Federal Drug Administration take steps to bolster the progress of Ionis Therapy's drug ION582
In a significant development for the rare disease community, Ionis Pharmaceuticals has announced the launch of the Phase 1/2a HALOS clinical trial (NCT05127226) for ION582, an investigational treatment for Angelman syndrome. This trial, which is ongoing, aims to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of ION582 in children and adults with Angelman syndrome.
The FDA has granted both Orphan Drug and Rare Pediatric Disease Designations to ION582, reflecting the urgent need for an effective treatment for this debilitating condition. These designations encourage the development of therapies for rare diseases and offer benefits such as FDA fee exemptions, financial incentives, and seven years of market exclusivity if approved. The European Medicines Agency (EMA) has also granted Orphan Drug designation to ION582.
Angelman syndrome is a rare genetic disorder that primarily affects individuals from birth to age 18. It is characterised by severe intellectual disability, speech impairment, and frequent seizures. In Angelman syndrome, mutations in the maternal copy of the UBE3A gene prevent a working UBE3A protein from being made, with only the maternal copy active in certain areas of the brain.
ION582 is designed to "turn on" the paternal copy of the UBE3A gene in Angelman syndrome, which is often "silenced" by Ubiquitin Protein Ligase E3A-Antisense Transcript (UBE3A-ATS). In preclinical studies, the blocking of UBE3A-ATS by ION582 effectively "turns on" the silenced paternal UBE3A gene.
The open-label study will assess the safety and tolerability of ascending doses of ION582 injected directly into the spinal canal in 44 patients, ages 2 to 50, enrolled in the trial. Recruitment for the HALOS trial is ongoing at two sites: Rush University Medical Center, in Chicago, and the University of North Carolina at Chapel Hill School of Medicine, in North Carolina.
C. Frank Bennett, PhD, executive vice president, chief scientific officer, and franchise leader for neurological programs at Ionis, stated that the FDA orphan drug designation for ION582 reflects the important and urgent need for delivering an effective treatment to patients living with Angelman syndrome. Ionis Pharmaceutical is committed to working closely with regulators, clinical investigators, patients, and caregivers to advance this novel treatment and make it available to those who need it.
If ION582 is approved, the FDA Rare Pediatric Disease Designation voucher program allows Ionis to request priority review for a subsequent experimental medication. This could expedite the development and approval of additional treatments for Angelman syndrome and other rare pediatric diseases.
The HALOS trial is a significant step forward in the quest for a treatment for Angelman syndrome. The results of this study could provide valuable insights into the safety, efficacy, and potential benefits of ION582 for patients with this rare and debilitating condition.
