Special Report: 2022 Neurology Drug & Device Approvals

Donepezil (Adlarity; Corium, Boston, MA)

Approved: March 14, 2022

Indication: The treatment of mild, moderate, or severe dementia from Alzheimer disease (AD)

Available as: Transdermal system: 5 mg/day or 10 mg/day

Overview: The Food and Drug Administration (FDA) approved a transdermal formulation of donepezil, an acetylcholinesterase inhibitor. This formulation is expected to increase adherence to treatment by reducing the need to remember to take medication, which can be particularly challenging for people with a condition that affects memory. The formulation also reduces the gastrointestinal side effects associated with oral formulations of donepezil. The most common side effects of Adlarity were headache, application-site pruritus, muscle spasms, insomnia, abdominal pain, application-site dermatitis, constipation, diarrhea, application-site pain, dizziness, abnormal dreams, and skin laceration.

Alzheimer Disease Pathology Assessment Test [Elecsys Phospho-Tau (181P) CSF, Elecsys β-Amyloid (1-42) CSF II; Roche Diagnostics, Basel, Switzerland]

Cleared: December 7, 2022

Indication: In vitro electrochemiluminescence immunoassays for the measurement of Phospho-Tau (181P) (pTau181) and Β-Amyloid (1-42) (Abeta42) protein concentrations in cerebrospinal fluid (CSF) from adult patients aged 55 years and older being evaluated for Alzheimer disease (AD) and other causes of cognitive impairment to generate a pTau181/Abeta42 ratio value

Available as: Immunoassays

Overview: Roche announced that the Food and Drug Administration (FDA) approved 2 new laboratory tests to measure 2 biomarkers: phosphorylated-tau (pTau181) and beta-amyloid (Abeta42) concentrations in cerebrospinal fluid (CSF). The tests, available commercially as Elecsys Phospho-Tau (181P) CSF and Elecsys Β-Amyloid (1-42) CSF II, have been previously registered in 45 countries. Results from these tests can be used to calculate a pTau181/Abeta42 ratio value that may be helpful in the evaluation of individuals aged 55 and older at risk for dementia, including Alzheimer disease (AD). The Elecsys assays will be available on cobas modular analyzer systems. Data provided by Roche in their announcement indicate that the results from the Elecsys CSF assays were 90% concordant with results obtained through amyloid PET scan imaging tests.

Trigeminal Nerve Stimulation (TNS) Device (Monarch eTNS System; NeuroSigma, Los Angeles, CA)

FDA breakthrough device designation granted: February 22, 2022

Indication: Adjunctive use for reducing the frequency of seizures in individuals 18 years of age or older diagnosed with epilepsy characterized by partial-onset seizures, with or without secondary generalization, that are refractory to 2 or more antiepileptic medications

Available as: Trigeminal Nerve Stimulation (TNS) device

Overview: This device is for adjunctive use for reducing the frequency of seizures in individuals age 18 years of age or older who are diagnosed with epilepsy characterized by partial-onset seizures, with or without secondary generalization, who are refractory to 2 or more antiepileptic medications. In a study, 40 individuals with drug-resistant epilepsy (DRE) were randomized to receive either eTNS or their usual medical treatment. Participants were followed for 1 year and evaluated for changes in seizure frequency, side effects, and quality of life. At the 6-month and 12-month timepoints, there was a 50% responder rate in individuals receiving eTNS versus a 0% responder rate among individuals randomized to the control group (P<.001). After 12 months, there was a median reduction in seizure frequency of 43.5% in the eTNS group versus 0% in the control group (P=.0013). There were no significant adverse events associated with use of the Monarch eTNS System.

