new drug application was supported by findings from a phase 3 trial (NCT02611687), which demonstrated significant reductions in EDS and cataplexy in pediatric patients aged 6 to 17 years with narcolepsy treated with 5 mg to 40 mg a day of the therapy. These findings suggested that pitolisant is a safe and effective treatment for children and adolescents with narcolepsy.¹²

"Following the FDA's decision to grant priority review, we are very pleased with the agency's timely review and approval of Wakix for pediatric narcolepsy patients with EDS," Jeffrey M. Dayno, MD, president and chief executive officer at Harmony Biosciences, said in a statement.¹¹ "EDS is the primary symptom experienced by all patients with narcolepsy and this approval for Wakix, as the first-and-only FDA-approved non-scheduled treatment option for narcolepsy, makes this important treatment option available to pediatric patients 6 years and older living with narcolepsy." 

FDA Issues AbbVie Complete Response Letter for ABBV-951 in Parkinson Disease

A day later, on June 25, the FDA again issued a complete response letter (CRL) to AbbVie's new drug application (NDA) for ABBV-951 (foscarbidopa/foslevodopa) for the treatment of motor fluctuations in adults with advanced Parkinson disease (PD).¹³

In the CRL, the agency cited observations identified during inspection of a third-party manufacturer listed in the NDA. The inspection at the facility did not involve ABBV-951 or any of the company's medicine. The CRL did not identify any issues in terms of safety, efficacy, or labeling of ABBV-951, including the device. Furthermore, the letter did not request that the company perform additional efficacy and safety studies related to the drug or device-related testing.

"There remains a tremendous unmet need for treatment options for patients living with advanced PD in the United States," Roopal Thakkar, MD, senior vice president, chief medical officer, global therapeutics, AbbVie, said in a statement.¹³ "We are focused on working with the FDA to bring this important therapy to patients as soon as possible."

REFERENCES
1. uniQure Receives FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for Investigational Gene Therapy AMT-130 in Huntington’s Disease. News Release. Published June 3, 2023. Accessed June 11, 2024. https://www.globenewswire.com/news-release/2024/06/03/2892124/0/en/uniQure-Receives-FDA-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-for-Investigational-Gene-Therapy-AMT-130-in-Huntington-s-Disease.html
2. uniQure Announces Update on Phase I/II Clinical Trials of AMT-130 Gene Therapy for the Treatment of Huntington’s Disease. News Release. Published December 19, 2023. Accessed June 11, 2024. https://www.globenewswire.com/news-release/2023/12/19/2798425/0/en/uniQure-Announces-Update-on-Phase-I-II-Clinical-Trials-of-AMT-130-Gene-Therapy-for-the-Treatment-of-Huntington-s-Disease.html
3. Zeto obtains FDA 510(k) clearance for its groundbreaking next-generation EEG brain monitoring product, ONE. News Release. Zeto. Published June 4, 2024. Accessed June 6, 2024. https://www.prnewswire.com/news-releases/zeto-obtains-fda-510k-clearance-for-its-groundbreaking-next-generation-eeg-brain-monitoring-product-one-302162697.html
4. FDA Accepts Eisai's Filing of LEQEMBI® (lecanemab-irmb) Supplemental Biologics License Application for IV Maintenance Dosing for the Treatment of Early Alzheimer's Disease. Eisai. June 9, 2024. Accessed June 10, 2024. https://www.prnewswire.com/news-releases/fda-accepts-eisais-filing-of-leqembi-lecanemab-irmb-supplemental-biologics-license-application-for-iv-maintenance-dosing-for-the-treatment-of-early-alzheimers-disease-302167814.html
5. Eisai Initiates Rolling Biologics License Application to US FDA for LEQEMBI® (lecanemab-irmb) for Subcutaneous Maintenance Dosing for the Treatment of Early Alzheimer’s Disease Under the Fast Track Status. News release. May 15, 2024. Accessed June 10, 2024. https://www.eisai.com/news/2024/news202430.html
6. FDA Peripheral and Central Nervous System Drugs Advisory Committee (PCNS). https://www.youtube.com/live/LPdOPydM18E. June 10, 2024. Accessed June 10, 2024.
7. Cranbury Pharmaceuticals receives US FDA approval for first generic version of Emflaza oral suspension (deflazacort) for Duchenne muscular dystrophy. News release. June 12, 2024. Accessed June 12, 2024. https://www.trispharma.com/cranbury-pharmaceuticals-receives-u-s-fda-approval-for-first-generic-version-of-emflaza-oral-suspension-deflazacort-for-duchenne-muscular-dystrophy/
8. Sarepta Therapeutics Announces Expanded US FDA Approval of ELEVIDYS to Duchenne Muscular Dystrophy Patients Ages 4 and Above. News Release. Sarepta Therapeutics. Published June 20, 2024. Accessed June 20, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-expanded-us-fda-approval-elevidys?_ga=2.261745871.332981042.1718920455-330115727.1718920455
9. argenx Announces FDA Approval of VYVGART Hytrulo for Chronic Inflammatory Demyelinating Polyneuropathy. News release. Argenx. June 21, 2024. Accessed June 21, 2024. https://www.us.argenx.com/news/argenx-announces-fda-approval-vyvgart-hytrulo-chronic-inflammatory-demyelinating-polyneuropathy
10. Argenx reports positive topline data from ADHERE study of Vyvgart Hytrulo in patients with chronic inflammatory demyelinating polyneuropathy. News release. Argenx. July 17, 2023. Accessed July 19, 2024. https://www.globenewswire.com/news-release/2023/07/17/2705309/0/en/argenx-Reports-Positive-Topline-Data-from-ADHERE-Study-of-VYVGART-Hytrulo-in-Patients-with-Chronic-Inflammatory-Demyelinating-Polyneuropathy.html
11. Harmony Biosciences Receives U.S. Food and Drug Administration Approval for Wakix® (Pitolisant) in Pediatric Patients With Narcolepsy. News Release. Harmony Biosciences. Published June 24, 2024. Accessed June 24, 2024. http://ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-receives-us-food-and-drug-administration-0
12. Dauvilliers Y, Lecendreux M, Lammers GJ, et al. Safety and efficacy of pitolisant in children aged 6 years or older with narcolepsy with or without cataplexy: a double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2023;22(4):303-311. doi:10.1016/S1474-4422(23)00036-4
13. AbbVie Provides U.S. Regulatory Update on ABBV-951 (Foscarbidopa/Foslevodopa). News Release. Published June 25, 2024. Accessed June 25, 2024. https://news.abbvie.com/2024-06-25-AbbVie-Provides-U-S-Regulatory-Update-on-ABBV-951-Foscarbidopa-Foslevodopa