Dive Brief:
- Ultragenyx Pharmaceutical on Monday said a nucleic acid therapy it is developing for Angelman syndrome helped improve function, thinking and behavior in study participants with the neurological disorder, positioning the biotechnology company to discuss with regulators a larger clinical trial of the treatment.
- However, Ultragenyx noted three of the study volunteers had mild or moderate weakness in their lower extremities that was judged by investors to be related to the gene therapy. Testing was previously halted due to prior reports of extremity weakness, but this time the company said regulators were not taking any additional steps in response.
- Shares in Ultragenyx fell by as much as 8% Monday morning on the news, likely in response to the adverse event reports. The data, which comes from a Phase 1/2 study, will be presented Tuesday at a medical meeting in Denver.
Dive Insight:
Monday’s results were the latest update from a flexible study testing multiple doses of Ultragenyx’s therapy, dubbed GTX-102.
The treatment — what’s known as an antisense oligonucleotide — is designed to reactivate expression of one allele of a gene called UBE3A that’s silenced in people with Angelman. So far, Ultragenyx has treated 74 pediatric patients in different cohorts of the trial.
The focus of Monday’s disclosure was data from 24 trial volunteers enrolled in “expansion” study cohorts and followed for about six months. Treatment led to positive changes in cognition, behavior, hyperactivity, sleep and motor function on a range of tests used to assess Angelman symptoms, Ultragenyx said. Some of these changes were “clinically significant,” or exceeded what was reported in earlier study cohorts, the company added.
“These kids have continued to make functional gains over time, which may ultimately lead to more independence,” said Erick Sell, the study’s lead investigator and director of an Angelman clinic at the Children’s Hospital of Eastern Ontario, in a statement provided by Ultragenyx.
The lower extremity weakness reported in three participants resolved without any lasting effects, according to Ultragenyx, and one has retreated without the side effect recurring. The company informed the Food and Drug Administration, as well as other regulators, but the agencies did not request it take any additional steps. (Treatment had been allowed to resume at lower doses following the prior study halt.)
“[W]hile the efficacy results are encouraging, additional signals of lower extremity weakness will likely dampen investor excitement,” wrote Joseph Schwartz, an analyst at Leerink Partners, in a Monday note to clients.
Cantor Fitzgerald analyst Kristen Kluska similarly found Ultragenyx’s data supportive of GTX-102’s effectiveness, but described the program as “high-risk, high-reward.”
The company expects to meet with the FDA by mid-year to discuss the results and has prepared designs for a Phase 3 trial.
About 60,000 people in “commercially accessible” geographies are estimated to have Angelman, according to Ultragenyx. People with the disorder experience cognitive and motor impairment as well as seizures. Most don’t speak, and some are unable to walk.
The condition, which has no approved therapies, can misdiagnosed as autism or cerebral palsy.