Throughout 2024, the neurology field witnessed significant advancements, ranging from novel therapeutic approaches to innovative trial designs. Key findings presented at major conferences are shaping the future of neurological care.
Enhanced Donanemab Titration Reduces ARIA-E
An enhanced titration dosing regimen of donanemab (Kisulna; Eli Lilly), an antiamyloid treatment, significantly reduced the frequency and severity of amyloid-related imaging abnormalities-edema (ARIA-E). The phase 3b TRAILBLAZER-ALZ-6 trial (NCT05738486) demonstrated that the titrated dosing regimen not only resulted in numerically lower ARIA-E at 24 weeks but also maintained sufficient amyloid reduction. This suggests a safer approach to amyloid-targeting therapy in Alzheimer's disease.
Simvastatin Fails to Show Benefit in SPMS
The phase 3 MS-STAT2 trial (NCT03387670) evaluated simvastatin in patients with non-active progressing secondary progressive multiple sclerosis (SPMS). While the treatment was safe and well-tolerated, it failed to demonstrate a reduction in disability progression rates. Further analyses are planned to explore secondary outcomes, fluid biomarkers, and MRI data.
Anti-Tau Agent E2814 Shows Promise in Early Alzheimer's
E2814 (Eisai), an investigational anti-tau therapeutic antibody, showed a significant effect on both early and late tau biomarkers in patients with dominantly inherited Alzheimer disease (DIAD). Data from the open-label, phase 1b/2 study E2814-G000-103 (NCT04971733) indicated that E2814's effects are specific to those with tau pathology, supporting its clinical development. The agent did not affect phosphorylated tau (p-tau)217 or MTBR-tau243 levels in healthy volunteers.
SynAIRgy Trial for Obstructive Sleep Apnea
The phase 3 SynAIRgy trial (NCT05813275) is evaluating the efficacy and safety of AD109 (Apnimed), a combination of antimuscarinic aroxybutynin and atomoxetine, for obstructive sleep apnea (OSA). AD109, a first-in-class once-daily medication, targets key neurological pathways in OSA to activate upper airway dilator muscles, maintaining an open airway during sleep.
DMTs May Halt Sleep-Related Disordered Breathing in SMA
Early treatment with a disease-modifying therapy (DMT) may interrupt the development of sleep-related disordered breathing and delay the initiation of ventilatory support in patients with spinal muscular atrophy (SMA). A small-scale study suggests further research is needed to understand the relationship between these medications and sleep-related respiratory outcomes in pediatric patients with SMA type 1.
KYSA-6 Trial of CAR-T Therapy in Myasthenia Gravis
The multicenter, open-label, phase 2 KYSA-6 trial (NCT06193889) will investigate the efficacy and safety of KYV-101 (Kyverna Therapeutics), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with refractory generalized myasthenia gravis (gMG). The trial will enroll 20 patients, with change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) as the primary efficacy end point.
Liraglutide Shows Protective Effects in Alzheimer's Disease
Treatment with liraglutide (Novo Nordisk), a glucagon-like peptide 1 (GLP-1) receptor agonist, has demonstrated neuroprotective effects against Alzheimer disease (AD) dementia. Research from a phase 2b study presented at the 2024 Alzheimer’s Association International Conference (AAIC) highlights the potential of GLP-1 analogues in AD treatment.
AB-1005 Gene Therapy for Parkinson's Shows Promising Results
Data from a phase 1b study (NCT04167540) assessing AskBio’s gene therapy AB-1005 in patients with Parkinson disease (PD) showed that the therapy met its primary end point of successful putamen coverage and was safe over an 18-month period. The small-scale study, including both mild (n = 6) and moderate (n = 5) forms of PD, experienced improvements in ON and OFF time with AB-1005.
Tolebrutinib Slows Disability Progression in nrSPMS
Results from the phase 3 HERCULES trial (NCT04411641) revealed that tolebrutinib (Sanofi), a Bruton’s tyrosine kinase (BTK) inhibitor, had a significant effect on disability accumulation compared with placebo in patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS). This trial marks the first to show a significant slowing of disability progression in this patient population.
TIMELESS Trial Assesses Tenecteplase in Late Stroke Window
Data from the TIMELESS trial (NCT03785678) indicated that tenecteplase, administered between 4.5 to 24 hours after stroke in patients with occlusions of the middle cerebral artery or internal carotid artery, did not result in better clinical outcomes than placebo. However, certain subgroups showed greater benefit, marking the first study to suggest intravenous (IV) thrombolytics could be given up to 24 hours without increased brain hemorrhage.
