In a victory for the rare disease community, Oak Hill Bio has acquired global rights for rugonersen (RO7248824) from Roche and plans to initiate a Phase III study in early 2026. Roche had abandoned the drug, though not for safety reasons, but because it did not meet their internal, preset goal for efficacy.
Rugonersen is an antisense oligonucleotide (ASO) for Angelman syndrome, a rare, genetic, neurodevelopmental condition for which there is no approved disease-modifying treatment. The drug acts by unsilencing UBE3A production.
“This is a powerful signal to our community who have fought tirelessly for progress. Knowing that this work will continue means everything,” said Amanda Moore, CEO, Angelman Syndrome Foundation (ASF) and Ryan Fischer, COO, Foundation for Angelman Syndrome Therapeutics (FAST).
“We are excited to take on this program. We are incredibly impressed by the rigorous research Roche has conducted, and the promising clinical data generated to date,” said Josh Distler, CEO of Oak Hill.
He added, “We have also been moved by the dedication of the patients, families, and investigators in the Angelman community and look forward to working closely with them to fully evaluate rugonersen’s potential to improve the lives of individuals with Angelman syndrome and their families.”
“I am very glad that the development of rugonersen will continue,” said Elizabeth Berry-Kravis, MD, PhD, pediatric neurologist and principal investigator of the TANGELO trial at Rush University Medical Center. TANGELO was Roche’s Phase I trial of RO7248828.
She added, “Many of our trial participants have had meaningful improvements while in the rugonersen trial, and the TANGELO results suggest developmental and functional gains in multiple domains relative to natural history. We are very excited that the potential benefits of rugonersen will continue to be evaluated for these and other patients with Angelman syndrome.”
Angelman syndrome affects an estimated 500,000 individuals worldwide. Symptoms typically arise during early childhood and include cognitive and developmental issues, such as speech and communication difficulties, motor impairment, balance issues, and debilitating seizures. The condition is caused by a loss of function of the maternally inherited UBE3A gene.
“We are incredibly excited and deeply grateful to see Oak Hill stepping in to continue the rugonersen program for Angelman syndrome. We, along with caregivers and providers, have seen the promise of rugonersen to help those with Angelman syndrome,” said Moore.
Rugonersen was designed to modify disease progression by boosting expression of the paternal version of the UBE3A gene. In the TANGELO study, an open-label, non-randomized, adaptive study led by Roche, rugonersen demonstrated encouraging exploratory effects compared to natural history on multiple clinical measures and on a pharmacodynamic biomarker of brain function, EEG delta power.
These data were presented at FAST’s Annual Global Science Summit in November 2024. Oak Hill believes these results support rugonersen’s potential to address multiple disease domains. Oak Hill anticipates initiating a pivotal Phase III trial in early 2026 for rugonersen as a potential treatment for individuals with Angelman syndrome.
