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FDA Action Update, November 2021: Clearances, Approvals, and Submissions

Catch up on any of the neurology news headlines you may have missed over the course of the last month, compiled all into one place by the NeurologyLive® team.

A number of FDA actions took place in November 2021, including application submissions for a hopeful therapy for amyotrophic lateral sclerosis (ALS), an application clearance and approvals in epilepsy, and 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.

Click the read more buttons for more detail and information about each update.

Amylyx Submits NDA for ALS Treatment AMX0035

Early in November, Amylyx Pharmaceuticals submitted a new drug application (NDA) to the FDA for its investigational treatment, AMX0035, for the treatment of patients with amyotrophic lateral sclerosis (ALS).1 The NDA is supported by data from the phase 2/3 CENTAUR trial (NCT03127514), in which the agent (n = 87) met its primary efficacy end point, with a reported average ALS Functional Rating Scale-Revised (ALSFRS-R) score of 2.32 points higher than placebo (n = 48; = .03) after 24 weeks of treatment.2 Those in the study were randomized 2:1 to either active treatment or placebo.

Additional data showed that from baseline, there was a 2.92-point higher mean ALSFRS-R score for the AMX0035 group (= .01) and a –1.24 points per month change in total ALSFRS-R score compared to –1.66 points per month with placebo (difference, 0.42 points per month [95% CI, 0.03-0.81]; = .03).2

"We are excited to share with the ALS community the exciting milestone that we have submitted our NDA to the FDA for review," Justin Klee, Co-CEO, director and co-founder, Amylyx, said in a statement at the time, with Joshua Cohen, Co-CEO, chairman and co-founder, Amylyx, adding that "our team has worked and continues to work around the clock as we know time is of the essence for people living with ALS and their families. We will continue to keep the community closely updated on our progress.”1

Cerezen Device Given Breakthrough Designation for MCI and Alzheimer Disease

Shortly after the Amylyx news, an announcement came from Renew Biosciences that the FDA had granted a breakthrough device designation to its Cerezen Device for the treatment of mild cognitive impairment (MCI) due to Alzheimer disease (AD) and for mild AD dementia.3

The nonpharmacologic and noninvasive device was designed to improve cerebrovascular health through the enhancement of circulation, and the simulation of vigorous exercise’s physiological effects and endothelial cell function. The pathology of AD has long been associated with cerebrovascular risk factors, with Renew citing the role that cerebral blood flow and endothelial function are believed to play.

Tony Robinson, chief operating officer, Renew Bioscience, said in a statement that the company was "extremely pleased with the progress” the Cerezen Device had made as it journeys through the pipeline, adding that “we truly believe that Cerezen represents a momentous potential advancement in the treatment of Alzheimer's and dementia.” The company shared data from its recently completed pivotal study at the 2021 Clinical Trials on Alzheimer's Disease (CTAD) Conference.

Focal Epilepsy Agent NRTX-1001 Gets IND Clearance

As November rolled along, Neurona Therapeutics announced that its inhibitory nerve cell therapy derived from human pluripotent stem cells, NRTX-1001, received an investigational new drug (IND) clearance by the FDA, allowing the company to proceed with its first-in-human phase 1/2 clinical trial in patients with drug-resistant mesial temporal lobe epilepsy (MTLE).4

The multicenter trial will evaluate the safety, tolerability, and efficacy of single-administration NRTX-1001 in 2 stages. The first is an open-label dose-escalation study with up to 10 participants with MTLE included, while the second stage is a randomized, blinded investigation comparing the safety and efficacy of the cell therapy to a control group in a cohort of 30 people with MTLE. Delivered as a 1-time dose, NRTX-1001 is designed to secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), providing long-term GABAergic inhibition to repair hyperexcitable neural networks that underlie epilepsy and other central nervous system disorders.

"The clearance of our first IND is a key milestone for Neurona and a testament to the talent, experience, and hard work of the entire Neurona team," Cory Nicholas, PhD, president and chief executive officer, Neurona, said in a statement.4 "This milestone is especially rewarding and timely given that November is Epilepsy Awareness Month. Epilepsy is one of the most common neurological disorders, affecting over 3 million people in the US, of whom approximately one-third have drug-resistant disease. NRTX-1001 is a new type of inhibitory cell therapy that is targeted to the focal seizure onset region in the brain and, in a single treatment, has the potential to significantly improve the lives of people living with focal epilepsy.”

