FDA Action Update, April 2024: Approvals, Clearance, and Complete Response Letter

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Catch up on any of the neurology news headlines you may have missed over the course of April 2024, compiled all into one place by the NeurologyLive® team.

The FDA was busy in April 2024, making a number of decisions on potential new therapeutic agents including granting approvals, a clearance, and a fast track designation, issuing a complete response letter, and agreeing to a new specialized protocol for a clinical trial.

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 Clears Abbott’s i-STAT Traumatic Brain Injury Whole Blood Test as Bedside Assessment

At the start of the month, on April 1, the FDA granted clearance for Abbott's i-STAT traumatic brain injury (TBI) cartridge test to be used to assess patients with suspected mild TBIs, known as concussions, at their bedside. This decision by the agency will enable testing to be performed in many new healthcare settings beyond hospital emergency departments, thus advancing the potential of testing for TBI outside traditional healthcare settings.1

The whole blood test, a portable instrument, evaluates patients aged 18 years and older who report a suspected mild TBI. Results from the test can assist in ruling out the need for a CT scan of the head and help with determining the next steps of care for the patient. The testing, which is done with whole blood samples, can take place at healthcare settings without a lab, accelerating the evaluation of head traumas. Abbott’s previous TBI tests were cleared only for use with plasma or serum which required samples to be sent to a lab for processing and testing.

“Clinicians should be aware that this blood test, performed on Abbott's portable i-STAT Alinity device, uses whole blood to assess patients suspected of having a TBI, or concussion. The fact that it delivers lab-quality results in just 15 minutes is critical,” Beth McQuiston, MD, RD, neurologist and medical director at Abbott, told NeurologyLive®. “This means that clinicians can have access to test results right at the patient's bedside, which is significant for urgent care clinics and other healthcare settings beyond the hospital ER. Importantly, the test is applicable for evaluating patients up to 24 hours after an injury.”

FDA Clears Abbott’s i-STAT Traumatic Brain Injury Whole Blood Test as Bedside Assessment

FDA Issues Complete Response Letter for Apomorphine Infusion Device SPN-830 in Parkinson Disease Treatment

A couple of days later, on April 8, the FDA issued a complete response letter (CRL) to Supernus Pharmaceuticals’ for its new drug application (NDA) on SPN-830, an apomorphine infusion device treatment for OFF episodes in patients with Parkinson disease (PD).2 The CRL indicated that the review cycle of the application is complete but it is not ready for approval in its current form.

In the CRL, the FDA cited 2 areas that require additional review or more information on SPN-830. The first area relates to product quality. Recently, the company submitted additional product quality data to the FDA but has not been reviewed yet. The other area relates to the master file for the infusion device, which is proprietary to the device manufacturer.

Supernus plans to discuss the provision of the requested information with the device manufacturer and the next steps required for resubmission of SPN-830's NDA. In February 2024, the agency completed a successful preapproval inspection of the device manufacturer’s facility, with no noted clinical safety or efficacy issues identified.

“We remain committed to bringing SPN-830 to the market as an important treatment option for PD patients who experience motor fluctuations associated with off episodes. We will work with the FDA to address the CRL and to successfully resubmit our SPN-830 NDA,” Jack Khattar, president and CEO of Supernus, said in a statement.2

FDA Issues Complete Response Letter for Apomorphine Infusion Device SPN-830 in Parkinson Disease Treatment

FDA Agrees to New Specialized Protocol for Phase 3b Study of ALS Agent NurOwn

A day later, on April 9, the FDA agreed on a new design for a phase 3b trial of BrainStorm Cell Therapeutics agent NurOwn in patients with amyotrophic lateral sclerosis (ALS) using a special protocol assessment (SPA). The phase 3b trial, a 2-part, multicenter study, is expected to commence in 2024 and address objectives that support a future biologics license application (BLA) in ALS.3

NurOwn, an investigational product, is a technology platform of autologous mesenchymal stromal cells secreting neurotrophic factors cells (MSC-NTF). Under the SPA agreement, the FDA validated the clinical trial protocol and statistical analysis of the planned phase 3b study. Also known as Study BCT-006-US, the trial will enroll 200 participants earlier in the course of their disease, having the onset of ALS symptoms, including limb weakness, within the prior 24 months.

"We are pleased to have reached an agreement with the FDA on key elements of the Phase 3b trial design that provides a potential path forward towards obtaining regulatory approval,” Chaim Lebovits, president and chief executive officer at BrainStorm, said in a statement.3 "We believe that having this SPA in place will help de-risk certain regulatory aspects of the NurOwn clinical program. BrainStorm's ultimate goal is to provide a new treatment option that can help patients afflicted with ALS, and we believe that the SPA potentially brings us one step closer to this goal. We appreciate the Agency's engagement and guidance during the SPA process and look forward to moving forward with the study."

