Special Report: 2023 Neurology Drug & Device Approvals

ALZHEIMER DISEASE & DEMENTIA

Rexuliti (brexpiprazole; Otsuko, Princeton, NJ; Lundbeck, Deerfield, IL)

Approval granted on: July 10, 2015

Approval for new indication granted on: May 10, 2023

Indication: Treatment of agitation associated with dementia due to Alzheimer disease.

Administration: Administer Rexulti orally, once daily with or without food.

The recommended starting Rexulti dosage for the treatment of agitation associated with dementia due to Alzheimer disease (AD) is 0.5 mg taken once daily on days 1 to 7. Increase the dosage on days 8 through 14 to 1 mg once daily, and on day 15 to 2 mg once daily. The recommended target dose is 2 mg once daily. The dosage can be increased to the maximum recommended daily dosage of 3 mg once daily after at least 14 days, based on clinical response and tolerability.

Boxed warning: Rexulti’s label contains a boxed warning for increased mortality in adult patients with dementia-related psychosis and suicidal thoughts and behaviors.

Overview: Rexulti, which is currently indicated for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder in adults and for the treatment of schizophrenia in adult and pediatric patients aged 13 years and older, received approval by the Food and Drug Administration (FDA) to treat agitation associated with dementia related to AD. This approval represents the first pharmacologic treatment approved for agitation in this population, although it’s important to note that Rexulti is not indicated as an as needed (“prn”) treatment. Estimates suggest that up to 50% of individuals diagnosed with AD experience agitation, which is characterized by aggressive behaviors, physically nonaggressive behaviors, verbally agitated behaviors, and/or hiding and hoarding. There are serious side effects associated with treatment with Rexulti, including cerebrovascular problems, neuroleptic malignant syndrome, tardive dyskinesia, and metabolic problems such as hyperglycemia, diabetes, and dyslipidemia.

Alzheimer disease pathology assessment test: Elecsys ß-Amyloid (1-42) CSF II, Elecsys Total-Tau CSF (Roche Diagnostics, Indianapolis, IN)

510(k) clearance granted on: June 5, 2023

Indication: In vitro electrochemiluminescence immunoassays for the measurement of the ß-Amyloid (1-42) (Abeta42) and Total-Tau (tTau) 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 tTau/Abeta42 ratio value.

Available as: Immunoassays

Overview: Roche (Basel, Switzerland) announced that the US Food and Drug Administration (FDA) has issued 501(k) clearance to assays that measure 2 biomarkers, beta-amyloid and tau proteins, used to evaluate AD pathology based on the cerebrospinal fluid (CSF) of adults aged 55 and older. These are the Elecsys beta-Amyloid (1-42) CSF II assay (Abeta42) and the Elecsys Total-Tau CSF assay (tTau), used as a tTau/Abeta42 ratio. The new assays add to Roche’s already available Elecsys Abeta42 and Elecsys Phospho-Tau (181-P) CSF (pTau181) assays, used as a pTau181/Abeta42 ratio, which received 501(k) clearance in 2022. The Elecsys assays will be available on cobas modular analyzer systems.

Leqembi (lecanemab-irmb; Eisai, Tokyo, Japan; Biogen, Cambridge, MA)

Accelerated approval granted on: March 6, 2023

Approval granted on: July 6, 2023

Indication: Treatment of Alzheimer disease (AD). Treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.

Administration: The recommended dosage of Leqembi is 10 mg/kg that must be diluted then administered as an intravenous infusion over approximately one hour, once every two weeks.

If an infusion is missed, administer the next dose as soon as possible.

Boxed Warning: Leqembi’s label contains a boxed warning for amyloid related imaging abnormalities (ARIA), including both ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). The risk of ARIA is greater in people who test positive for apolipoprotein E Ε4 (ApoE Ε4) homozygotes.

Overview: The Food and Drug Administration (FDA) granted traditional approval to Leqembi for the treatment of people with AD. This follows the FDA’s January 2023 decision to approve Leqembi via the accelerated approval pathway, and the March 2023 decision to grant Leqembi priority review for approval with the prescription drug user fee act (PDUFA) action date of July 6, 2023. Leqembi is a humanized immunoglobulin gamma 1 (lgG1) monoclonal antibody directed against aggregated soluble (“protofibril”) and insoluble forms of AΒ for the treatment of those diagnosed with AD with mild cognitive impairment or mild dementia stage of disease and confirmed presence of AΒ pathology.

AIRAscore (AIRAmed, Tübingen, Germany)

510(k) clearance granted on: August 25, 2023

Indication: Automatic labeling, visualization and volumetric quantification of segmentable brain structures from a set of MR images.

Available as: Radiological image processing system.

