2024 ASF Family Conference – Pharma and Biotech Industry Update

Quick Overview

The 2024 ASF Family Conference featured updates on trials for Angelman Syndrome treatments by Ultragenyx and Ionis Pharmaceuticals. Kim Goodspeed from Ultragenyx discussed the GTX-102 trial, highlighting its Phase 1/2 open-label study for deletion-type Angelman syndrome. The trial showed promising improvements in cognition and communication, though it was noted that all participants knew they were receiving treatment, which could influence results. Safety concerns, such as lower extremity weakness, were addressed with protocol adjustments.

Becky Crean and Dr. Lynne Bird from Ionis presented the HALOS trial for ION582, an ASO designed to unsilence the paternal UBE3A gene. The trial included a broad demographic and showed favourable safety and efficacy results, with significant improvements in communication and cognition. Both companies plan to advance to Phase 3 trials, aiming to confirm the efficacy and safety of their treatments for broader Angelman syndrome populations. The conference underscored the collaborative effort and commitment of families and researchers in advancing treatment options.

The 2024 ASF Family Conference provided a platform for significant updates from the pharmaceutical and biotech industries, focusing on advancements in treatments for Angelman syndrome. The conference featured presentations from Kim Goodspeed of Ultragenyx and Becky Crean and Lynne Bird from Ionis Pharmaceuticals, each sharing insights into their respective clinical trials and future plans.

Ultragenyx’s GTX-102 Trial

Kim Goodspeed, a child neurologist from Ultragenyx, presented data from their Phase 1/2 open-label study of GTX-102, an investigational drug aimed at treating Angelman syndrome. The study focused on patients with deletion type Angelman syndrome, aged 4 to 18 years. Goodspeed emphasised the importance of understanding the preliminary nature of the data, as the trial was not controlled, meaning all participants knew they were receiving the treatment.

The trial aimed to unsilence the paternal UBE3A gene using an antisense oligonucleotide (ASO), potentially addressing the genetic cause of Angelman syndrome. The study showed promising results, with improvements in cognition, communication, and behaviour, as measured by various assessments like the Bayley cognition score. Caregiver feedback highlighted real-world impacts, such as increased focus and engagement in children.

Safety was a key focus, with initial concerns about lower extremity weakness in some patients. However, after protocol adjustments, the incidence of this adverse event was significantly reduced. The next step is a Phase 3 study, set to begin by the end of the year, which will be a double-blinded, randomised, sham-controlled trial to further assess the drug’s efficacy and safety.

Ionis Pharmaceuticals’ HALOS Trial

Becky Crean and Lynne Bird from Ionis Pharmaceuticals discussed the HALOS trial, which investigates ION582, another ASO designed to treat Angelman syndrome by unsilencing the paternal UBE3A gene. The trial is global and open-label, including a broad range of participants aged 2 to 50, with both deletion and mutation subtypes.

The trial’s primary goal is to assess safety and tolerability, with secondary measures focusing on key functional areas affected by Angelman syndrome, such as communication and cognition. The first part of the trial, involving three different doses, showed promising results, with significant improvements in receptive and expressive communication, cognition, and overall symptoms.

The safety profile of ION582 was favourable, with no reports of leg weakness or other serious adverse events. The trial will continue with a long-term extension, and plans for a Phase 3 pivotal trial are underway, with discussions with the FDA expected by the end of the year.

Conclusion

Both Ultragenyx and Ionis Pharmaceuticals are making strides in developing treatments for Angelman syndrome, with their respective ASO therapies showing potential in early trials. The conference highlighted the importance of continued research and collaboration between families, researchers, and pharmaceutical companies to advance treatment options for this rare genetic disorder. As these trials progress, the hope is to bring effective therapies to market, improving the quality of life for individuals with Angelman syndrome and their families.