FDA Agrees to New Specialized Protocol for Phase 3b Study of ALS Agent NurOwn

FDA Approves Alternate Administration Routes for Antiseizure Medication Cenobamate

A few more days later, on April 11, the FDA granted approval for 2 new administration options for SK Life Science’s cenobamate CV (Xcopri), a previously approved antiseizure medication (ASM) for adults with partial-onset seizures. The treatment tablets can now be crushed and mixed with water and either administered by mouth as an oral suspension or via a nasogastric tube, providing additional flexibility for dosing.4

This label update is supported by findings from an open-label, randomized, single-center, 3-period, 6-sequence, balanced crossover study that assessed the pharmacokinetics (PK) and safety of 3 cenobamate administration routes in 24 healthy participants (ages 18-50 years). Between all 3 administration routes, which included swallowing an intact tablet, as a crushed tablet suspended in water and taken orally, and as a crushed tablet suspended in water and administered via a nasogastric tube, investigators observed bioequivalence to the originally approved administration route (test-to-reference ratios for PK parameters [Cmax, AUClast, and AUC0-inf] 90% CIs, 80%-125%).5

"We were very pleased to see this information become part of the newly approved label for cenobamate CV. This is an important administration option for both patients and their caregivers who need an option when patients may not have the ability to swallow a whole tablet. We studied the administration of cenobamate CV in 2 methods: Crushing the tablet and mixing with a small amount water and swallowing it orally, or crushing the tablet, mixing it with water and administering it through a nasogastric tube. Both methods were shown to be equivalent to swallowing a whole tablet,” Louis Ferrari, RPh, MBA, vice president of medical affairs at SK Life Science, told NeurologyLive®.

FDA Approves Alternate Administration Routes for Antiseizure Medication Cenobamate

FDA Grants Fast Track Designation for Gene Therapy Candidate LX2006 in Friedreich Ataxia Cardiomyopathy

A few days later, on April 16, the FDA granted fast track designation to Lexeo Therapeutics’ LX2006, an adeno-associated virus (AAV) gene therapy candidate, for the treatment of Friedreich ataxia (FA) cardiomyopathy. LX2006, a therapy aimed to deliver a functional frataxin gene to promote frataxin protein expression and restore mitochondrial function in myocardial cells, received this designation based on available preclinical data.6

SUNRISE-FA (NCT05445323), an ongoing phase 1/2, dose-ascending, open-label trial, will assess the safety and tolerability, as well as preliminary efficacy, of LX2006 in patients with FA cardiomyopathy. In June 2023, the company announced the completion of patient dosing in the first cohort of the SUNRISE-FA and initial dosing of the first patient in the second cohort. SUNRISE-FA includes approximately 9 individuals with FA-associated cardiomyopathy who are followed for a 52-week period. Thus far, preliminary data from the first dose cohort indicated that the therapy was well tolerated, with no unexpected events or toxicities.

“FA cardiomyopathy is the leading cause of death among FA patients, and there are currently no approved treatment options. The FDA’s fast track designation for LX2006 underscores the significant unmet need for effective treatment options to address the cardiac impact of this debilitating disease,” R. Nolan Townsend, chief executive officer at Lexeo Therapeutics, said in a statement.6 “We believe today’s fast track designation, along with the previously announced Rare Pediatric Disease and Orphan Drug designations granted to LX2006, will allow for enhanced regulatory interactions and the potential for this life-improving therapy to reach FA patients more quickly.”

FDA Grants Fast Track Designation for Gene Therapy Candidate LX2006 in Friedreich Ataxia Cardiomyopathy

FDA Approves Medtronic’s Inceptiv Closed-Loop Spinal Cord Stimulator

About a week later, on April 26, the FDA approved Medtronic’s closed-loop rechargeable spinal cord stimulator (SCS), Inceptiv, as a new treatment for chronic pain. With the decision, the SCS device becomes the first on market to offer a closed-loop feature that senses biological signals along the spinal cord and automatically adjusts stimulation in real time, keeping therapy in sync with daily activities of living.7

While traditional fixed-output SCS devices deliver constant, mild electrical impulses that disrupt pain signals before they reach the brain, Inceptiv SCS constantly maintains the physicians prescribed stimulation that is tailored to the patient’s needs. The therapy includes a specialized circuitry and a proprietary algorithm to detect evoked compound action potentials (ECAPs), which are a direct measure of how much nerve tissue is activated in the spinal cord. It then senses the body’s response to stimulation 50 times per second and instantly increases or decreases stimulation to maintain prescribed settings.

"Pain is intensely personal, and stimulation therapy should meet the needs of every patient, moment to moment," Krishnan Chakravarthy, MD, PhD, director of Innovative Pain Treatment Solutions and Surgery Center, VA San Diego Healthcare, and chairman of the Empower You Chronic Pain Foundation, said in a statement.7 "Inceptiv listens to what the body is saying and, more quickly than you can blink, it seamlessly adjusts. This represents an important leap forward for the treatment of chronic pain."

