Ionis Pharmaceuticals Receives FDA Breakthrough Therapy Designation for ION582 in Angelman Syndrome Treatment

Ionis Pharmaceuticals has received FDA Breakthrough Therapy designation for ION582 in Angelman syndrome, a rare neurological disease. The designation is based on Phase 1/2 HALOS study results showing clinical improvement in communication, cognition, and motor function, as well as favorable safety and tolerability. Ionis initiated a global Phase 3 REVEAL study earlier this year to enroll children and adults with AS.

Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) has received a significant milestone in its quest to treat Angelman syndrome (AS), a rare neurological disease. The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to ION582, an investigational RNA-targeted antisense medicine [1]. This designation is based on promising results from the Phase 1/2 HALOS study, which demonstrated consistent and encouraging clinical improvement in communication, cognition, and motor function, along with favorable safety and tolerability [1].

Angelman syndrome is a rare genetic disorder affecting approximately 1 in 21,000 people worldwide. It is characterized by profound intellectual disability, balance issues, motor impairment, and debilitating seizures. Currently, there are no approved disease-modifying therapies for the condition [1]. The Breakthrough Therapy designation aims to expedite the review process for medicines that treat serious or life-threatening conditions and show preliminary evidence of substantial improvement over existing therapies [1].

Ionis initiated the global Phase 3 REVEAL study (NCT06914609) earlier this year to enroll children and adults with AS who have a maternal UBE3A gene deletion or mutation [1]. This study is anticipated to enroll participants and provide further data to support the potential of ION582 as a treatment for AS.

About ION582
ION582 is designed to inhibit the expression of the UBE3A antisense transcript (UBE3A-ATS) and increase the production of UBE3A protein, which is implicated in the pathogenesis of Angelman syndrome. The FDA and European Medicines Agency (EMA) have granted Orphan Drug designation to ION582, and the FDA has also granted Fast Track and Rare Pediatric designations [1].

Ionis Pharmaceuticals has a robust history in developing leading neurological disease medicines, including SPINRAZA® (nusinersen) for spinal muscular atrophy and WAINUA® (eplontersen) for hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) [1]. The company's clinical-stage portfolio includes 13 investigational medicines, eight of which are wholly owned by Ionis [1].

References:
[1] https://www.stocktitan.net/news/IONS/ionis-receives-u-s-fda-breakthrough-therapy-designation-for-ion582-7ony8ist94z1.html
[2] https://www.businesswire.com/news/home/20250909085802/en/Ionis-receives-U.S.-FDA-Breakthrough-Therapy-designation-for-ION582-in-Angelman-syndrome