2020 Neurology Drug & Device Approvals

Suvorexant (Belsomra; Merck, Kenilworth, NJ)

Approved: January 29, 2020

Indication: insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Available as: Tablets (5 mg, 10 mg, 15 mg, and 20 mg)

Based on a randomized, double-blind, placebo-controlled, clinical trial (NCT02750306), suvorexant (Belsomra; Merck, Kenilworth, NJ) was approved specifically for use in adults with mild-to-moderate Alzheimer disease (AD). Individuals with AD are more likely to have insomnia than those in the general population at the same age. In the clinical trial, adults age 50 to 90 with mild-to-moderate AD and insomnia were treated with suvorexant (n=142) or placebo (n=143).

The initial dose of suvorexant was 10 mg, which was increased to 20 mg in 77% of participants after 2 weeks. The recommended dosing is the lowest effective dose tolerated. As assessed objectively with polysomnography, individuals treated with suvorexant had statistically significant improvements in total sleep time (TST) and wake after sleep onset (WASO) compared with those who received placebo.

¹⁸F-Fluortaucipir (Lilly; Indianapolis, IN)

Approved: May 28, 2020

Indication: evaluation of tau neurofibrillary tangle (NFT) density and distribution with positron-emission tomography

Available as: multidose vial (300-1900 MBq/mL [8.1-51 mCi/mL])

The Food and Drug administration (FDA) approved the radiotracer ¹⁸F-flortaucipir (Tauvid; Eli Lilly, Indianapolis, IN) for use with positron emission tomography (PET) of the brain. ¹⁸F-flortaucipir-PET is used to evaluate density and distribution of tau neurofibrillary tangles (NFTs) in people with cognitive disorders that may be a tauopathy, such as Alzheimer disease (AD). In clinical studies, flortaucipir had sensitivity ranging from 92% (95% CI, 80-97) to 100% (95% CI, 91-100) and specificity from 52% (95% CI, 34-70) to 92% (95% CI, 75-98) in the primary efficacy cohort. A neuropathologic diagnosis of AD requires demonstration of both amyloid β neuritic plaques and tau NFTs in the brain. Flortaucipir is the first and only approved diagnostic agent to image tau NFTs in the brain. Interreader agreement was 0.87 (95% CI: 0.83, 0.91) across 241 participants, using the Fleiss’ kappa statistic.

Diazepam Nasal Spray (Valtoco; Neurelis, San Diego, CA)

Approved: January 10, 2020

Indication: acute treatment of acute repetitive (cluster) seizures different from individual’s seizure pattern in those age 6 years or more

Available as: 0.1 mLnasal spray delivering 5 mg, 7.5 mg, or 10 mg diazepam

This diazepam nasal spray (Valtoco; Neurelis, San Diego, CA) is a new formulation of diazepam, and was generally safe and well-tolerated during a long-term clinical safety study (NCT02724423). The most common adverse reactions (at least 4%) were somnolence, headache, and nasal discomfort. The proprietary formulation and delivery mechanism incorporates a transmucosal absorption enhancement technology (Intravail; Neurelis) that enables noninvasive delivery of a broad range of protein, peptide, and small molecule drugs.

Vigabatrin (Sabril; Lundbeck, Deerfield, IL)

Approved: January 27, 2020

Indication: adjunctive treatment of refractory complex partial seizures in people over age 2 years

Available as: tablet or powder for reconsitution (500 mg)

Already approved for refractory partial seizures in people age 10 or more or infantile spasms for infants age 1 month to 2 years, vigabatrin (Sabril, Lundbeck, Deerfield, IL) indications were expanded to include individuals age 2 to 10 years.

Approval was supported by a study funded by the Tuberous Sclerosis Alliance (TS Alliance) that included review of 198 medicals at 13 clinics treating children with tuberous sclerosis complex (TSC) in the US.

Vigabatrin carries a warning that use increases the risk of permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. Permanent blindness may occur with prolonged use.