FDA Approves Medtronic’s Inceptiv Closed-Loop Spinal Cord Stimulator

FDA Approves Sprinkle Formulation of Neurocrine Biosciences’ Valbenazine for Tardive Dyskinesia or Huntington disease Chorea

At the end of the month, on April 30, The FDA has approved Neurocrine Biosciences’ therapy valbenazine (Ingrezza) oral granules, a new sprinkle formulation of the treatment capsules for oral administration, for patients with tardive dyskinesia (TD) or chorea associated with Huntington disease (HD). The oral granules capsules (40 mg, 60 mg and 80 mg) are intended to be opened for sprinkling on soft foods prior to administration.8

The NDA filing for the sprinkle formulation included chemistry, manufacturing, and controls information and data demonstrating the bioequivalence and tolerability of the oral granule sprinkle capsules compared with the currently approved valbenazine capsules.9 Valbenazine is currently available as the only single-capsule, once-daily treatment option with no complex titration for adults with TD and the treatment of chorea associated with HD. It is the only selective vesicular monoamine transporter 2 (VMAT2) inhibitor that offers three effective dosages (40 mg, 60 mg and 80 mg) that can be adjusted by the healthcare provider based on patient response and tolerability.

"We developed Ingrezza Sprinkle to make administration easier for patients who have difficulty swallowing or prefer not to take a capsule," Eiry W. Roberts, MD, the chief medical officer at Neurocrine Biosciences, said in a statement.8 "We are pleased to offer the proven efficacy of Ingrezza in reducing uncontrollable movements in a new formulation."

FDA Approves Sprinkle Formulation of Neurocrine Biosciences’ Valbenazine for Tardive Dyskinesia or Huntington disease Chorea
REFERENCES
1. Abbott Receives FDA Clearance for Whole Blood Rapid Test to Help with Assessment of Concussion at the Patient's Bedside. News Release. Abbott. Published April 1, 2024. Accessed May 7, 2024. https://abbott.mediaroom.com/2024-04-01-Abbott-Receives-FDA-Clearance-for-Whole-Blood-Rapid-Test-to-Help-with-Assessment-of-Concussion-at-the-Patients-Bedside
2. Supernus Provides Regulatory Update for SPN-830. News Release. Supernus Pharmaceuticals. Published April 8, 2024. Accessed May 7, 2024. https://ir.supernus.com/news-releases/news-release-details/supernus-provides-regulatory-update-spn-830-0
3. BrainStorm Cell Therapeutics announces agreement with FDA on a special protocol assessment (SPA) for phase 3b trial in ALS. News release. BrainStorm Cell Therapeutics. April 9, 2024. Accessed May 7, 2024. https://ir.brainstorm-cell.com/2024-04-09-BrainStorm-Cell-Therapeutics-Announces-Agreement-with-FDA-on-a-Special-Protocol-Assessment-SPA-for-Phase-3b-Trial-in-ALS
4. XCOPRI® (cenobamate tablets) CV Receives FDA Approval for Alternate Methods of Administration That Include Crushed Tablet in Liquid Suspension Taken Orally or Through a Nasogastric Tube. News Release. SK Life Science. Published April 11, 2024. Accessed May 7, 2024. https://www.prnewswire.com/news-releases/xcopri-cenobamate-tablets-cv-receives-fda-approval-for-alternate-methods-of-administration-that-include-crushed-tablet-in-liquid-suspension-taken-orally-or-through-a-nasogastric-tube-302113538.html
5. Laramy J, Ferrari L. Relative Bioavailability of Cenobamate 200 Mg Administered as a Crushed Tablet Either Orally or via a Nasogastric Tube versus an Intact 200 Mg Cenobamate Tablet. Presented at: AES 2023; December 1-5; Orlando, FL. Abstract 2.257 https://aesnet.org/abstractslisting/relative-bioavailability-of-cenobamate-200-mg-administered-as-a-crushed-tablet-either-orally-or-via-a-nasogastric-tube-versus-an-intact-200-mg-cenobamate-tablet
6. Lexeo Therapeutics Granted FDA Fast Track Designation for LX2006, an AAV-Based Gene Therapy Candidate for the Treatment of Friedreich Ataxia Cardiomyopathy. News Release. Lexeo Therapeutics. Published April 16, 2024. Accessed May 7, 2024. https://ir.lexeotx.com/news-releases/news-release-details/lexeo-therapeutics-granted-fda-fast-track-designation-lx2006-aav
7. Medtronic receives FDA approval for Inceptiv closed-loop spinal cord stimulator. News release. April 26, 2024. Accessed May 7, 2024. https://news.medtronic.com/2024-04-26-Medtronic-receives-FDA-approval-for-Inceptiv-TM-closed-loop-spinal-cord-stimulator
8. Neurocrine Biosciences Announces U.S. FDA Approval of INGREZZA® SPRINKLE (valbenazine) Capsules. News release. Neurocrine. April 30, 2024. Accessed May 7, 2024. https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-us-fda-approval-of-ingrezza-sprinkle-valbenazine-capsules-302132283.html
9. Neurocrine Biosciences Announces U.S. FDA Accepts New Drug Application for INGREZZA® (valbenazine) Oral Granules Sprinkle Formulation. News Release. Published September 14, 0223. Accessed May 7, 2024. https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-us-fda-accepts-new-drug-application-for-ingrezza-valbenazine-oral-granules-sprinkle-formulation-301926943.html

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