Tividenofusp Alfa to be Submitted for Hunter Syndrome, Transcranial Stimulation Shows Efficacy in Alzheimer's, FDA Approves Pre-Filled Syringe for Efgartigimod

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

According to a recent announcement, Denali Therapeutics has begun initiating its biologics license application (BLA) submission of tivi-denofusp alfa, an investigational agent, as a potential treatment for Hunter syndrome, otherwise known as MPS II. The submission, expected to be complete by May 2025, will be through the accelerated approval pathway, using change in cerebrospinal fluid heparan sulfate (CSF HS) as a surrogate end point to support approval. Hunter syndrome, a rare genetic disorder impacting more than 2000 people globally, has traditionally been managed with symptomatic treatments such as enzyme replacement therapy (ERT). Tividenofusp alfa (DNL310) is a novel therapeutic that combines the iduronate 2-sulfatase (IDS) enzyme with Denali’s proprietary Enzyme Transport technology to deliver IDS throughout the brain and body, aiming to address the behavioral, cognitive, and physical manifestations of the disease. To date, the agent has received fast track and breakthrough therapy designations by the FDA, recognizing it as a promising therapeutic.

Newly announced findings from a 52-week, phase 2 study (NCT05454540) showed that personalized treatment with transcranial magnetic stimulation (rTMS) of the precuneus (PC) may slow down the impairment of cognitive functions, activities of daily living, and behavioral disturbances in patients with mild-to-moderate Alzheimer disease (AD). Overall, the study met its primary end point, with treated patients demonstrating a significant effect on the primary end point of change in Clinical Dementia Rating-Sum of Boxes (CDR-SB). Published in Alzheimer’s Research & Therapy, the trial featured 48 patients with mild-to-moderate AD testing the effects of the SinaptiStim System, a novel approach using non-invasive personalized precision neuromodulation. Calibrated to each individual’s brain, the treatment is delivered in weekly sessions in a recliner ranging from 20 minutes with the first-generation system to 6 months with the second-generation system. In the study, patients underwent a 2-week intensive course where rTMS (or sham) was applied over the PC daily, followed by a 50-week maintenance phase in which the same stimulation as applied once weekly.

The FDA has approved a new pre-filled syringe administration route for efgartigimod (Vyvgart; Argenx), a marketed medication for generalized myasthenia gravis (gMG) and chronic inflammatory demyelinating polyneuropathy (CIDP). With the decision, it offers patients greater convenience and flexibility, allowing in-home administration and reducing the number of time-consuming trips that typically come with intravenous (IV) infusions. A phase 1, randomized, open-label, parallel-group, single-dose, bioequivalence study tested the effects of SC efgartigimod, known as Vyvgart Hytrulo, via a pre-filled syringe against a vial + syringe presentation in healthy participants. Featuring 120 healthy adults aged at least 55, the study provided data supporting the efficacy, safety, and bioequivalence of the SC prefilled syringe administration route for efgartigimod.

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