Fenfluramine (Fintepla; Zogenix, Emeryville, CA)

Approved: June 25, 2020

Indication: seizures associated with Dravet syndrome (DS) in individuals age 2 years or more

Available as: oral solution: 2.2 mg/mL

Fenfluramine (Fintepla; Zogenix, Emeryville, CA) approval was based on data from 2 randomized, double-blinded, placebo-controlled phase 3 clinical trials, published in The Lancet and JAMA Neurology, and safety data from an open-label extension trial in which participants were treated for up to 3 years. As adjunctive treatment, fenfluramine significantly reduced the monthly convulsive seizure frequency compared with placebo in participants whose seizures were not adequately controlled on 1 or more antiseizure medications. Most study participants treated with fenfluramine experienced benefits within 3 to 4 weeks, which remained consistent.

In study 1504 phase 3 study (NCT02926898), participants with DS treated with stiripentol who still had a high number of convulsive seizures had a significant and clinically meaningful (>50%) reduction in monthly convulsive seizure frequency (MCSF). The median longest seizure-free interval was 22 days (3.0-105.0) with fenfluramine and 13 days (1.0-40.0) with placebo (P=.004).

The most common adverse reactions were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; blood pressure increased; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; and status epilepticus.

Cannabidiol (Epidiolex; GW Pharma, Carlsbad, CA)

Approved: October 22, 2020

Indication: seizures associated with tuberous sclerosis complex (TSC)

Available as: oral solution (100 mg/mL)

Already approved for the treatment of seizures related to Lennox-Gastaut and Dravet syndromes, prescription pharmaceutical cannabidiol (ppCBD) (Epidiolex; GW Pharma, Carlsbad, CA) is an oral solution now approved to treat seizures associated with TSC in people age 1 year or more. The age range for treatment of seizures associated with DS or LGS were expanded to include individuals age 1 and up.

The recommended maintenance dose for tuberous sclerosis is 25 mg/kg/day, which is supported by data from a phase 3 safety and efficacy study during which treatment with ppCBD reduced seizure frequency by 48% compared with 24% for placebo (P<0.01).

In 2020, ppCBD was also descheduled by the Drug Enforcment Agency (DEA), such that it is no longer a controlled substance. The most common adverse events with ppCBD were diarrhea, transaminase elevations, decreased appetite, somnolence, pyrexia, and vomiting. The safety profile observed in this study was generally comparable to that observed in prior studies of ppCBD.

Lacosamide (Vimpat; UCB, Atlanta, GA)

Approved: November 16, 2020

Indication: adjunctive treatment of primary generalized tonic-clonic seizures in people age 4 or more

Available as: tablets (50 mg, 100 mg, 150 mg, 200 mg), single-dose vial (200 mg/20 mL) for intravenous use, oral solution (10 mg/mL)

Lacosamide (Vimpat; UCB, Atlanta, GA), already approved for treatment of partial onset seizures in people with epilepsy age 4 years or more, was approved as adjunctive therapy for primary generalized tonic-clonic seizures (PGTCS) in people age 4 years or more. Additionally, lacosamide injection for intravenous use was approved for children age 4 years and up.

Approval was based on a study published in the Journal of Neurology, Neurosurgery & Psychiatry that showed adjunctive lacosamide lowered the risk of developing a second PGTCS during a 24-week treatment period, with risk reduction of 45% (P=.001) and a significantly higher rate of freedom from PGTCS during the treatment period compared with placebo (31.3% vs 17.2%, P=.011).

The most common adverse reactions (≥10%) with lacosamide were dizziness (23%), somnolence (17%), headache (14%), and nausea (10%) compared to 7%, 14%, 10%, and 6%, respectively, of participants who received placebo.

Eptinezumab (Vyepti; Lundbeck, Deerfield, IL)

Approved: February 21, 2020

Indication: preventive treatment of chronic migraine

Available as: single-dose vial (100 mg/mL)

Eptinezumab (Vyepti; Lundbeck, Deerfield, IL) is the first intravenously administered monoclonal antibody inhibitor of calcitonin gene-related peptide (CGRP) and the fourth drug in this class (CGRP inhibitors) to be approved. Eptinezumab is administered intravenously every 3 months.

