The success of apazunersen in a Phase 3 trial for Angelman syndrome was a key driver of Ultragenyx’s value, according to William Blair, and the asset’s failure robs the biotech of any meaningful near-term milestones.
Ultragenyx’s investigational Angelman syndrome therapy apazunersen failed to improve cognition in a Phase 3 clinical trial, missing the trial’s key endpoints and sending the California company’s stock crashing more than 43% in after-hours trading.
The failure has forced Ultragenyx to “assess its planned operations,” according to a news release on Wednesday afternoon. The biotech intends to now focus on its “growing commercial business.” Ultragenyx has a handful of approved therapies, including the gene therapy Genglycos, approved last month for glycogen storage disease type Ia.
Ultragenyx will roll out “significant expense reductions,” though it’s unclear what this could entail specifically. BioSpace has reached out to Ultragenyx for more detail, including whether layoffs are planned.
In Aspire, Ultragenyx tested apazunersen, an antisense oligonucleotide, against a sham control in nearly 130 patients with Angelman syndrome, a rare genetic disorder that affects the nervous system and causes severe developmental delays. The study’s primary outcome was cognition, while improvement across several domains of clinical function was set as a key secondary endpoint.
Without presenting specific data, Ultragenyx on Wednesday said that apazunersen showed no significant benefit on those two measures. Looking at individual domains of clinical improvement likewise yielded no evidence that could support the asset’s efficacy.
Shares of Ultragenyx tumbled 46% to around $14 apeice on Thursday morning, as compared to $26.53 at close the day prior.
The Angelman study, dubbed Aspire, was a “high-risk/high-reward” play for Ultragenyx, William Blair told investors in a note on Wednesday. And while the firm conceded that the biotech is still looking at a potential approval later this month—for the once-rejected gene therapy San Filippo syndrome, with a decision date of Sept. 19—that verdict is likely to be an “incremental catalyst” at best.
“Our investment thesis was centered on the Angelman syndrome outcome and resulting future revenue stream,” the analysts said. With Aspire’s failure, “we do not see any key value inflection points for the company in the next 12 months,” they added.
Jefferies, meanwhile, focused on the silver lining for Ultragenyx. While the company suffered another Phase 3 flop in January—which alongside the latest failure could “erode street confidence” in the biotech—Ultragenyx “could now be more capital efficient going forward,” the analysts wrote to investors on Wednesday night.
Ultragenyx’s commercial franchise and potential remain intact with its gene therapy launches, the firm added.
Ultragenyx is also running the Aurora study for apazunersen. The Phase 2 trial is a basket study involving patients with Angelman syndrome across all genotypes and age groups. Aurora is currently enrolling, with topline data slated for 2030. William Blair has tempered its expectations of Aurora, however, noting on Wednesday that the Aspire fail is likely to have “negative implications” for the mid-stage trial.
