PhIII bust forces Ultragenyx to scrap drug for rare muscle disease

Emil Kakkis, Ultragenyx

Analysts had been speculating that a success in Ultragenyx’s Phase III study of Ace-ER for rare cases of GNE myopathy could trigger some near-term regulatory filings. Now, they’re being forced to write it off completely as investigators report that the drug failed the primary and secondary endpoints, spurring the biotech to write it off completely.

The primary goal for the Phase III study of Aceneuramic Acid Prolonged Release, which enrolled more than 80 patients, was a composite test for upper extremity muscles. The secondaries also focused on muscle strength as well. But after reporting what it terms encouraging mid-stage data, the therapy flunked the pivotal test.

Shares of Ultragenyx slid 10% on the news.

GNEM is a severe muscle disease caused by an enzyme deficiency.

Novato, CA-based Ultragenyx $RARE had tried, and failed to win over European regulators for a conditional approval after its expert advisors concluded last year that they wanted to see the Phase III data before they approved the marketing. For some analysts like Leerink’s Joseph Schwartz, the Phase II data left a lot to be desired. He noted:

Investors may recall that the earlier 48-week Ph.2 study was designed to serve as a hypothesis-generating exploration study. This Ph.2 study had other issues including a small sample size, a lack of primary endpoint, and a pre-specified unblinding that all contributed to the investors’ lowered sentiment. Although mgmt. expressed optimism that a Ph.3 study would address the preceding trial’s weaknesses and demonstrate more robust efficacy data, we believe that progress on this asset and the prospects of GNEM was not a priority amongst investors.

Ultragenyx has a number of projects in the clinic, and will turn to the other work as it completes last rites for Ace-ER. There’s a BLA being planned for burosumab, a drug developed with Japan’s Kyowa Hakko Kirin that posted positive Phase III results in April for X-linked hypophosphatemia (XLH) and Tumor-induced osteomalacia (TIO). But the biotech has also had other recent setbacks, including a failed Phase II for UX007 , which was tested as a treatment for glucose transporter type-1 deficiency syndrome—or Glut1 DS—among a small group of patients. The drug only cut the rate of seizures in the drug arm by 13.4% compared to the placebo arm, falling short of statistical significance.

“We are disappointed by these results, as we had hoped that Ace-ER would offer a new option for GNEM patients. We would like to thank the patients, caregivers, and investigators involved in the Ace-ER development program,” said Emil Kakkis, CEO at Ultragenyx. “This outcome does not affect our overall strategy, as the company moves forward with multiple preclinical and clinical programs and regulatory filings.”

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