Ganaxolone (Ztalmy; Marinus, Radnor, PA)

Approved: March 18, 2022

Indication: The treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD)

Available as: Oral suspension: 50 mg/mL

Overview: The Food and Drug Administration (FDA) approved ganaxolone, a neuroactive steroid that acts as a positive allosteric modulator of the GABA_A receptor, for people 2 years of age or more with seizures associated with CDD. Children and young adults treated with ganaxolone in the phase 3 Marigold trial (NCT03572933) had a median reduction of 30.7% in seizure frequency compared with a 6.9% reduction with placebo (P=.004). Seizure frequency was measured as the occurrence of major motor seizures within a 28-day period. Subjects in the Marigold open-label extension study treated with ganaxolone for at least 12 months (n=48) experienced a median 49.6% reduction in major motor seizure frequency. The most common adverse reactions reported were somnolence, fever, salivary hypersecretion, and seasonal allergy.

Fenfluramine (Fintepla; Zogenix/UCB, Emeryville, CA)

Approved for expanded indication: March 28, 2022

Indication: The treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in patients 2 years of age and older. Black Box Warning: There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in Fintepla), and valvular heart disease and pulmonary arterial hypertension.

Available as: Oral solution 2.2 mg/mL fenfluramine

Overview: Approval was based on data from a phase 3 clinical trial in which participants (n=263, 2 years of age to 35 years of age) who were treated with fenfluramine 0.7 mg/kg/day vs placebo had a 23.7% vs 8.7% reduction in seizure frequency from baseline (P=.0037). A 50% or more reduction in drop seizure frequency/28-day period occurred in almost 25% of participants treated with fenfluramine. Reductions of 50% to 75% and 75% or more were achieved by 18% and 6%, respectively, of those treated with fenfluramine. The most common adverse reactions in participants treated with fenfluramine were vomiting, diarrhea, decreased appetite, somnolence, and fatigue.

Zonisamide (Zonisade; Azurity, Woburn, MA)

Approved: July 18, 2022

Indication: Adjunctive therapy for the treatment of partial seizures in adults and pediatric patients aged 16 years and older with epilepsy

Available as: Oral suspension: 100 mg/5 mL

Overview: Zonisade became available as a liquid suspension in retail pharmacies on October 17, 2022. The oral liquid formulation of zonisamide is FDA-approved and is the only alternative formulation to solid oral doses of zonisamide. Approval was granted based on 3 double-blind, placebo-controlled, multicenter clinical trials. Most common adverse reactions reported were drowsiness, loss of appetite, dizziness, problems with coordination and balance, agitation, irritability, and difficulty memory and/or concentration.

Stiripentol (Diacomit; Biocodex, San Mateo, CA)

Approved: July 24, 2022

Indication: The treatment of seizures associated with Dravet syndrome in patients 6 months or older, weighing 15 lbs or more and taking clobazam

Available as: Capsule: 250 mg or 500 mg; Oral suspension: 250 mg or 500 mg

Overview: In 2 clinical studies, Diacomit reduced generalized clonic or tonic-clonic seizures by a median of 84% compared with 5.8% for placebo after 2 months. There are no clinical data to support the use of Diacomit as monotherapy for Dravet syndrome. Stiripentol first received FDA approval in 2018 for children 2 years of age and older. The most common adverse reactions reported were somnolence, decreased appetite, agitation, ataxia, decreased weight, hypotonia, nausea, tremor, dysarthria, and insomnia.

Vutrisiran (Amvuttra; Alnylam, Cambridge, MA)

Approved: June 13, 2022

Indication: The treatment of adults with polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults

Available as: Injection: 25 mg/0.5 mL in a single-dose prefilled syringe

Overview: In the HELIOS-A (NCT03759379) phase 3 study, participants treated with Amvuttra had a mean 2.2-point improvement on the modified Neuropathy Impairment Score +7 (mNIS+7). The placebo control group looked at participants in the APOLLO (NCT01960348) phase 3 study of patisiran which had a 14.8-point mean worsening, for a 17-point mean difference (P<.0001). After 9 months of treatment, 50% of those treated with vutrisiran reported improvements in neuropathy scores. Participants treated with vutrisiran vs placebo also had significant improvements on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) score and timed 10-meter walk test (10-MWT). In the 9 months of the study, there were no treatment-related discontinuations or deaths. The most common adverse events with Amvuttra were arthralgia, dyspnea, and decreased vitamin A.

