Ultragenyx had been on a roll with its recent FDA approval of Genglycos, but the company has finally been hit with a bad phase 3 failure.
The late-stage Aspire trial was evaluating its investigational asset apazunersen in Angelman syndrome, a rare genetic disorder that impacts the nervous system and results in serious physical and learning disabilities.
The trial was a bust. The drug failed to achieve the primary outcome of change in Bayley-4 cognitive raw score, and was also not successful on the secondary endpoint of net response on the Multidomain Responder Index (MDRI), a measure of clinical function. The company did not provide any data or details regarding the trial.
Executive Leadership Acknowledges Disappointment
The poor results were rather honestly put down by the Ultragenyx executive team, who didn’t try to turn a bright side on this news.
“After reviewing the entirety of our Phase 1/2 clinical development program and long-term extension study, we are disappointed in the Aspire result,” said Emil Kakkis, President and CEO of Ultragenyx, in a release.
“Not only that, we are disappointed for the global patient community that has so far invested a lot of effort in the early research, hoping to get a first-ever treatment for their children.”
Stock Plummets as Company Signals Expense Reductions
The news caused Ultragenyx stock to plummet 43% in after-hours trading. The future of the drug remains in the balance, with Ultragenyx saying that it’s now looking over the apazunersen program “in light of this outcome and [will] make a decision on its disposition.”
This has also prompted the biopharma to “assess its planned operations to define and implement significant expense reductions.” Details of what these reductions will be were not provided.
As of the time of this post, Ultragenyx has yet to comment on Fierce’s request for additional details.
Ultragenyx has previously announced ‘expense reductions’ that resulted in a 10% reduction in its workforce in February. This follows on the heels of two failed late-stage brittle bone disease trials.
Regulatory Wins and Upcoming Milestones
The new phase 3 setback comes just two weeks after the FDA gave an accelerated go-ahead to pariglasgene brecaparvovec-opnr, Ultragenyx’s AAV gene therapy for the rare genetic disorder glycogen storage disease type Ia (GSDIa), under the name Genglycos.
The company is also on the verge of getting yet another approval for another gene therapy, UX111, in Sanfilippo syndrome, which is scheduled for a PDUFA date on September 19th, no more than a few weeks away.
The data from apazunersen “disappointed” analysts at William Blair, but the analysts always felt the trial was a “high risk, high reward” study.
The failure is seen as a wrong read-through by the shop for the separate study of apazunersen in patients with Angelman syndrome by genotype and age groups. “No matter how the Aurora study performs on its primary endpoint, we believe commercialization will be difficult because the size of the addressable population is limited,” they continued.
At this time, there is no cure or approved disease-modifying drugs for Angelman. Other firms are also developing drugs for the disease, though, with Ionis the most advanced, which enrolled patients in its phase 3 Reveal trial of RNA-targeted antisense asset obudanersen this summer.
Ultragenyx has suffered a significant clinical setback after its Phase 3 Aspire study of apazunersen (GTX-102) in Angelman syndrome failed to achieve its main efficacy goals. The results represent a major challenge for Ultragenyx as it evaluates the future of the program and reassesses its broader development strategy.
The Aspire study did not meet its primary endpoint, which measured change from baseline in the Bayley-4 cognitive raw score. The trial also failed to achieve its key secondary endpoint based on the Multidomain Responder Index (MDRI). Ultragenyx said there were no meaningful differences between treated and control groups that supported an efficacy benefit.
What Happened in the Ultragenyx Phase 3 Study?
Apazunersen was being developed as a potential treatment for Angelman syndrome, a rare genetic neurological disorder associated with developmental and cognitive challenges.
