Ultragenyx Plunges With Phase III Failure, Company to Discontinue Glut1 DS Development Program


By Alex Keown


Shares of California-based Ultragenyx are down more than 15 percent this morning after the company announced its Phase III drug candidate UX007 failed to hit the mark as a treatment for patients with glucose transporter type-1 deficiency syndrome (Glut1 DS) who are experiencing disabling paroxysmal movement disorders.

This morning Ultragenyx said UX007 did not meet its primary endpoint of demonstrating a statistically significant reduction in the frequency of paroxysmal movement events compared to placebo. Additionally, the drug also failed to demonstrate a meaningful difference between treatment groups. The late-stage study also did not meet its key secondary endpoints, Ultragenyx said. The primary endpoint of the Phase III trial was the difference in frequency of disabling paroxysmal movement disorders with UX007 compared to placebo. Secondary efficacy endpoints included: duration of disabling paroxysmal movement disorder events; walking capacity and endurance; patient-reported health-related quality of life assessments of physical function, mobility, upper extremity function, fatigue and pain.

UX007 is a highly purified, synthetic seven carbon fatty acid triglyceride. It is designed to provide patients with medium-length, odd-chain fatty acids that can bypass the genetic block in long-chain fatty acid metabolism, according to company data.

Emil Kakkis, chief executive officer of Ultragenyx, said the company was disappointed with the overall Phase III outcome, particularly as researchers had observed significant improvements in individual cases of Glut1 DS with UX007.

As a result of the Phase III failures, Ultragenyx said it plans to discontinue the Glut1 DS development program and will work with investigators and patients on a reasonable transition plan for patients with Glut1 DS who are still on UX007. The company does have a separate program evaluating UX007 in long-chain fatty oxidation disorders which remains on track. Ultragenyx said the U.S. Food and Drug Administration (FDA) has accepted the Company’s proposal to submit a New Drug Application (NDA) for UX007 for the treatment of LC-FAOD based on existing data. A pre-NDA meeting is set to take place before the end of the year, the company added. Ultragenyx will discuss the data with the European Medicines Agency and expects to have an update this year.

“We continue to move forward with our UX007 program in long-chain fatty acid disorders which is not affected by this Glut1 DS outcome. We look forward to providing an update on UX007 regulatory discussions later this year,” Kakkis said in a statement.

The Phase III 3 UX007 Glut1 DS study included 44 children and adults who experienced disabling paroxysmal movement disorders associated with Glut1 DS. Patients who were randomized to receive UX007 underwent a 14-day titration period followed by an eight-week treatment period on UX007. That was followed by a two-week “washout period” that was then followed by another titration period and treatment period. Patients in the second group followed the same schedule but started with placebo and then crossed over to UX007, Ultragenyx said.

As of 10:09 a.m., shares of Ultragenyx are trading at $50.20, down from Thursday’s closing price of $59.36.



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