In clinical trials, 56.3% of those with episodic migraine treated with eptinezumab achieved at least a 50% reduction in migraine days per month (MMD) vs 37.4% of those treated with placebo (nominal P=.009). For those with chronic migraine treated with 300 mg of eptinezumab, 61.4% (P<.001) vs 39.3% of those who received placebo had at least a 50% reduction in MMD. Treatment benefit was observed as early as day 1 after infusion and sustained over 6 months with quarterly dosing. Some individuals may benefit from a higher dose of 300 mg every 3 months. Few adverse events occurred; nasopharyngitis and infusion site reactions were most common.

Rimegepant (Nurtec; Biohaven, New Haven, CT)

Approved: February 27, 2020

Indication: acute treatment of migraine

Available as: orally disintegrating tablet (100 mg/mL)

Rimegepant (Nurtec; Biohaven, New Haven, CT) is administered as a fast-acting orally disintegrating table and a single dose of 75 mg provides pain relief within 1 hour. Rimegepant also has sustained efficacy with pain relief lasting for as long as 48 hours for many. In clinical trials, 86% of participants treated with a single dose of rimegepant did not need another rescue medication with 24 hours.

Rimegepant has no cardiac contraindications and few side effects. Over 3,100 individuals took more than 113,000 doses in clinical trials, including a 1-year long-term safety study. The most common adverse reaction was nausea (2%) in those who received rimegepant vs 0.4% of those who received placebo.

Implantable Neuromuscular Stimulator (Reactiv8; Mainstay Medical, Brooklyn Center, MN)

Approved: June 16, 2020

Indication: bilateral stimulation of L2 medial branch of dorsal ramus at L3 transverse process for intractable chronic low back pain associated with multifidus muscle dysfunction

Available as: surgically implantable device

The Food and Drug Administration (FDA) granted premarket approval for an implantable neurostimulation system (ReActiv8; Mainstay, Brooklyn Center, MN) to aid treatment of intractable chronic low back pain (CLBP).

The device is indicated for intractable CLBP associated with multifidus muscle dysfunction, as evidenced by imaging or physiologic testing in adults whose pain has not responded to pain medications or physical therapy, and are not candidates for spine surgery. Bilateral stimulation of the L2 medial branch of the dorsal ramus nerve as it crosses the transverse process at L3 elicits contraction of the lumbar multifidus, which can lead to improvement in CLBP and its disabling effects.

The FDA approval of the neurostimulation system is based on results from the ReActiv8-B clinical study (NCT02577354), a pivotal international multicenter prospective randomized active sham-controlled blinded trial in 204 participants with 1-way crossover, conducted under an Investigational Device Exemption (IDE) from the FDA.

Remote Neurostimulator (Nerivio; Theranica, Netanya, Israel)

Cleared: October 23, 2020

Indication: preventive treatment of chronic migraine

Available as: a handheld device controlled with an application on a smartphone (iOS or Android) for self-administration

Approved for acute migraine in 2019, this handheld neurostimulator (Nerivio; Theranica, Montclair, NJ) was also approved for preventive treatment of chronic migraine in 2020. The device provides remote electric neuromodulation applied to the arm or trunk to create conditioned pain modulation (CPM).

In an open-label pilot study, results of which were published in Pain & Therapy, 38 participants with chronic migraine with or without aura received REN or sham treatment with the device. With REN, 73.7% (28/38) of participants achieved pain relief at 2 hours and 26.3% (10/38) achieved pain freedom for at least half of their REN-treated attacks. Consistent pain relief at 24 hours was experienced by 84.4% (32/38) and 45% (17/38) had sustained pain relief at 24 hours in at least 50% of their treated attacks. Incidence of device-related adverse events was less than 2%.

Each device prescription includes 12 treatments, after which it can be recycled, and the prescription refilled with a new dispensed device.

Opicapone (Ongentys; Neurocrine Biosciences, San Diego, CA)

Approved: April 24, 2020

Indication: intermittent treatment of OFF episodes in patients with Parkinson disease treated with carbidopa/levodopa

Available as: capsules (25 mg, 50 mg)

Once-daily oral opicapone (Ongentys; Neurocrine Biosciences, San Diego, CA) was approved as add-on treatment to levodopa/carbidopa for Parkinson disease (PD) off episodes.

