- Ultragenyx Pharmaceutical Inc. is terminating development of its neuromuscular disorder medicine following a late-stage failure that pushed down the rare disease drugmaker's stock.
- Extended release aceneuramic acid (Ace-ER) didn't significantly improve arm strength — the Phase 3 study's primary endpoint — for patients with GNE myopathy compared to placebo, according to topline results released Tuesday. The drug also didn't meet three key secondary endpoints that evaluated patients' physical functions, leg muscle strength and knee extension force.
- Ultragenyx shares traded at $51 apiece by market's open Wednesday, down more than 13% from the prior day's close. The company's stock has fallen about 27% year to date, hurt also by a Phase 2 flop of its drug UX007 in patients with glucose transporter type-1 deficiency syndrome (Glut1 DS).
In an Aug. 22 statement, Ultragenyx CEO Emil Kakkis said Ace-ER's failure, though disappointing, doesn't impair Ultragenyx's "overall strategy," which includes the continued development of a few other programs that stretch from pre-clinical to regulatory stages.
The company's pipeline, however, has stirred some concern among investors. Jefferies analyst Maury Raycroft, for example, wrote in an Aug. 22 note that the investment bank had pegged the GNE myopathy program as riskier than other Ultragenyx programs based on mixed early- and mid-stage clinical results.
Evercore ISI, another investment bank, had similar concerns.
"We had always viewed this program as speculative given complex biology that was not particularly well defined, in addition to the mixed benefit in the prior Phase 2 study," Evercore ISI analyst Steven Breazzano wrote in his own Aug. 22 note concerning the Ace-ER failure. "That said, the latest setback removes a potential source of upside from the stock and highlights a pipeline with meaningful, and underappreciated, clinical risk."
Ultragenyx's other main pipeline candidates include KRN23 (burosumab), a treatment for X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia; Vestronidase alpha, a treatment for Mucopolysaccharidosis 7 (MPS 7); and UX007 (triheptanoin), a treatment for long-chain fatty acid oxidation disorders and Glut1 DS.
KRN23 (burosumab) is arguably the Novato, California-based drugmaker's most important asset at the moment. A Biologics License Application for the X-linked hypophosphatemia (XLH) treatment should come by the end of August. And if it gains approval, KRN23 would allow Ultragenyx to shed its clinical-stage title.
UX007 and vestronidase alpha, however, look to be a bit more troublesome.
In March, the drug failed a mid-stage study testing it as a seizure medication for Glut1 DS patients. In spite of the setback, Ultragenyx has continued developing the drug, pushing forward with a Phase 3 study evaluating it as a therapy for Glut1 DS patients with motor disorders.
"Similar to Ace-ER, we view the biology here as complex and the recent miss in the Phase 2 study in glut1ds patients with the seizure phenotype highlights the clinical risk, in our view," Breazzano wrote in his Aug 22 note.
While vestronidase alpha doesn't have those same clinical maladies, investors have questioned exactly how much it can add to Ultragenyx's business and bottom lines.
"Vestronidase alpha is approaching its November PDUFA date, and while we are optimistic for approval, it only adds an incremental $40-60M opportunity," Breazzano wrote.