Percutaneous Electrical Neurostimulation (PENS) Device (First Relief; DyAnsys, Palo Alto, CA)

Cleared: July 14, 2022

Indication: The treatment for the relief of chronic, intractable pain from diabetic peripheral neuropathy

Available as: Wearable percutaneous electrical neurostimulation (PENS) device

Overview: The First Relief device is placed behind the ear and releases continuous pulses of a low-level electrical current over several days. Clearance was based upon a study of sixty-three participants who were enrolled in a randomized, double-blind, single-center, controlled, prospective study who had the device applied biweekly for 16 weeks. Primary endpoint of long-term improvements in neuropathic pain in individuals with chronic pain were achieved when compared with placebo of a previously FDA cleared device in a clinical study. Results were measured in pain intensity through the Visual Analog Scale (VAS). Secondary endpoint including vibration perception threshold (VPT) value, insomnia severity index (ISI), overall neuropathy limitations scale (ONLS), and Hamilton Anxiety Rating Scale also were achieved. There were no adverse events observed during the study period.

Spinal Cord Stimulation (SCS) Implant (Eterna; Abbott, Abbott Park, IL)

Cleared: December 19, 2022

Indication: The treatment of chronic pain

Available as: Spinal cord stimulation (SCS) implant

Overview: According to materials presented by Abbott, the Eterna device is more effective than other neurostimulation devices at reducing reported pain in those being treated for chronic pain, needs to be recharged less frequently than previous devices, features an upgradable technology platform, and integrates with mobile technologies. Chronic pain affects an estimated 50 million US adults, and neurostimulation devices have been recommended by physicians for years to help their patients manage their chronic pain symptoms. Implantable neurostimulation devices deliver a mild electric signal to the epidural space, disrupting pain signals traveling between the spinal cord and the brain.

Radiologic Computer-Assisted Triage and Notification Software (Viz ANEURYSM; Viz.ai, San Francisco, CA)

Cleared: February 24, 2022

Indication: Analysis of CT angiography images of the head limited to detecting aneurysms of at least 4 mm in diameter

Available as: Artificial Intelligence (AI) software

Overview: This imaging solution software uses an AI algorithm to analyze brain imaging and identify cerebral aneurysms to ensure patients are identified and promote standardized aneurysm workflow across an entire health system. According to performance data included with the submission, the sensitivity and specificity of the viz ANEURYSM technology were 93% and 89%, respectively, compared with interpretations made by neuro-radiologists.

Tremor Transducer (StrivePD; Rune Labs, San Francisco, CA)

Cleared: June 10, 2022

Indication: Quantify kinematics of movement disorder symptoms including tremor and dyskinesia in adults aged 45 years or older with mild to moderate Parkinson’s Disease (PD)

Available as: Monitoring application software

Overview: The Food and Drug Administration (FDA) gave 510(k) clearance to this monitoring application software for Parkinson disease (PD) symptom tracking for use on the Apple Watch. The application’s combination of movement tracking and self-reported symptoms information with clinical data including brain imaging, electrophysiology, and genetics potentially enables better management for medical care. In combination with the patient’s wrist movements, the application provides a report to the clinician regarding the presence or absence of movement disorder symptoms.

Radiologic Computer-Assisted Triage and Notification software (Viz SDH; Viz.ai, San Francisco, CA)

Cleared: July 25, 2022

Indication: Analysis of non-contrast CT images of the head limited to detecting subdural hemorrhage (SDH)

Available as: Artificial Intelligence (AI) software

Overview: This artificial intelligence (AI)-powered software package automatically detects subdural hemorrage (SDH) on neuroimaging studies so the health care team can effectively triage the individual patient and provide the best indicated care. Clearance was based on a multi-center study of 500 people in which the software identified chronic or acute SDH with 94% sensitivity and 92% specificity.