Overview: AIRAmed announced that the Food and Drug Administration (FDA) has granted the company 510(k) clearance to market the AIRAscore (AIRAmed, Tübingen, Germany) software in the United States. AIRAscore provides brain volumetry data based on MRI brain scans using deep learning and artificial intelligence (AI) to assist in the detection of brain volumetric changes that may be associated with various neurologic conditions, including Alzheimer disease (AD), frontotemporal dementia, and other dementias. AIRAscore has been available in Europe for 4 years and is expected to be available in the United States in the first quarter of 2024.

VUNO Med-DeepBrain (VUNO, Seoul, South Korea)

510(k) clearance granted on: October 4, 2023

Indication: Automatic labeling, quantification and visualization of segmentable brain structures from a set of MR images.

Available as: Automated radiological image process software.

Overview: VUNO announced that the Food and Drug Administration (FDA) has granted the company 510(k) clearance to market VUNO Med-DeepBrain (VUNO, Seoul, South Korea) in the United States. VUNO Med-DeepBrain is an artificial intelligence (AI)-based software that extracts quantitative data of the brain from MRI scans. The software uses brain parcellation to provide volumetric data on multiple brain regions, while also evaluating white matter hyperintensity (WMH) and cortical thickness.

BrainSpec Core (BrainSpec, Boston, MA)

510(k) clearance granted on: November 14, 2023

Indication: A post-processing application to analyze and evaluate MR (magnetic resonance) spectroscopy data. It provides evaluation of MR Single Voxel Spectroscopy (SVS) data and MR Chemical Shift Imaging (CSI) data to support the diagnostic process.

Available as: Radiological image processing system.

Overview: The Food and Drug Administration (FDA) has awarded clearance to the artificial intelligence (AI) software platform BrainSpec Core (BrainSpec, Boston, MA) as a tool for measuring brain chemistry noninvasively based on magnetic resonance spectroscopy (MRS) data. BrainSpec Core is designed to assist clinicians in the evaluation and diagnosis of neurologic conditions including Alzheimer disease (AD), multiple sclerosis (MS), epilepsy, brain tumors, and traumatic brain injury (TBI). This is the first FDA clearance for a software that uses a brain chemistry reference database. BrainSpec Core previously received FDA breakthrough device designation as a tool for estimating isocitrate dehydrogenase (IDH) status in people with glioma.

EPILEPSY & SEIZURES

Daybue (trofinetide; Acadia Pharmaceuticals, San Diego, CA)

Approval granted on: March 10, 2023

Indication: Treatment of Rett syndrome in adults and pediatric patients 2 years of age and older.

Administration: Administer Daybue orally or via gastronomy (G) tube twice daily, in the morning and evening, according to patient weight.

Overview: The Food and Drug Administration (FDA) has approved Daybue for the treatment of Rett syndrome in adult and pediatric patients 2 years of age and older. This drug represents the first and only approved therapy for the rare genetic neurodevelopmental disorder, which is associated with a progressive loss of motor skills and language. Daybue is a synthetic version of a naturally occurring molecule, tripeptide glycine-proline-glutamate (GPE). Common adverse reactions for Daybue include diarrhea and vomiting.

OneRF Ablation System (NeuroOne, Eden Prairie, MN)

510(k) clearance granted on: December 6, 2023

Indication: Creation of radiofrequency lesions in nervous tissue for functional neurosurgical procedures.

Available as: Radiofrequency lesion generator.

Overview: The Food and Drug Administration (FDA) has granted 510(k) clearance to the OneRF Ablation System (NeuroOne, Eden Prairie, MN), according to an announcement from NeuroOne. The OneRF Ablation System produces radiofrequencies that generate heat to ablate nervous tissue for use in neurosurgery, with applications in Parkinson disease, epilepsy, dystonia, essential tremor, and other neurologic conditions. This is the first thin-film, stereoelectroencephalogram (sEEG)-guided radiofrequency ablation system to receive FDA clearance, providing a temperature-controlled environment in the neurosurgery setting. The OneRF Ablation System is expected to launch in 2024.

HEADACHE & PAIN

Zavzpret (zavegepant; Pfizer, New York, NY)

Approval granted on: March 9, 2023

Indication: Acute treatment of migraine with or without aura in adults

Administration: The recommended dose of Zavzpret is 10 mg given as a single spray in one nostril, as needed.

The maximum dose that may be given in a 24-hour period is 10 mg (1 spray). The safety of treating more than 8 migraines in a 30-day period has not been established.

