Clinical Trials

Date: 2015-08-22

Type of information: Results

phase: 3

Announcement: results

Company: Ultragenyx Pharmaceutical (USA - CA)

Product: aceneuramic acid extended release (Ace-ER), previously known as sialic acid-extended release (SA-ER; UX001)

Action mechanism:

• monosaccharide. Aceneuramic acid (Ace-ER), previously known as sialic acid, is the United States Adopted Name (USAN) and International Nonproprietary Name (INN) for sialic acid, which is being developed for the treatment of GNE Myopathy.
• Ace-ER is designed to replace the deficient sialic acid substrate in patients with GNE myopathy.

Disease: GNE myopathy, also known as hereditary inclusion body myopathy (HIBM)

Therapeutic area: Rare diseases - Genetic diseases - Neuromuscular diseases

Country: Canada, UK, USA

Trial details:

• UX001-CL301 is a randomized, double-blind, placebo-controlled study to assess the safety and efficacy of 6 g/day sialic acid - extended release (SA-ER) treatment as compared with placebo in subjects with GNE Myopathy. The Phase 3 global, randomized, double-blind, placebo-controlled clinical study is designed to assess the efficacy and safety of six grams per day of Ace-ER over 48 weeks in 89 patients. The primary endpoint of the study is a comparison between active and placebo treated patients for the change from baseline to 48 weeks in the composite of upper extremity muscle strength as measured by hand-held dynamometry (HHD). Key secondary endpoints include the GNE myopathy-functional activity scale (GNEM-FAS), a disease-specific patient-reported outcome (PRO) that includes measures of mobility and upper-extremity function, a composite of lower extremity muscle strength, and other measures of lower-extremity muscle strength and function. The Phase 3 study design and primary endpoint were based on feedback from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). (NCT02377921).

Latest news:

• • On August 22, 2017, Ultragenyx Pharmaceutical announced that a Phase 3 study evaluating aceneuramic acid extended release (Ace-ER) in patients with GNE myopathy 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.
• 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, physical functioning using the Mobility domain of the GNE Myopathy-functional activity scale, 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.
• Ultragenyx 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.
• • On July 27, 2016, Ultragenyx Pharmaceutical  announced that it has completed patient enrollment in the Phase 3 study of aceneuramic acid extended release (Ace-ER) for the treatment of GNE myopathy. Data from the study are expected in 2017. Ultragenyx is also currently seeking conditional marketing authorization from the EMA for Ace-ER for the treatment of adults with GNE myopathy, based on data from the Phase 2 randomized, double-blind, placebo-controlled study. The Committee for Medicinal Products for Human Use (CHMP) opinion is expected in the second half of 2016, with a final decision expected in the first half of 2017. If conditional approval is granted, the Phase 3 study is expected to be required for confirmatory purposes. If conditional approval is not granted, the Phase 3 study would be required for approval.
• • On May 28, 2015, Ultragenyx Pharmaceutical, a biopharmaceutical company focused on the development of novel products for rare and ultra-rare diseases, announced the initiation of the Phase 3 study of aceneuramic acid extended release (Ace-ER), previously known as sialic acid-extended release (SA-ER; UX001), tablets for the treatment of GNE Myopathy.  A Phase 2 randomized, double-blind, placebo-controlled study with Ace-ER has been completed. The data showed a statistically significant difference in the upper extremity composite of muscle strength at 48 weeks with a higher-dose group compared to a lower-dose group. Ace-ER appeared to be generally safe and well tolerated with no serious adverse events observed to date. Over an approximate two-year treatment period in the Phase 2 study and long-term extension, Ace-ER appeared to stabilize or slow the progression of upper extremity disease when compared to the 24-week placebo group extrapolated out to two years.
• The Phase 3 global, randomized, double-blind, placebo-controlled clinical study in approximately 80 patients will assess the efficacy and safety of six grams per day of Ace-ER over 48 weeks. The primary endpoint of the study is a composite of upper extremity muscle strength as measured by hand-held dynamometry (HHD). Key secondary endpoints include the GNE Myopathy-functional activity scale (GNEM-FAS), a disease-specific patient-reported outcome (PRO) that measures mobility and upper-extremity function, and other measures of lower-extremity muscle strength. A Phase 2 randomized, double-blind, placebo-controlled study evaluating the same endpoints was completed in December 2013. The Phase 3 study design was accepted by the FDA and the EM). Data from the Phase 3 study are expected in the second half of 2016. In parallel with the conduct of the Phase 3 study, Ultragenyx intends to file a Marketing Authorization Application (MAA) with the EMA in the second half of 2015. The company seeks to obtain conditional approval from the EMA for Ace-ER for the stabilization or slowing of decline in upper extremity muscle strength in patients with GNE Myopathy based on the Phase 2 data and Scientific Advice received from the EMA. Once filed, a decision from the EMA is anticipated by the end of 2016.

Is general: Yes