In the BIPARK clinical studies (BIPARK-1 [NCT01568073] and BIPARK-2 [NCT01227655]), a 50 mg dose of opicapone significantly reduced off time from baseline to week 14 or 15 compared with placebo. On time without troublesome dyskinesia also increased from baseline to week 14 or 15 compared with placebo. Pooled safety data from the BIPARK-1 and BIPARK-2 studies showed the most common adverse reactions with opicapone, incidence at least 4% and greater than placebo, were dyskinesia, constipation, elevated blood creatine kinase, hypotension/syncope, and weight decrease.

Apomorphine Sublingual (Kynmobi; Sunovion, Marlborough, MA)

Approved: May 21, 2020

Indication: acute, intermittent treatment of “off” episodes of Parkinson disease (PD)

Available as: sublingual film (10 mg,15 mg, 20 mg, 25 mg, and 30 mg)

Approval of apomorphine sublingual film (Kynmobi; Sunovion, Marlborough, MA) was based on multiple clinical trials. In the pivotal phase 3 clinical trial (NCT02469090), published in Lancet Neurology, treatment with apomorphine sublingual film provided statistically significant and clinically meaningful improvement in motor symptoms vs placebo.

Ozanimod (Zeposia; Celgene, Summit, NJ)

Approved: March 25, 2020

Indication: relapsing multiple sclerosis (MS) including clinically isolated syndrome (CIS) and active secondary progressive MS (aSPMS) in adults

Available as: capsules (0.23 mg, 0.46 mg, or 0.92 mg)

Ozanimod (Zeposia; Bristol Myers Squibb, New York, NY) is a daily oral medication taken (0.92 mg/day). Titration is used to reach the maintenance dosage, because transient heart rate decreases and atrioventricular conduction delays may occur.

Treatment with ozanimod compared with interferon resulted in relative reductions (years 1 and 2 respectively) for annualized relapse rate (ARR; 51% and 60%), number of gadolinium-enhancing (Gd⁺) lesions (63% and 53%) and new or enlarging lesions on T2 MRI (48% and 42%).

Adverse reactions (incidence ≥4%) were upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension. Ozanimod has cardiovascular contraindications and should not be used in those with severe untreated sleep apnea or usingmonoamine oxidase (MAO) inhibitors. Complete blood count including lymphocyte count, ECG, liver function tests, and medication history including vaccination should be obtained and reviewed before initiating ozanimod treatment. History of uveitis or macular edema mandates ophthalmic tests.

Inebulizumab (Uplizna; Viela Bio, Gaithersburg, MD)

Approved: June 12, 2020

Indication: antiaquaporin-4 positive (AQP4)⁺ neuromyelitis optica spectrum disorder (NMOSD)

Available as: single-dose vial (100 mg/10 mL) for dilution and intravenous administration

Inebilizumab (Uplizna; Viela Bio, Gaitherburg, MD) is a twice-a-year maintenance regimen after initial doses. Approval was based in part on a pivotal trial in adults with NMOSD (213 antiAQP4⁺ and 17 antiAQP4^– participants). Of those who were antiAQP4⁺, 89% remained relapse-free during the 6-month period posttreatment, compared with 58% of those taking placebo. Inebulizumab had a favorable safety and tolerability profile. The most common adverse reactions (greater than 10%) were urinary tract infection (20%), nasopharyngitis (13%), infusion reaction (12%), arthralgia (11%), and headache (10%).

Satralizumab (Enspryng; Genentech, South San Francisco, CA)

Approved: August 16, 2020

Indication: antiaquaporin-4 positive (AQP4)⁺ neuromyelitis optica spectrum disorder (NMOSD)

Available as: single-dose prefilled syringe (120 mg/mL)

Satralizumab (Enspryng; Genentech, South San Francisco, CA) is a self-administered subcutaneous injection. administered every 4 weeks after an initial loading dose.