Automated Radiologic Image Processing Software (Maestro Brain Model; ClearPoint Neuro, Solana Beach, CA)

Cleared: August 9, 2022

Indication: Automatic labeling, visualization, volumetric and shape qualification of segmental brain structures from a set of MRI images for identification of suspected traumatic brain injury (TBI)

Available as: Image processing software

Overview: The Food and Drug Administration (FDA) granted clearance to the Maestero Brain Model software for use by clinicians in evaluating individuals with a suspected traumatic brain injury (TBI). The software quantifies and labels the shape and volume of brain structures from MRI and detects subtle volumetric and shape abnormalities in individuals with mild TBI. Normative values were developed from a sample of 560 healthy subjects, and cross-validation showed highly reproducible results from more than 1000 MRI studies.

Alzheimer Disease Pathology Assessment Test [Elecsys Phospho-Tau (181P) CSF, Elecsys β-Amyloid (1-42) CSF II; Roche Diagnostics, Basel, Switzerland)

Cleared: December 7, 2022

Indication: In vitro electrochemiluminescence immunoassays for the measurement of Phospho-Tau (181P) (pTau181) and Β-Amyloid (1-42) (Abeta42) protein concentrations in cerebrospinal fluid (CSF) from adult patients aged 55 years and older being evaluated for Alzheimer disease (AD) and other causes of cognitive impairment to generate a pTau181/Abeta42 ratio value

Available as: Immunoassays

Overview: Roche announced that the Food and Drug Administration (FDA) approved 2 new laboratory tests to measure 2 biomarkers: phosphorylated-tau (pTau181) and beta-amyloid (Abeta42) concentrations in cerebrospinal fluid (CSF). The tests, available commercially as Elecsys Phospho-Tau (181P) CSF and Elecsys Β-Amyloid (1-42) CSF II, have been previously registered in 45 countries. Results from these tests can be used to calculate a pTau181/Abeta42 ratio value that may be helpful in the evaluation of individuals aged 55 and older at risk for dementia, including Alzheimer disease (AD). The Elecsys assays will be available on cobas modular analyzer systems. Data provided by Roche in their announcement indicate that the results from the Elecsys CSF assays were 90% concordant with results obtained through amyloid PET scan imaging tests.

Tremor Transducer (StrivePD; Rune Labs, San Francisco, CA)

Cleared: June 10, 2022

Indication: Quantify kinematics of movement disorder symptoms including tremor and dyskinesia in adults aged 45 years or older with mild to moderate Parkinson disease (PD)

Available as: Monitoring application software

Overview: The Food and Drug Administration (FDA) gave 510(k) clearance to this monitoring application software for Parkinson disease (PD) symptom tracking for use on the Apple Watch. The application’s combination of movement tracking and self-reported symptoms information with clinical data including brain imaging, electrophysiology, and genetics potentially enables better management for medical care. In combination with the patient’s wrist movements, the application provides a report to the clinician regarding the presence or absence of movement disorder symptoms.

Ublituximab (Briumvi; TG Therapeutics, New York, NY)

Approved: December 28, 2022

Indication: The treatment of relapsing forms of multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults

Available as: Injection: 150 mg/6 mL (25 mg/mL) in a single-dose vial

Overview: The approval is based on data from the phase 3 ULTIMATE I and II trials (NCT03277261 and NCT03277248), which showed that ublitumixab was more effective when compared with teriflunomide in reducing the annualized relapse rate (ARR)---the primary endpoint of the studies. In addition, data indicated that participants treated with ublitumixab experienced significantly fewer T1 Gd-enhancing lesions and new or enlarging T2 lesions compared with those treated with teriflunomide. These results represent the first phase 3 research of an anti-CD20 monoclonal antibody for relapsing MS to produce an ARR of less than 0.10, which translates into less than 1 relapse in 10 years. Adverse reactions to ublituximab include infusion reactions, upper and lower respiratory tract infections, pain in extremities, insomnia, and fatigue.

