Cerliponase Alfa Approved for All Ages of CLN2 Disease, SAGE-324 Discontinued, ION582 to Advance to Phase 3 in Angelman Syndrome

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.
According to an announcement from BioMarin Pharmaceutical, the FDA has approved an expanded indication for cerliponase alfa (Brineura), a therapy for children with neuronal CLN2 disease) or Batten disease, to treat patients of all ages, including those younger than 3. In addition, the therapy will now be available to all patients, including those who are symptomatic or asymptomatic. CLN2 disease, also known as TPP1 deficiency, typically starts with seizures between the ages of 2 and 4 years old, preceding in the majority of cases by language development delay. Cerliponase alfa, a recombinant human form of tripeptidyl peptidase 1 enzyme, was the first approved treatment for forms of Batten disease, such as CLN2 disease. Its original approval, which came in 2017, included those older than 3 years of age with the disease.

Newly announced data from the phase 2 KINETIC 2 study (NCT05173012) showed that treatment with investigational SAGE-324, also known as BIIB124, did not demonstrate statistically significant results on the study’s primary end point in participants with essential tremor (ET). As a result of these data, Biogen and Sage Therapeutics, the drug manufacturers, have decided to close the open-label safety study and terminate the development of SAGE-324 as a treatment for ET. The trial featured 147 patients with ET who were randomly assigned to either placebo or SAGE-324 in doses of 15 mg, 30 mg, and 60 mg for a 3-month period. After 91 days of treatment, the investigational agent failed to distinguish itself from placebo on the primary end point of change in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale (PS) Item 4 (upper limb) total score.

Newly announced data from a multiple-ascending dose (MAD) portion of the open-label, phase 1/2 HALOS study (NCT05127226) showed a resounding number of individuals with Angelman syndrome who had improvements in overall symptoms following treatment with investigational ION582. Ionis Pharmaceuticals, the drug manufacturers of ION582, announced it will initiate phase 3 studies testing the agent in the first half of 2025. At the final timepoint of the completed MAD portion of the study at 6 months, 97% of the 51-patient cohort showed clinically meaningful improvement on the Symptoms of Angelman Syndrome-Clinician Global Impression of Change (SAS-CGI-C) scale, an outcome of Angelman syndrome symptoms. ION582, an antisense oligonucleotide designed to inhibit the expression of the UBE3A antisense transcript, was considered safe and tolerable at all dose levels.

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