Overview: The Food and Drug Administration (FDA) approved a new nasal spray for the treatment of acute migraine with or without aura in adults. Zavzpret represents the first intranasal-administered small molecule calcitonin gene-related peptide (CGRP) receptor antagonist to be approved for migraine treatment. FDA approval was based on results from 2 randomized, double-blind placebo-controlled trials, including a phase 3 study (NCT04571060) on the safety, tolerability, and efficacy of Zavzpret for the treatment of acute migraine. Results from this phase 3 study, published in the March issue of The Lancet Neurology, showed that, 2 hours post-dose, a higher percentage of individuals treated with Zavzpret 10 mg nasal spray reported more pain freedom and freedom from their most bothersome symptom than those administered a placebo.

RizaFilm (rizatriptan; Intelgenx Corp, Saint-Laurent, Canada)

Approval granted on: April 18, 2023

Indication: Acute treatment of migraine with or without aura in adults and in pediatric patients 12 to 17 years of age weighing 40 kg or more.

Administration: The recommended dose of RizaFilm in adults is 10 mg administered on the tongue. The maximum cumulative dose that may be given in 24 hours is 30 mg, with doses separated by at least 2 hours. The safety of treating, on average, more than four headaches in a 30-day period has not been established.

Overview: The Food and Drug Administration (FDA) has approved RizaFilm, an oral film formulation of rizatriptan, for the treatment of acute migraine. Rizafilm is a serotonin (5-HT) 1B/1D receptor agonist (triptan) indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 12 to 17 years of age weighing 40 kg or more. The therapy is a proprietary oral thin film formulation of the drug (10 mg rizatriptan) administered on the tongue. The most common adverse reactions reported in adults were (incidence ≥ 5% and greater than placebo): asthenia/fatigue, somnolence, pain/pressure sensation, dizziness, and nausea. IntelGenx Corp reports that it has entered into a licensing, development, and supply agreement with Gensco Pharma for the exclusive commercialization of Rizafilm in the United States.

Quilipta (atogepant; AbbVie, Chicago, IL)

Approval granted on: September 28, 2021

Approval of expanded indication granted on: April 17, 2023

Indication: Preventive treatment of migraine in adults.

Administration: Quilipta is taken orally with or without food. The recommended dosage of Quilipta for episodic migraine is 10 mg, 30 mg, or 60 mg taken once daily. The recommended dosage of Quilipta for chronic migraine is 60 mg taken once daily

Overview: The Food and Drug Administration (FDA) has approved expanding the indication of Quilipta 60 mg/d to include the preventive treatment of chronic migraine in adults. The expanded indication provides an additional treatment option for those with chronic migraine, a diagnosis for those who experience migraines at least 8 times per month for at least 3 months.

In 2021, the FDA approved Quilipta, a calcitonin gene-related peptide receptor antagonist, for the treatment of episodic migraine. Quilipta is contraindicated in those with kidney or liver problems or in those who are pregnant or planning to become pregnant. The overall safety profile of Quilipta is similar to side effects seen with treatment of episodic migraine with Quilipta and includes constipation, nausea, and fatigue/sleepiness as the most common adverse events.

IMAGING & TESTING

ANDI (Imeka, Sherbrooke, Canada)

510(k) clearance granted on: July 25, 2023

Indication: Processing of diffusion-weighted MRI sequences into 3D maps that represent white matter tracts.

Available as: Automated radiological image processing software.

Overview: The Food and Drug Administration (FDA) has granted 510(k) clearance to a new software tool called Advanced Neuro Diagnostic Imaging (ANDI) (Imeka, Sherbrooke, Canada), which analyzes diffusion-weighted imaging (DWI) using artificial intelligence (AI) to map white matter in the brain. This technology also provides details about the microstructural makeup of the white matter and creates graphs showing differences between microstructural changes and normal values.

MOVEMENT DISORDERS

Lamzede (velmanase alfa-tycv; Chiesi Global Rare Diseases, Boston, MA)

Approval granted on: February 16, 2023

Indication: Treatment of non-central nervous system manifestations of alpha-mannosidosis (AM) in adult and pediatric patients.

Administration: The recommended dosage of Lamzede is 1 mg/kg (actual body weight) administered once every week as an intravenous infusion.

The total volume of infusion is determined by the patient’s actual body weight and should be administered over a minimum of 60 minutes for patients weighing up to 49 kg. Patients weighing 50 kg and greater should be infused at a maximum infusion rate of 25 mL/hour to control the protein load.

Boxed Warning: Lamzede’s label contains a boxed warning for hypersensitivity reactions, including anaphylaxis.

Overview: The Food and Drug Administration (FDA) approved Lamzede as the first enzyme replacement therapy in the United States to treat non-central nervous system symptoms associated with AM in adult and pediatric patients. Recommended dosage for Lamzede is 1 mg/kg (actual body weight) administered once weekly as an intravenous infusion. The prescribing information contains a Boxed Warning for severe hypersensitivity reactions; additional recommendations are for clinicians to verify that patients are not pregnant and to consider pretreatment with antihistamines, antipyretics, and/or corticosteroids.

