Ultragenyx Angelman therapy fails Phase 3, triggering 43% stock plunge

Key points

• Apazunersen missed both primary and secondary endpoints in the Aspire trial for Angelman syndrome.
• Ultragenyx shares fell 43% after hours following the announcement of the failed trial.
• The company is assessing the drug’s disposition and planning significant expense reductions.
• Analysts at Evercore ISI, JPMorgan, and Baird downgraded Ultragenyx, citing the loss of a key profitability driver.
• Ionis Pharma is currently the furthest along in developing a treatment for Angelman syndrome.

Background

Ultragenyx had recently received FDA approval for Genglycos, a gene therapy for glycogen storage disease type Ia, and was awaiting approval for another gene therapy for Sanfilipo syndrome. The company had previously cut 10% of its workforce after failed brittle bone disease trials. Angelman syndrome is a rare genetic condition with no current cures or approved disease-modifying treatments.

How outlets are covering it

STAT reported that the drug showed no benefit compared to a sham treatment in a large Phase 3 trial, emphasizing the blow to Ultragenyx’s business and the hopes of families. Fierce Biotech noted that the drug missed its primary endpoint of change from baseline in Bayley-4 cognitive raw score and its secondary endpoint, and that the company’s executive team was 'refreshingly honest' about the failure. Marketscreener highlighted that multiple analysts, including Evercore ISI, JPMorgan, and Baird, downgraded Ultragenyx, with Evercore ISI cutting its price target from $34 to $16. Yahoo Finance reported that Ultragenyx shares slumped 46% after hours, though this figure may include broader market movements or different trading windows compared to the 43% drop reported by Fierce Biotech.

Why it matters

The failure of apazunersen removes a key driver for Ultragenyx’s path to profitability, as its approved medicines are for mostly ultra-rare diseases. The setback also impacts the broader rare disease sector, as there are currently no cures or approved disease-modifying treatments for Angelman syndrome. The company’s planned expense reductions and the potential discontinuation of the apazunersen program could have significant implications for its financial health and future pipeline.

What to watch

Ultragenyx will decide on the disposition of the apazunersen program and implement significant expense reductions. The company is also awaiting the potential approval of UX111 for Sanfilipo syndrome, with a PDUFA date on September 19. Ionis Pharma is expected to continue its Phase 3 Reveal trial for obudanersen in Angelman syndrome.