Ionis announces positive topline results from Phase 1/2a trial...

Ionis announces positive topline results from Phase 1/2a trial of ION582 for Angelman syndrome:

• ION582 demonstrated consistent improvements across multiple functional domains in Angelman syndrome patients
• ION582 was safe and well tolerated at all dose levels
• Ionis plans to move ION582 into pivotal trial
• Detailed ION582 data to be presented at upcoming medical meeting

CARLSBAD, Calif., May 16, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced positive topline data from the HALOS Phase 1/2a open-label study of ION582 in Angelman syndrome. ION582 was safe and well tolerated in the study and showed encouraging and consistent benefits in individuals living with Angelman syndrome, with the most robust improvements observed in key areas of functioning including cognition, communication and motor function.
Ionis also announced that it will independently advance ION582 as part of Ionis' leading portfolio of potentially transformational medicines for serious neurological diseases. Ionis plans to review the ION582 Phase 1/2a results with regulatory authorities to align on the design of the pivotal program. Biogen has elected not to exercise its option to license ION582.
"There are currently no approved treatments for Angelman syndrome, which causes developmental delays, cognitive impairment and severe communications challenges, with most individuals unable to speak or live independently," said Lynne Bird, M.D., professor of clinical pediatrics at UC San Diego and HALOS study investigator. "We are encouraged by the positive and consistent improvements seen in the HALOS study across multiple measures, as these functional improvements could have a transformative impact in the lives of people living with Angelman syndrome and their caregivers. We are also encouraged by the favorable safety and tolerability profile observed in the study, which is particularly important when treating children. We very much look forward to further evaluation of ION582 in a pivotal program.

Part 1 of the HALOS trial was a three-month, multiple-ascending dose (MAD) study in 51 patients aged 2-50, which evaluated three doses of ION582. All eligible patients transitioned into the Part 2 long-term extension (LTE) portion of the study, which is evaluating the two higher doses of ION582 for an additional 12 months. Part 3 of the study will evaluate eligible patients for an additional three years. Topline results were available for all patients at four months (one month after last MAD dose), and six months, and were consistent with preliminary findings reported at the Foundation for Angelman Syndrome Therapeutics (FAST) meeting in November 2023. Topline data included:

• Safety assessment was the primary objective of the trial and ION582 was safe and well tolerated at all dose levels. Adverse events in the trial were consistent with patient medical histories, Angelman syndrome diagnosis or related to intrathecal administration.
• ION582 showed consistent effects across multiple objective and subjective measures used to assess functioning in individuals living with Angelman syndrome. These include the Bayley-4, an objective physician assessment of clinical functioning, Angelman Syndrome Clinical Global Improvement Change (SAS-CGI-C) scale, which evaluates clinicians' impressions, and the Vineland-3 and Observer-Reported Communication Ability (ORCA) measures, which are parent-reported assessment tools. These positive results correlated with positive changes in EEG activity including a reduction in slow wave delta activity.
• At six months, approximately 65% of patients achieved an improvement in cognition on the Bayley-4. While no direct comparisons should be made, these improvements exceeded improvements seen in natural history studies over the same time period.
• At six months, approximately 70% of patients showed improvement on Bayley-4 measures of receptive and/or expressive communication. While no direct comparisons should be made, these changes exceeded improvements seen in natural history studies over the same time period.
• At six months, approximately 65% of patients showed improvements in Bayley-4 measures of fine and gross motor skills. While no direct comparisons should be made, these changes exceeded improvements seen in natural history studies over the same time period.

Ionis expects to report detailed results from the HALOS study at the Angelman Syndrome Foundation meeting in July. ION582 has received Orphan Drug designation in the U.S. The HALOS Phase 1/2a open-label trial is evaluating safety, tolerability, pharmacokinetics and pharmacodynamics in addition to certain clinical outcomes measures.


Ionis expects to report detailed results from the HALOS study at the Angelman Syndrome Foundation meeting in July

3q in conjunction with our data!!! Months of fire await us!!!


https://ir.ionispharma.com/news-rel...sitive-topline-results-phase-12a-trial-ion582