Sodium Phenylbutyrate/Taurursodiol (Relyvrio; Amylyx, Cambridge, MA)

Approved: September 29, 2022

Indication: The treatment of amyotrophic lateral sclerosis (ALS) in adults

Available as: For oral suspension: 3 g sodium phenylbutyrate and 1 g taurursodiol in single- dose packet

Overview: Approval was based on clinical trial data, including the phase 2 CENTAUR trial (NCT03127514) and its open-label extension. Across both the double-blind and open-label periods, those who had PB/TURSO vs placebo 24 weeks earlier had longer times until tracheotomy, permanent airway ventilation (PAV), or first hospitalization after diagnosis. In May 2022, the longest follow-up was 35 months, and median key event-free survival duration was 4.8 months longer in participants originally randomized to PB/TURSO vs placebo, and median tracheostomy/PAV-free survival duration was 7.3 months longer. The most common adverse events reported were abdominal pain, diarrhea, nausea, and upper respiratory tract infection.

Risdiplam (Evrysdi; Genentech, South San Francisco, CA)

Approved: May 30, 2022

Indication: Expanded indication including neonates (age 0-8 weeks) with presymptomatic, genetically confirmed spinal muscular atrophy (SMA)

Available as: For oral solution: 60 mg of risdiplam as a powder for constitution to provide 0.75 mg/mL solution. Evrysdi powder must be constituted to the oral solution by a pharmacist or other healthcare provider prior to dispensing to the patient.

Overview: The expanded indication is supported by interim safety and efficacy data from the RAINBOWFISH study (NCT03779334) showing presymptomatic neonates with SMA who were treated with risdiplam achieved key milestones such as sitting and standing with half walking at 12 months of treatment. All participants who had 2 or 3 copies of the motor neuron 2 (SMN2) gene (n=6) survived and were able to sit after 1 year of treatment. Standing was achieved by 67% of participants and independent walking was achieved by 50% of participants after 12 months of treatment. All participant were alive at 12 months without permanent ventilation. The most common adverse events found during treatment were constipation, cough, lower respiratory tract infection, upper respiratory tract infection, and vomiting.

Ravulizumab (Ultomiris; Alexion, Wilmington, DE)

Approved: April 28, 2022

Indication: The treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR+) antibody-positive

Available as: Injection: 400 mg in 20 mL (20 mg/mL) single-dose vial

Overview: In the phase 3 CHAMPION-MG trial (NCT03920293), participants treated with ravulizumab showed improvement in activities of daily living. Ravulizumab has potential to reduce treatment burden with dosing every 8 weeks. In the trial, ravulizumab was superior to placebo when comparing the change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at 26 weeks. The most common adverse events were upper respiratory tract infection and diarrhea.

Radiologic Computer-Assisted Triage and Notification Software (Viz ANEURYSM; Viz.ai, San Francisco, CA)

Cleared: February 24, 2022

Indication: Analysis of CT angiography images of the head limited to detecting aneurysms of at least 4 mm in diameter

Available as: Artificial Intelligence (AI) software

Overview: This imaging solution software that uses an AI algorithm to analyze brain imaging and identify cerebral aneurysms, to ensure patients are identified and promote standardized aneurysm workflow across an entire health system. According to performance data included with the submission, the sensitivity and specificity of the viz ANEURYSM technology were 93% and 89%, respectively, compared with interpretations made by neuro-radiologists.

Automated Radiologic Image Processing Software (Maestro Brain Model; ClearPoint Neuro, Solana Beach, CA)

Cleared: August 9, 2022

Indication: Automatic labeling, visualization, volumetric and shape qualification of segmental brain structures from a set of MRI images for identification of suspected traumatic brain injury (TBI)

Available as: Image processing software

Overview: The Food and Drug Administration (FDA) granted clearance to the Maestero Brain Model software for use by clinicians in evaluating individuals with a suspected traumatic brain injury (TBI). The software quantifies and labels the shape and volume of brain structures from MRI and detects subtle volumetric and shape abnormalities in individuals with mild TBI. Normative values were developed from a sample of 560 healthy subjects, and cross-validation showed highly reproducible results from more than 1000 MRI studies.