Ultragenyx Announces Top-Line Results from Phase III Ace-ER GNE Myopathy Study

Ultragenyx Pharmaceutical, a biopharmaceutical company focused on the development of novel products for rare and ultra-rare diseases, announced that a Phase 3 study evaluating aceneuramic acid extended release (Ace-ER) in patients with GNE Myopathy (GNEM) did not achieve its primary endpoint of demonstrating a statistically significant difference in the upper extremity muscle strength composite score compared to placebo. The study also did not meet its key secondary endpoints. Adverse events were generally balanced between Ace-ER and placebo and safety was consistent with previously released Ace-ER data. Ultragenyx plans to discontinue further clinical development of Ace-ER.

“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 D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. “This outcome does not affect our overall strategy, as the company moves forward with multiple preclinical and clinical programs and regulatory filings.”

The Phase 3 Ace-ER study enrolled 89 adults with GNEM able to walk > 200 meters in the six minute walk test. Patients were randomized 1:1 to Ace-ER at a dose of 6g/day or placebo for 48 weeks. The study did not meet the primary endpoint of demonstrating a statistically significant improvement in UEC score (+0.74 kg, p=0.5387) for Ace-ER treated patients (n=45, -2.25 kg) compared to placebo (n=43, -2.99 kg) patients for the change from baseline to 48 weeks. There were three pre-specified key secondary endpoints, including the lower extremity muscle strength composite score as measured by hand-held dynamometry (HHD), physical functioning using the Mobility domain of the GNE Myopathy-functional activity scale (GNEM-FAS), and a measure of muscle strength in knee extensors. The study did not meet any of these key secondary endpoints.

Overall, Ace-ER was well tolerated, with slightly more patients experiencing treatment emergent adverse events and related treatment emergent adverse events. There were three serious adverse events including two on Ace-ER and one on placebo, none of which were considered treatment related. There were no discontinuations due to treatment emergent adverse events, and there have been no deaths in the study.

The company plans to terminate the development program based on these results and will work with investigators and patient groups to make available the valuable natural history data and development tools for the development of other therapies. The company will be working with investigators and patients on a reasonable transition plan for patients still on Ace-ER.