First Oral Solution of Topiramate for Epilepsy and Migraine Approved

The day after Neurona’s announcement, Azurity Pharmaceuticals released the confirmation that the FDA had approved its oral formulation of topiramate 25 mg/mL (Eprontia) for the treatment of epilepsy and migraine, making it the first and only liquid formulation of topiramate to be greenlit by the agency.5

Topiramate was originally approved under the brand name Topamax in 1996 as a carbonic anhydrase inhibitor medication to treat epilepsy and prevent migraines. In addition to the number of several indications it has, the therapy is also used to treat medication overuse headache and was recommended by the European Federation of Neurological Societies as one of the few medications showing effectiveness for this indication.6

This Azurity formulation can now be used orally as a monotherapy to treat partial-onset or primary generalized tonic-clonic seizures in patients 2 years of age and older, as an adjunctive therapy for treatment of partial-onset seizures, primary generalized tonic-clonic seizures or seizures associated with Lennox-Gastaut syndrome in the same age group, and as a preventive treatment of migraine for patients aged 12 years and older.

"Our ability to address each patient’s needs, with a tailored approach and a proven therapy, is transformative for patients, caregivers, and the healthcare professionals who treat them. Eprontia’s ready-to-use liquid formulation provides HCPs a therapy that addresses an unmet medical need,” Amit Patel, chairman and chief executive officer, Azurity Pharmaceuticals, said in a statement.5

NeuroPace RNS System Gets IDE for Study in Idiopathic Generalized Epilepsy

In mid-November, the FDA granted an investigational device exemption (IDE) to NeuroPace for its responsive neurostimulation (RNS) system to be evaluated in patients with drug-resistant idiopathic generalized epilepsy (IGE).6 The RNS System was originally approved in 2013 for the treatment of medical refractory epilepsy and acts on closed-looped technology that monitors and responds to a patient’s unique brain patterns to deliver therapy in real-time prior to symptom onset.7

The news comes just a few months after the company announced it had been granted breakthrough device designation status from the FDA for the treatment of IGE. NeuroPace has yet to announce further details of the upmcoming study, including primary and secondary end points. Dubbed NAUTILUS, the prospective, single-blind, multicenter, randomized pivotal study will be the first to evaluate the effects of brain-responsive neuromodulation in this patient population. Enrollment is expected to begin in 2022.

"We are pleased with FDA’s decision to grant IDE approval for the pivotal study, allowing us to evaluate the safety and effectiveness of the RNS System in patients who are living with drug-resistant, idiopathic generalized epilepsy," Martha Morrell, MD, chief medical officer, NeuroPace, said in a statement.7 "We look forward to working closely with the study investigators to evaluate a new treatment option that could potentially improve quality of life for these individuals in a meaningful way."

REFERENCES
1. Amylyx Pharmaceuticals submits new drug application (NDA) for AMX0035 for the treatment of ALS. News release. Amylyx Pharmaceuticals. November 2, 2021. Accessed December 2, 2021. https://www.businesswire.com/news/home/20211102005320/en/Amylyx-Pharmaceuticals-Submits-New-Drug-Application-NDA-for-AMX0035-for-the-Treatment-of-ALS
2. Paganoni S, Macklin EA, Hendrix S, et al. Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis. N Engl J Med. 2020;383:919-930. doi:10.1056/NEJMoa1916945
3. FDA grants Breakthrough status for Alzheimer's treatment. News release. Renew Biosciences. November 2, 2021. Accessed December 2, 2021. https://www.prnewswire.com/news-releases/fda-grants-breakthrough-status-for-alzheimers-treatment-301412262.html
4. Neurona Therapeutics receives IND clearance to initiate phase 1/2 clinical trial of neural cell therapy NRTX-1001 in chronic focal epilepsy patients. News release. Neurona Therapeutics. November 4, 2021. Accessed December 2, 2021. https://www.globenewswire.com/en/news-release/2021/11/04/2327414/0/en/Neurona-Therapeutics-Receives-IND-Clearance-to-Initiate-Phase-1-2-Clinical-Trial-of-Neural-Cell-Therapy-NRTX-1001-in-Chronic-Focal-Epilepsy-Patients.html
5. Azurity Pharmaceuticals announces FDA approval of Eprontia (topiramate) oral solution. News release. Azurity Pharmaceuticals. November 8, 2021. Accessed December 2, 2021. https://azurity.com/azurity-pharmaceuticals-inc-announces-fda-approval-of-eprontia-topiramate-oral-solution/
6. Evers S, Jensen R. Treatment of medication overuse headache – guideline of the EFNS headache panel. Eur J Neurol. 2021;18(9): 1115-1121. doi:10.1111/j.1468-1331.2011.03497.x
7. NeuroPace receives IDE approval to initiate NAUTILUS pivotal study of its RNS System for idiopathic generalized epilepsy. News release. November 10, 2021. Accessed December 2, 2021. https://www.globenewswire.com/news-release/2021/11/10/2331968/0/en/NeuroPace-Receives-IDE-Approval-to-Initiate-NAUTILUS-Pivotal-Study-of-its-RNS-System-for-Idiopathic-Generalized-Epilepsy.html