Skyclarys (omaveloxolone; Reata Pharmaceuticals, Plano, TX)

Approval granted on: February 28, 2023

Indication: Skyclarys is indicated for the treatment of Friedreich’s ataxia in adults and adolescents aged 16 years and older.

Administration: Treatment of Friedreich ataxia in adults and adolescents aged 16 years and older.

Overview: The Food and Drug Administration (FDA) approved Skyclarys as the first therapy to treat Friedreich ataxia (FA) in adults and adolescents aged 16 years and older. Those who received Skyclarys improved by −1.63 ± 1.78 points on the Modified Friedreich’s Ataxia Rating Scale (mFARS), while those who received a placebo worsened by +2.52 ± 1.18 points on mFARS at week 48. In the Skyclarys cohort, participants noted an improvement in each component of the mFARS compared with the placebo cohort. The rates of adverse events in both cohorts were similar, with most common adverse events being mild to moderate in intensity. Patients who received Skyclarys were more likely to experience headaches, nausea, and increased alanine and aspartate aminotransferase (ALT and AST, respectively).

Daxxify (daxibotulinumtoxinA-lanm; Revance Therapeutics, Nashville, TN)

Approval granted on: September 8, 2022

Approval for expanded indication granted on: August 15, 2023

Indication: Treatment of cervical dystonia in adult patients.

Administration: The recommended dose of Daxxify for the treatment of cervical dystonia ranges from 125 Units to 250 Units given intramuscularly as a divided dose among affected muscles. In patients previously treated with another botulinum toxin, their past dose, response to treatment, duration of effect, and adverse event history should be taken into consideration when determining the initial Daxxify dose. A description of the average Daxxify dose and percentage of total dose injected into specific muscles in the pivotal clinical trials can be found in Section 14. Limiting the dose injected into the sternocleidomastoid muscle may reduce the occurrence of dysphagia.

Boxed Warning: Daxxify’s label contains a boxed warning for distant spread of toxin effect.

Overview: The Food and Drug Administration (FDA) has approved Daxxify for its first therapeutic indication for injection to treat cervical dystonia in adults. Daxxify was previously approved for injection to temporarily reduce the appearance of moderate to severe glabellar lines. Common treatment-related adverse events associated with Daxxify were dysphagia, muscular weakness, and injection site pain.

Ingrezza (valbenazine; Neurocrine Biosciences, San Diego, CA)

Approval granted on: April 11, 2017

Approval for expanded indication granted on: August 18, 2023

Indication: Treatment of adults with tardive dyskinesia; chorea associated with Huntington disease (HD).

Administration: Administer Ingrezza orally with or without food.

For chorea associated with HD:

The initial dosage for Ingrezza is 40 mg once daily. Increase the dose in 20 mg increments every two weeks to the recommended dosage of 80 mg once daily. A dosage of 40 mg or 60 mg once daily may be considered depending on response and tolerability.

Boxed Warning: Ingrezza’s label contains a boxed warning for depression and suicidal ideation and behavior in patients with Huntington’s disease.

Overview: Ingrezza has received approval from the Food and Drug Administration (FDA) for the treatment of adults with chorea associated with HD. The agent, delivered as a once-daily capsule, is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor also approved by the FDA for the treatment of adults with tardive dyskinesia. Chorea, a symptom associated with HD, is characterized by unpredictable, irregular movements. Common treatment-emergent adverse events (TEAEs) included somnolence, sedation, urticaria, rash, and insomnia.

MULTIPLE SCLEROSIS & AUTOIMMUNE DISORDERS

Tyruko (natalizumab-sztn; Sandoz, Basel, Switzerland)

Approval granted on: August 24, 2023

Indication: Monotherapy for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome (CIS), relapsing-remitting disease, and active secondary progressive disease, in adults.

Administration: The recommended dose of Tyruko for multiple sclerosis is 300 mg intravenous (IV) infusion over 1 hour every 4 weeks.

Boxed Warning: Tyruko’s label contains a boxed warning for progressive multifocal leukoencephalopathy.

Overview: Tyruko, a biosimilar of Tysabri (natalizumab; Biogen, Cambridge, MA) developed by Polpharma Biologics (Warsaw, Poland), has received Food and Drug Administration (FDA) approval to treat adults with relapsing forms of MS, including CIS, relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS). Tyruko, an integrin receptor antagonist, is administered as a 300 mg IV infusion once every 4 weeks.

NEUROMUSCULAR DISORDERS

Qalsody (tofersen; Biogen, Cambridge, MA)

Accelerated approval granted on: April 24, 2023

Indication: Treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with Qalsody. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).

