FDA Action Update, November 2022: Application Acceptances and a Refusal to File


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.

The FDA took a handful of actions in November 2022, including a number of application submissions, a refusal to file, and clearance of a brain monitoring platform, among other decisions.

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.

Neurocrine Biosciences Submits sNDA for Valbenazine in the Treatment of Huntington Disease Chorea

On November 3, Neurocrine Biosciences announced data from the phase 3 KINECT-HD study (NCT04102579) of valbenazine (Ingrezza) at the 29th annual meeting of the Huntington Study Group, during which time the company’s chief medical officer, Eiry W. Roberts, MD, noted that the data, along with findings from the ongoing open-label KINECT-HD2 study (NCT04400331), are the basis for the supplemental new drug application (sNDA) for the therapy in the treatment of chorea associated with Huntington disease (HD).1

Previously, in May 2022, the company announced that valbenazine had received an orphan drug designation from the FDA. Topline data of the selective vesicular monoamine transporter 2 inhibitor from KINECT-HD were presented in December 2021, at which time Roberts said, "the positive results of the KINECT-HD study move us closer to bringing valbenazine as a potential treatment option to patients in the US living with chorea, one of the most common symptoms of Huntington disease."

The poster data showed that valbenazine, which is approved in the US for the treatment of tardive dyskinesia, met its primary end point. Ultimately, at week 12, the placebo-adjusted least-squares mean change with valbenazine was a reduction of 3.2 units on the Total Maximal Chorea score (P <.0001).

Neurocrine Biosciences Submits Supplemental NDA for Valbenazine in the Treatment of Huntington Disease Chorea

Neurosteer Single-Channel EEG Platform Cleared by FDA

A day later, on November 4, the FDA cleared Neurosteer's single-channel electroencephalogram (EEG) brain monitoring platform, allowing for the multipurpose system to be utilized in a wide variety of clinical settings.2

The platform, which Neurosteer calls “unobtrusive,” is able to be used for continuous brain monitoring to support critical intervention in the intensive care unit and during in-office visits for the detection of presymptomatic cognitive decline related to diseases such as Alzheimer disease, Parkinson disease, and dementia. The platform can also be used in clinical trials for pharmaceutical therapeutics, helping as a cost-effective and quick mass screening tool for those with neurodegenerative diseases.

Amitai Bickel, MD, surgeon and faculty of medicine, Western Galilee Hospital, Bar-Ilan University, in Safed, Israel, said in a statement that after several years of experience with the platform, "I've realized what an advantage it is to have a compact, easy-to-apply EEG brain monitor that can be used for real-time continuous monitoring. Neurosteer's innovative platform has the potential to revolutionize the standard of care in managing brain health.”

Neurosteer Single-Channel EEG Platform Cleared by FDA

FDA Refuses to File BrainStorm’s BLA for NurOwn Mesenchymal Cell ALS Therapy

Later in the month, on November 10, BrainStorm Cell Therapeutics announced that it had received a refusal to file letter from the FDA in response to its biologics license application (BLA) for NurOwn (autologous mesenchymal stromal cells secreting neurotrophic factors cells).3 The FDA indicated that the company can request a Type A meeting to discuss the content of the refusal to file letter.

Chaim Lebovits, chief executive officer, BrainStorm, said in a statement that although the company was disappointed, "we remain committed to NurOwn's advancement as a treatment for this devastating disease. The company intends to request a Type A meeting and looks forward to continued discussions with the FDA. We continue to believe that NurOwn's Phase 3 trial represents a significant contribution to ALS therapy and will continue to work tirelessly to address the needs of people living with ALS by advancing science and partnering with researchers around the world."

In March 2021, following a review of the pivotal phase 3 trial (NCT03280056), the agency concluded that the current level of data did not cross the threshold of substantial evidence to support a BLA. Original results showed that NurOwn did not meet its primary end point of statistical significance, as 33% and 28% of those on MSC-NTF and placebo, respectively, showed a change in disease progression of at least 1.25 points on ALS Functional Rating Scale (ALSFRS-R) after 28 weeks of treatment.

FDA Refuses to File BrainStorm’s BLA for NurOwn Mesenchymal ALS Therapy

FDA Accepts NDA for Parkinson Disease Treatment IPX203

One day later, on November 11, Amneal Pharmaceuticals announced that the FDA had accepted its NDA for IPX203, a novel, oral formulation of carbidopa/levodopa (CD/LD) extended-release capsules intended to treat patients with Parkinson disease (PD), with a scheduled a PDUFA date of June 30, 2023.4

The basis for IPX203’s submission was RISE-PD, a multicenter, randomized, double-blind, active-controlled, parallel-group trial (NCT03670953). With data published in Neurology earlier this year, the study consisted of a 3-week open-label dose adjustment phase, followed by a 4-week open-label conversion to IPX203, and a 13-week double-blind maintenance phase. A total of 506 individuals with PD aged 40 years and older were randomly assigned, and required to have at least 2.5 hours daily OFF time during waking hours.

"The FDA filing acceptance of IPX203 marks another important milestone for Amneal as we strive to improve the lives and care of people living with Parkinson’s disease” Gustavo Pesquin, chief commercial officer, Amneal Specialty, said in a statement. "We look forward to engaging in conversations with the FDA as we advance the application. We believe the data in our RISE-PD study supports the important benefit IPX203 can offer to this community by providing longer duration of symptom control with the benefit of fewer doses."

