Ultragenyx’s Angelman Syndrome Trial Fails, Sending Shares Down 43%

Shares of Ultragenyx plunged 43% in after-hours trading after the company’s rare disease drug candidate failed to meet its goals in a phase 3 trial.

According to U.S. biotech and pharmaceutical news outlet Fierce Biotech on the 2nd (local time), Ultragenyx said its phase 3 trial, Aspire, evaluating the Angelman syndrome drug candidate aparuzanersen, failed to meet its primary endpoint.

Angelman syndrome is a rare genetic disorder that affects the nervous system and causes severe physical and learning disabilities.

In the trial, aparuzanersen failed to meet the primary endpoint of change from baseline in the Bayley-4 Cognitive Raw Score, a measure of cognitive function. It also missed the secondary endpoint, which measured net response on the Multi-Domain Responder Index, a measure of clinical function.

The company did not disclose specific figures or detailed results.

“Considering everything we observed in the phase 1/2 clinical program and long-term extension studies, we are disappointed by the Aspire results,” Emil Kakkis, CEO of Ultragenyx, said in a statement.

“We are even more disappointed for the global patient community that has invested so much in early research to provide the first treatment for their children,” he added.

Following the failure, Ultragenyx said it would reassess the aparuzanersen program and decide what to do with it going forward. The company also said it would “evaluate planned operations to define and implement significant cost savings.”

Ultragenyx previously cut 10% of its workforce in February. At the time, it also signaled cost cuts after two late-stage trials of treatments for osteogenesis imperfecta failed.

The phase 3 failure came just two weeks after the U.S. Food and Drug Administration granted accelerated approval to the glycogen storage disease type 1a (GSDIa) gene therapy Zynteglo.

The company is also awaiting a decision on approval of its other gene therapy, UX111, for Sanfilippo syndrome. The Prescription Drug User Fee Act (PDUFA) action date is the 19th.

William Blair analysts said they were “disappointed” by the aparuzanersen data, but noted that they had always viewed the trial as “high risk, high reward.”

They said the failure could also be a negative signal for Aurora, a separate trial evaluating aparuzanersen in patients with Angelman syndrome across genotypes and age groups. “Even if Aurora meets its primary endpoint, commercialization will be difficult because the eligible patient population is limited,” they added.

There are currently no approved disease-modifying treatments for Angelman syndrome. Ionis is furthest along, with plans to complete enrollment this summer in Reveal, a phase 3 trial of its RNA-targeted antisense therapy obudanersen.