Administration: Administer Qalsody intrathecally using a lumbar puncture by, or under the direction of, healthcare professionals experienced in performing lumbar punctures. The recommended dosage is 100 mg (15 mL) of Qalsody per administration. Initiate Qalsody treatment with 3 loading doses administered at 14-day intervals. Administer a maintenance dose every 28 days thereafter.

Overview: The Food and Drug Administration (FDA) approved the first treatment for ALS in adults who have a mutation in the SOD1 gene. Qalsody 100 mg/15 mL injection was approved under accelerated approval based on results of a study documenting reductions in plasma NfL levels seen in those treated with Qalsody. SOD1-ALS is an ultra-rare, fatal genetic disease affecting approximately 300 individuals in the United States. ATLAS, an ongoing phase 3 study, will continue as a confirmatory trial for Qalsody in people who are presymptomatic for SOD1-ALS.

There are important warnings and precautions associated with treatment with tofersen including myelitis and/or radiculitis; papilledema and elevated intracranial pressure; and aseptic meningitis. The most common adverse reactions reported in > 10% of participants treated with tofersen included pain, fatigue, arthralgia, cerebrospinal (CSF) white blood cell increase and myalgia.

Elfabrio (pegunigalsidase alfa-iwxj; Chiesi Global Rare Diseases, Boston, MA; Protalix Biotherapeutics, Carmiel, Israel)

Approval granted on: May 10, 2023

Indication: Treatment of adults with confirmed Fabry disease.

Administration: The recommended dosage of Elfabrio, based on actual body weight, is 1 mg/kg administered by intravenous infusion every 2 weeks. The initial recommended Elfabrio infusion rates for enzyme replacement therapy (ERT)–experienced or ERT-naïve patients are based on actual body weight.

Boxed Warning: Elfabrio’s label contains a boxed warning for hypersensitivity reactions including anaphylaxis.

Overview: The Food and Drug Administration (FDA) approved a new treatment for adult patients diagnosed with Fabry disease, sometimes referred to as “Anderson-Fabry disease”. Elfabrio represents a unique PEGylated, covalently crosslinked form of α-galactosidase A developed as ERT to treat individuals with Fabry disease. Treatment is administered as an intravenous infusion every 2 weeks. Data from clinical studies evaluating the drug’s safety and efficacy have demonstrated that Elfabrio provided noninferior efficacy in terms of controlling estimated glomerular filtration decline, a marker of kidney disease, compared with treatment with agalsidase beta.

Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc; Argenx SE, Amsterdam, Netherlands)

Approval granted on: June 20, 2023

Indication: Treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Administration: The recommended dosage of Vyvgart Hytrulo is 1,008 mg / 11,200 units (1,008 mg efgartigimod alfa and 11,200 units hyaluronidase) administered subcutaneously over approximately 30 to 90 seconds in cycles of once weekly injections for 4 weeks.

Overview: The Food and Drug Administration (FDA) approved Vyvgart Hytrulo, a drug that is injected subcutaneously to treat gMG in adult patients who test positive for AChR antibodies. The FDA approval was based upon results from the phase 3 ADAPT-SC clinical trial (NCT04735432), which demonstrated Vyvgart Hytrulo’s efficacy in reducing anti-AChR antibody concentrations with noninferiority (P<.0001) compared to intravenous Vyvgart (efgartigimod alfa-fcab, Argenx SE, Amsterdam, Netherlands). Both Vyvgart Hytrulo and Vyvgart were designed to bind to the neonatal Fc receptor (FcRn) to reduce circulation of human immunoglobulin G (IgG) in the blood. Anti-AChR antibodies, present in around 85% of the patient population, are a type of IgG that disrupt AChR, causing muscle weakness.

Elevidys (delandistrogene moxeparvovec-rokl; Sarepta Therapeutics, Cambridge, MA)

Accelerated approval granted on: June 22, 2023

Indication: Treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene.

Administration: Elevidys is administered as an intravenous infusion.

The recommended dose of Elevidys is 1.33 × 10¹⁴ vector genomes per kilogram (vg/kg) of body weight (or 10 mL/kg body weight).

Overview: Through its Accelerated Approval Pathway, the Food and Drug Administration (FDA) has approved Elevidys to treat pediatric patients with DMD aged 4 to 5 years who are ambulatory and have a confirmed mutation in the DMD gene. The approval is based on data from a phase 1/2 clinical trial of 4 participants (NCT03375164), a phase 1 clinical trial of 46 participants called ENDEAVOR (NCT04626674), and a phase 2 clinical trial of 41 participants (NCT03769116).

Rystiggo (rozanolixizumab-noli; UCB, Atlanta, GA)

Approval granted on: June 26, 2023

Indication: Treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

Administration: The recommended dosage of Rystiggo is based on body weight. Administer the recommended dosage as a subcutaneous infusion using an infusion pump at a rate of up to 20 mL/hour once weekly for 6 weeks.