FDA Accepts NDA for Parkinson Disease Treatment IPX203

FDA Accepts NDA for Myasthenia Gravis Treatment Zilucoplan

Then, on November 14, the FDA accepted the NDA for UCB Pharma’s investigational, subcutaneously delivered agent zilucoplan in the treatment of adults with acetylcholine receptor antibody positive (AChR-Ab+) generalized myasthenia gravis (gMG).5

The NDA is supported by data from the pivotal phase 3 RAISE study (NCT04115293), in which treatment with the agent at doses of 0.3 mg/kg daily resulted in meaningful and statistically significant improvements in key gMG-specific outcomes relative to placebo after 12 weeks of treatment. All told, zilucoplan, a self-administered complement component 5 inhibitor, met its primary end point in Myasthenia Gravis Activities of Daily Living score at week 12, with placebo-corrected mean improvements of 2.09 points.

Charl van Zyl, executive vice president of Neurology Solutions, and head of EU/International Markers at UCB, said in a statement, "People living with gMG experience high treatment burden, on top of the debilitating impact of the condition, and there is a clear need for additional targeted treatments to support the gMG community. Our goal is to provide a solution that can help meet these needs and transform lives."

FDA Accepts NDA for Myasthenia Gravis Treatment Zilucoplan

Duchenne Gene Therapy SRP-9001 Wins Priority Review

At the very end of November, the FDA accepted and granted priority review to Sarepta Therapeutics’ BLA for SRP-9001, an investigative gene therapy for treating Duchenne muscular dystrophy (DMD), with a PDUFA date set for May 29, 2023.6 The BLA was submitted using the accelerated approval pathway in September 2022.

Developed in partnership with Roche, SRP-9001 is designed to express microdystrophin to combat the deleterious effects of the dysfunctional dystrophin produced in DMD. It has been granted fast track, rare pediatric, and orphan drug designations in the US as well as orphan drug status in the EU, Switzerland, and Japan.

"We are delighted to announce that the FDA has accepted Sarepta’s BLA for SRP-9001 for filing and priority review," Doug Ingram, president and chief executive officer at Sarepta Therapeutics, said in a statement. "Duchenne is a relentlessly degenerative and invariably fatal disease, robbing children of muscle and function hourly and daily. Our BLA submission for an accelerated approval, along with the FDA’s acceptance of that BLA for filing and review, is a tremendously important milestone in our effort to bring a potentially life-changing gene therapy to Duchenne patients as rapidly as possible and we look forward to working with the FDA through the review process."

Duchenne Gene Therapy SRP-9001 Wins Priority Review

1. Neurocrine Biosciences Presents Additional Phase 3 Data for KINECT-HD Study Evaluating Valbenazine for Chorea Associated with Huntington Disease at HSG 2022. News release. Neurocrine. November 3, 2022. Accessed December 10, 2022. https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-additional-phase-3-data-for-kinect-hd-study-evaluating-valbenazine-for-chorea-associated-with-huntington-disease-at-hsg-2022-301666869.html
2. Neurosteer Announces FDA Clearance of the Neurosteer EEG Brain Monitoring Platform. News release. Neurosteer. November 4, 2022. Accessed December 10, 2022. https://www.prnewswire.com/news-releases/neurosteer-announces-fda-clearance-of-the-neurosteer-eeg-brain-monitoring-platform-301668493.html
3. BrainStorm Cell Therapeutics receives refusal to file letter from FDA for its new biologics license application for NurOwn for the treatment of ALS. News release. November 10, 2022. Accessed December 10, 2022. https://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-receives-refusal-to-file-letter-from-fda-for-its-new-biologics-license-application-for-nurown-for-the-treatment-of-als-301673753.html
4. Amneal announces US FDA filing acceptance of new drug application for IPX203 for the treatment of Parkinson disease. News release. November 11, 2022. Accessed December 11, 2022. https://www.businesswire.com/news/home/20221109005842/en/Amneal-Announces-U.S.-FDA-Filing-Acceptance-of-New-Drug-Application-for-IPX203-for-the-Treatment-of-Parkinson%E2%80%99s-Disease
5. UCB announces US FDA acceptance of new drug application and EMA MAA validation for zilucoplan for the treatment of generalized myasthenia gravis in adult patients. News release. UCB Pharma. November 14, 2022. Accessed December 11, 2022. https://www.prnewswire.com/news-releases/ucb-announces-us-fda-acceptance-of-new-drug-application-and-ema-maa-validation-for-zilucoplan-for-the-treatment-of-generalized-myasthenia-gravis-in-adult-patients-301676223.html
6. Sarepta Therapeutics announces that U.S. FDA has accepted for filing and granted priority review for the biologics license application for SRP-9001, Sarepta’s gene therapy for the treatment of ambulant individuals with Duchenne muscular dystrophy. News release Sarepta Therapeutics. November 28, 2022. Accessed December 12, 2022. https://www.globenewswire.com/news-release/2022/11/28/2563009/0/en/Sarepta-Therapeutics-Announces-That-U-S-FDA-has-Accepted-for-Filing-and-Granted-Priority-Review-for-the-Biologics-License-Application-for-SRP-9001-Sarepta-s-Gene-Therapy-for-the-Tr.html
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