Shares of Ultragenyx Pharmaceutical fell nearly 45% on Wednesday aftermarket trading and extended losses to more than 40% in Thursday's premarket session after its neurodevelopmental disorder treatment failed a closely watched Phase III trial.

The drug, apazunersen, failed to meet both its main goal of improving cognitive skills and its secondary goal of overall patient response in participants with Angelman syndrome, a rare condition that affects the nervous system and impairs typical brain development in childhood.¹

The trial outcome is a major blow to the company and the patient community, since there are currently no approved disease-modifying treatments for the condition. It also marks Ultragenyx's second consecutive late-stage trial failure, a setback Jefferies analyst Maury Raycroft called "unambiguously negative" and likely to "further erode street confidence."¹

What were the trial results?

In the trial, apazunersen failed to show meaningful improvement on a test of young children's cognitive and nonverbal reasoning abilities, or on an overall measure of response across multiple developmental areas.² Ultragenyx says there was no difference between patients receiving the treatment and those on placebo that could support efficacy, prompting a review of the program's future and a decision on its disposition.² William Blair analyst Sami Corwin says the results also carry negative implications for the company's other study, Aurora, which is testing apazunersen in Angelman syndrome patients with other genotypes.

"We believe that even if the Aurora study meets its primary endpoint, commercialization will be challenging given the limited size of the addressable population," Corwin said.

Angelman syndrome currently has no approved disease-modifying treatment; care instead focuses on controlling seizures, improving sleep, supporting communication and development, and managing movement, feeding, and other medical complications. The condition occurs in about 1 in 15,000 live births and is usually caused by a loss of function in the UBE3A gene on the 15th chromosome, specifically the copy inherited from the mother.¹

Lisa Bollinger, chief medical officer at Polaryx, in a conversation with Pharmaceutical Executive noted the challenges around developing rare disease treatments. "There is a substantial cost to developing these drugs, and with these rare diseases, there are so many challenges,” said Bollinger.

How are analysts reacting?

Following the trial results, at least five brokerages slashed their price targets on the stock, according to a Reuters report.¹ TD Cowen analysts says the failure "removes a key growth driver," while Cantor Fitzgerald analyst Kristen Kluska warns that Ultragenyx "truly has to lower its spend substantially for investors to want to even consider building a position."¹ Ultragenyx says it will implement "significant expense reductions" to manage its high operating costs. Jefferies also notes that the trial failure "raises risk for competitors" like Ionis Pharmaceuticals and Oak Hill Bio, which are developing similar treatments. "The investment case has changed shape," Leerink Partners analyst Joseph Schwartz said, arguing that Ultragenyx is now "a commercial and expense story rather than a pipeline execution story."

What does this mean for Ultragenyx's broader pipeline?

As of Wednesday's close, Ultragenyx stock was up 15.4% year-to-date, with a market value of $2.62 billion, according to LSEG data, a gain the apazunersen failure has now sharply eroded.¹ The setback comes just weeks after a rare bright spot for the company, as last month, Ultragenyx's gene therapy, Genglycos, became the first to receive FDA approval to treat a rare metabolic disorder called Von Gierke disease.¹

Sources

1. Ultragenyx shares crater after Angelman syndrome drug fails late-stage trial Reuters September 3, 2026, https://www.reuters.com/business/healthcare-pharmaceuticals/ultragenyx-shares-crater-after-angelman-syndrome-drug-fails-late-stage-trial-2026-09-03/
2. Ultragenyx's rare disease drug fails in late-stage trial Reuters September 2, 2026, https://www.reuters.com/business/healthcare-pharmaceuticals/ultragenyxs-rare-disease-drug-fails-late-stage-trial-shares-plunge-2026-09-02/