Overview: The Food and Drug Administration (FDA) has approved Rystiggo as a subcutaneous infusion for the treatment of adults with gMG who are AChR or MuSK antibody positive based on findings published in The Lancet Neurology. Rystiggo was under Priority Review with the FDA and was approved based on safety and efficacy data from the pivotal phase 3 MycarinG clinical study (NCT03971422). The most commonly reported adverse reactions were headache, diarrhea, infections, pyrexia, nausea, and hypersensitivity reactions. Rystiggo, a humanized IgG4 monoclonal antibody targeting the neonatal Fc receptor (FcRN), is currently the only FDA-approved treatment for the MuSK- or AChR-antibody positive subtypes of gMG.

Pombiliti (cipaglucosidase alfa-atga; Amicus Therapeutics, Philadelphia, PA) + Opfolda (miglustat; Amicus Therapeutics, Philadelphia, PA)

Approval granted on: September 28, 2023

Indication: Pombiliti is indicated, in combination with Opfolda, for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT).

Administration: The recommended dosage of Pombiliti is 20 mg/kg (of actual body weight) administered every other week as an intravenous infusion over approximately 4 hours. Start Pombiliti in combination with Opfolda 2 weeks after the last ERT dose. Initiate the Pombiliti infusion approximately 1 hour after oral administration of Opfolda. If the Pombiliti infusion cannot be started within 3 hours of oral administration of Opfolda, reschedule Pombiliti in combination with Opfolda at least 24 hours after Opfolda was last taken. If Pombiliti in combination with Opfolda are both missed, re-start treatment as soon as possible.

Boxed Warning: Pombiliti’s label contains a boxed warning for hypersensitivity reactions including anaphylaxis, infusion-associated reactions, and risk of acute cardiorespiratory failure in susceptible patients.

Opfolda (miglustat; Amicus Therapeutics, Philadelphia, PA)

Approval granted on: September 28, 2023

Indication: Opfolda is indicated, in combination with Pombiliti, for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40 kg and who are not improving on their current enzyme replacement therapy (ERT).

Administration: The recommended dosage of Opfolda is based on actual body weight. For patients weighing:

≥50 kg, the recommended dosage is 260 mg orally every other week.

≥40 kg to <50 kg, the recommended dosage is 195 mg orally every other week.

Start Opfolda in combination with Pombiliti 2 weeks after the last ERT dose. Take Opfolda approximately 1 hour before intravenous (IV) administration of Pombiliti. Swallow the Opfolda capsules whole only with unsweetened beverages (eg, water, tea or coffee with no cream, sugar, or sweeteners). Do not consume other beverages or food for at least 2 hours prior to and 2 hours after administration of Opfolda.

Overview: The Food and Drug Administration (FDA) has approved Pombiliti + Opfolda combination therapy for people with late-onset Pompe disease (LOPD) who weigh at least 40 kg and are not improving on current ERT. Pombiliti + Opfolda will be distributed and marketed in the United States by Amicus Therapeutics, Philadelphia, PA. Pombiliti + Opfolda therapy should be started 2 weeks after the last ERT dose. Pombiliti has a recommended dosage of 20 mg/kg administered every other week as an IV infusion over 4 hours. Pombiliti therapy must be preceded by oral administration of Opfolda (available in 65 mg capsules) approximately 1 hour before IV infusion. Pombiliti’s label contains a boxed warning for hypersensitivity reactions including anaphylaxis, infusion-associated reactions, and risk of acute cardiorespiratory failure in susceptible patients.

Zilbrysq (zilucoplan; UCB, Atlanta, GA)

Approval granted on: October 17, 2023

Indication: Treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Administration: The recommended dosage of Zilbrysq is given once daily as a subcutaneous injection and is dependent on actual body weight.

Boxed Warning: Zilbrysq’s label contains a boxed warning for serious meningococcal infections.

Overview: The Food and Drug Administration (FDA) has approved Zilbrysq as a treatment for gMG in adults who are anti-AChR Ab+. Zilbrysq is the first approved once-daily subcutaneous, targeted complement component 5 (C5) inhibitor for gMG and is self-administered. In anti-AChR Ab+ gMG, complement C5 mediates damage to the neuromuscular junction (NMJ), leading to skeletal muscle weakness. Treatment-emergent adverse events (TEAEs) occurred in 77% of participants treated with Zilbrysq. The most common reported TEAEs were injection-site bruising, headache, diarrhea, and worsening of disease.

Agamree (vamorolone; Catalyst Pharmaceuticals, Coral Gables, FL)

Approval granted on: October 26, 2023

Indication: Treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older.