Approval was supported by results from clinical trials of satralizumab as monotherapy or adjunctive treatment of NMOSD. With monotherapy, 76.5% of participants treated with satralizumab were relapse-free at 96 weeks compared with 41.1% of those treated with placebo. As adjunctive treatment to immunosuppressive therapy, 91.1% of participants treated with satralizumab were relapse-free at 9 weeks compared with 56.8% of those treated with placebo. In both studies, all participants were antiAQP4⁺. The most common adverse reactions with satralizumab were nasopharyngitis, headache, upper respiratory tract infection, gastritis, rash, arthralgia, extremity pain, fatigue, and nausea.

Satralizumab is the only approved NMOSD therapy that targets interleukin-6 (IL-6) receptor activity, believed to play a key role in the inflammation associated with NMOSD.

Ofatumumab (Kesimpta; Novartis, East Hanover, NJ)

Approved: August 20, 2020

Indication: relapsing forms of multiple sclerosis (MS) including clinically isolated syndrome (CIS) and active secondary progressive MS (aSPMS) in adults

Available as: s/pen (20 mg/0.4 mL)

Ofatumumab (Kesimpta; Novartis, East Hanover, NJ) is a subcutaneous autoinjection with superior efficacy compared with teriflunomide (Aubagio; Sanofi, Bridgewater, NJ) with a similar safety profile. Ofatumumab is the first B-cell therapy that can be self-administered once monthly at home via the Sensoready autoinjector pen.

In clinical trials, ofatumumab (20 mg/month, subcutaneous) vs active comparator teriflunomide (14 mg/day, oral) resulted in significantly lower annualized relapse rate (ARR) (0.11 vs 0.22) and 59% (0.10 vs 0.25)(P<.001 in both studies) and conferred a 34.4% (P<.002)relative risk reduction in 3-month confirmed disability progression. Both studies were published in the New England Journal of Medicine.

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

Approved: August 7, 2020

Indication: treatment of spinal muscular atrophy (SMA) (age 2 months and up)

Available as: powder (60 mg) for reconstitution (0.75 mg/mL)

Risdiplam (Evrysdi; Genentech, South San Francisco, CA) is an oral daily treatment administered as a liquid, taken by mouth or via a feeding tube in individuals who need parenteral nutrition.

Treatment of infants with type 1 SMA with risdiplam resulted in meaningful improvements in motor function, including developing the ability to sit without support for at least 5 seconds—a key motor milestone not typically seen in the natural course of the disease. Survival without permanent ventilation at 12 and 23 months was improved compared with natural history. In children and adults with type 2 or 3 SMA treated with risdiplam, statistically significant and clinically meaningful motor function improvements on the Motor Function Measure-32 (MFM-32) total score (1.36 points [95% CI: 0.61, 2.11]) were seen compared with those treated with placebo (-0.19 points [95% CI: -1.22, 0.84], P=.0156).

Risdiplam is an RNA-splicing modulator that increases production of survival of motor neuron protein (SMN). Risdiplam was found safe as well as effective. The most common adverse reactions were fever, diarrhea, and rash in all participants; infants also experienced upper respiratory tract infection, pneumonia, constipation, and vomiting. No treatment-related adverse events led to withdrawal from either study.

Viltolarsen (Viltepso; NS Pharma, Paramus, NJ)

Approved: August 18, 2020

Indication: Duchenne muscular dystrophy (DMD) with confirmed mutation of dystrophin amenable to exon 53 skipping

Available as: single-dose vial (250 mg/5 mL) for intra-venous administration

Viltolarsen (Viltepso; NS Pharma, Paramus, NJ) ifor intravenous injection approval was based on evidence that it increases production of dystropin by approximately tenfold. Treatment with viltolarsen infusions can be administered at home, in the hospital, or at an outpatient treatment center. Viltolarsen is administered by a trained healthcare professional as an 80 mg/kg body weight weekly. Because a lack of dystrophin is the underlying cause of DMD, increasing dystrophin as much and as early as possible is a key goal in the treatment of DMD. Viltolarsen is the first and only exon 53-skipping therapy to demonstrate an increase in dystrophin in children age 4 years or less. The continued approval of viltolarsen may be contingent on confirmation of a clinical benefit.

