Roche stopping testing, development of rugonersen to treat Angelman

Children in Phase 1 trial given option to move into monthslong extension study

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Following lackluster data in Phase 1 testing, Roche announced it will not initiate new trials of the experimental therapy rugonersen (RO7248824) in treating people with Angelman syndrome.

Although the therapy “has demonstrated an acceptable safety profile,” the company stated in a release, it will “not to move forward with a new clinical trial for rugonersen.” Rather, it would seek an “external partner to take over” the potential therapy’s continued development.

Angelman patients taking part in the TANGELO Phase 1 clinical trial (NCT04428281) will be given the option of continuing with rugonersen treatment in an open-label extension study that will run until February 2024.

Families of children in the trial are advised to contact their clinical team to discuss next steps.

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Rugonersen is designed to boost activity of the UBE3A gene, whose dysfunction causes Angelman. It belongs to a class of genetic medicines called antisense oligonucleotides or ASOs, and it is intended to be administered via a spinal canal (intrathecal) injection done under general anesthesia.

The TANGELO trial, which opened in August 2020, has been evaluating rugonersen in about 74 children with Angelman, ages 1 to 12. Its main goals are to determine the treatment’s safety and pharmacological properties, and results have been generally positive, according to Roche.

However, efficacy data have so far fallen short of criteria that would be needed to justify continued investment in the therapy, the company reported. Positive findings were seen on measures of the electrical activity in patients’ brains, but other assessments did not meet criteria set by Roche to keep the program going.

Roche will release trial findings “in due course,” it stated, and is now looking for other companies to take over rugonersen’s development.

“We know this is disappointing, first and most importantly for the families who have been in this trial. Before anything else, we want to acknowledge that this news is harder for you than anyone else, and we all, as a community, owe you our deepest gratitude,” the Foundation for Angelman Syndrome Therapeutics (FAST) stated in its announcement. “Your sacrifices and time spent were on behalf not just of your own loved ones but all of ours. Every study provides valuable insights and new knowledge about AS, and this one is no exception.”

Roche will continue developmental work for its other experimental Angelman therapy, alogabat, an oral treatment designed to activate certain brain receptors that are less active in Angelman patients. The company is running an open-label Phase 2 study (NCT05630066) testing alogabat in Angelman patients, ages 5 to 17, whose disease is caused by maternal deletion as confirmed by genetic analyses.

The alogabat study is actively recruiting patients at sites in Illinois and in Spain. FAST also announced that the company is working to “activate sites” for the Phase 2 trial.