Administration: The recommended dosage of Agamree is 6 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 300 mg for patients weighing more than 50 kg. Some patients may respond to a dose of 2 mg/kg daily. Doses may be titrated down to 2 mg/kg/day as needed, based on individual tolerability.

Overview:Agamree has received Food and Drug Administration (FDA) approval as an oral suspension 40 mg/mL to treat DMD in patients aged 2 years and older. Agamree was developed by Santhera Pharmaceuticals (Pratteln, Switzerland) and is a first-in-class medication that binds to the same receptors as corticosteroids and modifies their downstream activity.

Wainua (eplontersen; AstraZeneca, Cambridge, UK; Ionis Pharmaceuticals, Carlsbad, CA)

Approval granted on: December 21, 2023

Indication: Treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) in adults.

Administration: The recommended dosage of Wainua is 45 mg administered by subcutaneous injection once monthly.

Overview: Wainua has been approved by the Food and Drug Administration (FDA) as a treatment for hereditary amyloid transthyretin amyloidosis polyneuropathy in adults. Wainua is a ligand-conjugated antisense (LICA) medication that inhibits the production of the transthyretin (TTR) protein and is administered by auto-injector.

SLEEP

Wesper Lab (Wesper, New York, NY)

510(k) clearance granted on: March 9, 2023

Indication:Recording of multiple physiological parameters from a sleeping patient for the purpose of simultaneous or subsequent display of the parameters.

Available as: Sleep ventilatory effort recorder

Overview: Wesper announced that its wearable sleep monitoring platform has received an additional Food and Drug Administration (FDA) clearance for the ongoing collection of physiologic and environmental data associated with sleep over multiple nights in response to therapeutic interventions. Wesper previously had received clearance for its wearable sleep monitoring platform to provide data associated with sleep to aid clinicians in the diagnosis of sleep apnea. The Wesper platform consists of patches to be applied by patients along with a pulse oximeter which provide data wirelessly to clinicians, an app that can be used by patients to access data on sleep outcomes and which can be used by individuals to log additional personal and lifestyle factors that may affect sleep, and a portal that can be used by clinicians to communicate with patients, generate reports, and make adjustments to sleep treatments. Data collected by the Wesper platform include sleep position, heart rate, sleep duration, SpO2, airflow, pressure, snoring, and more.

Lumryz (sodium oxybate; Avadel Pharmaceuticals, Dublin, Ireland)

Approval granted on: May 1, 2023

Indication: Treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy.

Administration: The recommended starting dosage is 4.5 g once per night administered orally. Increase the dosage by 1.5 g per night at weekly intervals to the recommended dosage range of 6 g to 9 g once per night orally. The dosage may be gradually titrated based on efficacy and tolerability. Doses higher than 9 g per night have not been studied and should not ordinarily be administered.

Boxed Warning: Lumryz’s label contains a boxed warning for central nervous system (CNS) depression and abuse and misuse.

Overview: The Food and Drug Administration (FDA) has granted approval for an extended-release formulation of the CNS depressant Lumryz to treat cataplexy or excessive daytime sleepiness in adults with narcolepsy. This extended-release formulation is meant to be taken at bedtime. According to company statements, product availability is expected in June 2023. In addition, Orphan Drug Exclusivity was granted for the drug beginning in 2023 and ending in 2030 based on data indicating the extended-release formulation to be more effective than currently marketed sodium oxybate products taken twice nightly.

SOMNUM (HoneyNaps, Seoul, South Korea)

510(k) clearance granted on: August 16, 2023

Indication: Analysis (automatic scoring and manual re-scoring), display, redisplay (retrieve), summarize and reports generation of digital data collected by monitoring devices typically used to evaluate sleep and respiratory related sleep disorders.

Available as: Automatic event detection software for polysomnograph with electroencephalograph.

Overview: HoneyNaps announced that the Food and Drug Administration (FDA) has granted the company 510(k) clearance to market SOMNUM (HoneyNaps, Seoul, South Korea) in the United States. SOMNUM is a deep learning artificial intelligence (AI)-based algorithm that analyzes sleep biosignal data obtained from polysomnography records in real-time to provide information to health care providers, assisting in the diagnosis of sleep and respiratory-related sleep disorders in adults.

STROKE

Brainomix 360 e-ASPECTS (Brainomix, Oxford, UK)

510(k) clearance granted on: February 23, 2023

Indication: Assessment and characterization of brain tissue abnormalities using CT image data.

Available as:Computer-assisted diagnostic software.

