Ultragenyx had been flying high after its recent FDA approval for Genglycos—but the company has been brought back down to earth with a damaging phase 3 flop.
The late-stage Aspire trial was assessing its investigational asset apazunersen in Angelman syndrome, a rare genetic condition that affects the nervous system and causes severe physical and learning disabilities.
The trial was a bust. The drug missed its primary endpoint of change from baseline in Bayley-4 cognitive raw score, while also falling short in its secondary endpoint, which was net response on the Multidomain Responder Index, a measure of clinical function.
The company did not give specific figures or a breakdown of the trial.
The Ultragenyx executive team's statement on the failure was refreshingly honest, with no attempt to shine a positive light on the poor results.
“Based on everything we observed in the robust Phase 1/2 clinical development program and long-term extension study, we are disappointed by the Aspire result,” said Emil Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx, in a release.
“Even more, we are disappointed for the global patient community who has invested so much in early-stage research, working to bring a first-ever treatment to their children.”
The flop sent Ultragenyx shares down 43% after hours Wednesday evening on the news. 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.” No further details on what these reductions will look like were shared.
At the time of publication, Ultragenyx had not responded to Fierce’s request for more information.
Ultragenyx has before warned of “expense reductions”, which eventually led to 10% of its workforce being cut back in February. This came after a pair of failed late-stage brittle bone disease trials.
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 poised for the potential approval of another gene therapy, UX111, in Sanfilipo syndrome, with a PDUFA date just weeks away on September 19.
Analysts at William Blair were “disappointed” by the apazunersen data but said they had always viewed the trial as “high risk, high reward.”
The shop said it sees this failure as a negative read-through for the separate Aurora study, which is assessing apazunersen in patients with Angelman syndrome across genotypes and age groups. “We believe that even if the Aurora study meets its primary endpoint, commercialization will be challenging given the limited size of the addressable population,” they added.
There are currently no cures or approved disease-modifying treatments for Angelman. There are other companies working on the condition, however, with Ionis one of the furthest along, having this summer completed enrolment in its phase 3 Reveal trial for RNA-targeted antisense asset obudanersen.