The most common adverse events were upper respiratory tract infection, injection site reaction, cough, and fever.

Mixed Salts Oxybate (Xywav; Jazz Pharmaceuticals, Philadelphia, PA)

Approved: July 21, 2020

Indication: cataplexy or excessive daytime sleepiness associated with narcolepsy (age ≥7 years)

Available as: functionally scored tablets (75 mg or 150 mg)

This calcium, magnesium, potassium, and sodium oxybate oral solution (Xywav; Jazz Pharmaceuticals, Philadelphia, PA) has 92% less sodium, or approximately 1,000 to 1,500 mg less per night, compared with the already available sodium oxybate at the recommended dose range of 6 to 9 g/night.

A global phase 3 double-blind placebo-controlled randomized-withdrawal multicenter study demonstrated statistically significant improvement (P<.0001) in the number of weekly cataplexy attacks and Epworth sleepiness scale scores for those treated with this oxybate compared with placebo.

Multiple dosing options are available and titration can be done as unequal doses taken over the course of the night. When starting the new oxybates compound in someone who had been using sodium oxybate, the starting dose for the new oxybates is as they were taking sodium oxybate (gram for gram), titrated as needed based on efficacy and tolerability.

Flow Diverter (Flow Redirection Endoluminal Device [FRED], Microvention, Alisa Viejo, CA)

Approved: December 16, 2019

Indication: wide-necked (≥4 mm or dome-to-neck ratio <2) saccular/fusiform intracranial aneurysms from vessel with diameter 2-5 mm

Available as: self-expanding nickel-titanium implant on a delivery system

This flow diverter (Flow Redirection Endoluminal Device [FRED] device; MicroVention, Aliso Viejo, CA) is the first with self-expanding braided nitinol mesh to be granted premarket approval in the US. The self-expanding mesh redirects blood flow to promote aneurysm occlusion. The interwoven nitinol design of the device allows for smooth delivery to the target aneurysm, as well as reliable opening and vessel wall apposition, for high treatment durability.

The device has been CE marked in Europe since 2013, indicating conformity with health standards, and safely used in nearly 20,000 procedures, including published studies. The FRED device pivotal study (NCT01801007) supporting premarket approval in the US adds new evidence to the large existing body of global clinical data, further demonstrating the safety and effectiveness of the device.

Radial Artery Catheter for Neurovascular Access (Rist Cath Radial Access Long Sheath; RIST Neurovascular, Miami Beach, FL)

Cleared: December 23, 2019

Indication: introduction of interventional devices into the peripheral, coronary, and neurovasculature

Available as: single lumen, variable stiffness stainless steel and nitinol catheter with radiopaque marker band

This device is the first neurointerventional device (RIST Cath Radial Access Long Sheath; RIST Neurovascular, Miami Beach, FL) to provide access to the neurovasculature through the radial artery in the wrist. Cardiology studies showed a significant reduction in access site complications and mortality with radial access (NCT04077762). Other advantages include individual preference, immediate ambulation, and reduced costs.

Ticagrelor (Brilinta; Astra Zeneca, Wilmington, DE)

Approved: November 6, 2020

Indication: secondary stroke prevention with aspirin in individuals who had acute ischemic stroke (AIS) or high-risk transient ischemic attack (TIA)

Available as: tablets (60 mg and 90 mg)

Previously approved for treatment of individuals with acute coronary syndrome or myocardial infarction, the expanded indication of ticagrelor (Brilinta; AstraZeneca, Wilmington, DE) for secondary stroke prevention was based, in part, on results from the THALES phase 3 trial (NCT03354429). In that trial, aspirin plus ticagrelor 90 mg reduced the composite rate of stroke and death by 17% (hazard ratio [HR], 0.83; 95% CI: .71-.96; P=.015) compared with aspirin treatment alone in those who had AIS or high-risk TIA. The primary composite endpoint was driven by a reduction in stroke.

The risk for severe bleeding events was 0.5% in participants receiving aspirin plus ticagrelor and 0.1% for aspirin alone, which are in line with the known safety profile of ticagrelor. Full data from the THALES phase 3 trial were published in The New England Journal of Medicine.