Overview: Brainomix 360 e-ASPECTS, a computer-assisted diagnostic software device, has received clearance by the Food and Drug Administration (FDA) to assist clinicians in assessing and categorizing abnormal non-contrast CT scans of the brain. This software device, which is cleared for use in patients with middle cerebral artery or internal carotid artery occlusion, analyzes CT image data with artificial intelligence software to produce a single ASPECTS (Alberta Stroke Program Early CT Score) score which can be modified by a clinician, if needed. The device also extracts individual voxel data from images to create a “heat map” of hypodense regions to assist with clinical assessment of ischemic brain tissue injury. According to the 510(k) summary of safety and effectiveness, use of the Brainomix 360 e-ASPECTS device provides a comparative analysis to traditional standard of care radiologic assessment using ASPECTS.

Rapid NCCT Stroke (RapidAI, Menlo Park, CA)

510(k) clearance granted on: March 2, 2023

Indication: Analysis of nonenhanced head CT (NCCT) images to assist hospital networks and trained clinicians in workflow triage by flagging and communicating suspected positive findings of (1) head CT images for Intracranial Hemorrhage (ICH) and (2) NCCT large vessel occlusion (LVO) of the ICA and MCA-M1.

Available as: Radiological computer-assisted triage and notification software.

Overview: RapidAI (Menlo Park, CA), a developer of neurovascular and vascular artificial intelligence (AI)–enhanced clinical decision support and patient workflow solutions, announced it has received Food and Drug Administration (FDA) 510(k) clearance for Rapid NCCT Stroke.

According to the company, Rapid NCCT Stroke uses AI to analyze noncontrast CT (NCCT) images to detect suspected intracranial hemorrhage and large vessel occlusion of the distal internal carotid artery and middle cerebral artery. The fully automated system then delivers triage and prioritization notifications through picture archiving and communication systems, email, and the Rapid mobile app.

Annalise Enterprise CTB Triage Trauma (Annalise.AI, Sydney, Australia)

510(k) clearance granted on: April 3, 2023

Indication: Triage and prioritization of studies with features suggestive of the following findings: acute subdural/epidural hematoma; acute subarachnoid hemorrhage; intra-axial hemorrhage; intraventricular hemorrhage.

Available as:Radiological computer-assisted triage and notification software.

Overview: Annalise.ai, a company which develops artificial intelligence (AI) applications for use with medical imaging, announced that it had received additional clearances by the Food and Drug Administration (FDA) for its computer-aided triage and notification devices (CADt). These clearances were for CT brain findings for the following conditions:

• Acute subdural/epidural hematoma
• Acute subarachnoid hemorrhage
• Intra-axial hemorrhage
• Intraventricular hemorrhage

Additional clearances were received by the company for use in chest radiographs with findings of suspected pneumothorax, tension pneumothorax, pleural effusion, pneumoperitoneum, and vertebral compression fracture. According to details provided by the FDA, “CADt are software devices intended to aid in prioritization and triage of time-sensitive suspected findings based on the analysis of radiologic exams.” These software devices rely on deep learning to identify and flag potential pathologies within radiologic images. The FDA cautions that such devices are to be used to flag specific radiologic images and are not a substitute for physician review and interpretation of such images. CADt are not diagnostic devices but rather prioritization and triage tools.

Millipede 070 Aspiration Catheter (Perfuze, Galway, Ireland

510(k) clearance granted on: October 18, 2023

Indication: The Millipede 070 Aspiration Catheter, with the Perfuze Aspiration Tube Set and a compatible aspiration pump, is indicated for use in the revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (within the internal carotid, middle cerebral - M1 and M2 segments, basilar and vertebral arteries) within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment.

Available as: Thrombus retriever catheter.

Overview: Perfuze announced that the second generation of its Millipede 088 access catheter and its Millipede 070 aspiration catheter have received Food and Drug Administration (FDA) 510(k) clearance. The Galway, Ireland-based medical device company is developing technology to treat acute ischemic stroke.

The Millipede 070 aspiration catheter is intended for the rapid, safe removal of clots. The company designed the device to provide superior deliverability and high procedural efficiency. The device’s rib-and-recess surface architecture is intended to improve navigability and reduce tip stiffness while maintaining durability.

Millipede 088 Access Catheter (Perfuze, Galway, Ireland)

510(k) clearance granted on: December 14, 2023

Indication: Facilitating the insertion and guidance of microcatheters into a selected blood vessel in the neurovasculature.

Available as: Neurovascular percutaneous catheter.

Overview: Perfuze announced that the second generation of its Millipede 088 access catheter and its Millipede 070 aspiration catheter have received Food and Drug Administration (FDA) 510(k) clearance. The Galway, Ireland-based medical device company is developing technology to treat acute ischemic stroke.

According to Perfuze, the Millipede 088 device, which initially received FDA clearance in 2022, facilitates the safe insertion and guidance of microcatheters for neurointerventional or diagnostic procedures. It first received European CE Mark approval in 2021.