Ionis prepares for Phase III trial of Angelman syndrome drug

Ionis Pharmaceuticals is gearing up to start Phase III development of ION582 for Angelman syndrome (AS) in the first half of 2025. This decision follows the release of promising detailed results from the mid-stage HALOS study. The experimental antisense oligonucleotide demonstrated significant benefits in communication, cognition, and motor function across a wide patient population.

After six months, 97% of patients in the medium- and high-dose groups showed clinically meaningful improvements in overall symptoms of the rare genetic neurological disorder. This was measured using the SAS-CGI-C scale, which assesses clinicians' impressions of AS symptoms. Additionally, the Bayley-4, an objective clinician-administered assessment of clinical functioning, revealed that 67% of participants improved in cognition, 67% in receptive communication, 69% in expressive communication, 46% in gross motor skills, and 72% in fine motor function. Improvements were also noted in key functional areas using the Vineland-3 and ORCA parent-reported assessment tools.

These results expand on the topline data announced in May, which led Ionis to continue developing ION582 independently after its long-standing partner, Biogen, decided not to license the drug. At that time, Baird analysts viewed Ionis' topline data favorably for Ultragenyx, a significant competitor in the Angelman syndrome market with its antisense oligonucleotide GTX-102. They noted that Biogen's decision removes potential commercial competition backed by substantial resources, which might positively affect Ultragenyx's position in the Angelman syndrome space.

In May, Ultragenyx reported early data on GTX-102. Baird analysts noted that cross-trial comparisons seemed to favor Ultragenyx's drug over ION582. Approximately 83% of patients showed improvements on Bayley-4 cognition measures, and around 75% exhibited improvements in receptive and/or expressive communication by day 170 in cohorts A and B of the Ultragenyx study. They added that GTX-102 appears to be the more effective option and suggested that the low rate of transient lower limb extremity weakness associated with GTX-102 should be tolerable given its greater efficacy in this rare disease context.

Ultragenyx recently announced that it had successfully aligned with the FDA on its Phase III study design for GTX-102. The company plans to begin its trial by the end of this year.