Ultragenyx dumps rare nervous system disorder program after phase 3 flop

An axe in a stump
The phase 3 data follow a disappointing phase 2 readout for UX007 in March last year. (Rebecca Siegel/CC BY 2.0)

Ultragenyx is abandoning its glucose transporter type-1 deficiency syndrome (Glut1 DS) program after its drug UX007 missed its endpoints in a phase 3 trial of the rare genetic disorder. This doesn’t spell the end for UX007, though, as the drug is still on track in a different group of diseases: long-chain fatty acid oxidation disorders. 

Glut1 DS is caused by mutations in the SLC2A1 gene, which codes for a protein that helps transport glucose into cells for use as fuel. This protein does not work properly in people with Glut1 DS, who experience nervous system symptoms, including recurrent seizures, developmental delay and movement abnormalities. 

The phase 3 study involved 44 children and adults with Glut1 DS experiencing disabling paroxysmal movement disorders in which they have episodes of abnormal movements. UX007 failed to significantly reduce the frequency of these episodes over placebo, missing its primary endpoint, Ultragenyx said in a statement. It also missed its key secondary endpoints. The study’s secondary endpoints included duration of disabling paroxysmal movement episodes, walking capacity and endurance, and patient-reported health-related quality of life assessments of physical function, mobility, upper extremity function, fatigue and pain. 

“We had previously observed significant improvements in individual cases of Glut1 DS with UX007 and so we are particularly disappointed by the results of the Glut1 DS study in a larger group of patients that did not demonstrate this same effect,” said Ultragenyx CEO Emil Kakkis, M.D., Ph.D., in the statement. 

RELATED: Ultragenyx under pressure as seizure drug fails phase 2 test 

Ultragenyx’s stock dipped 13% on the news Friday morning. 

The phase 3 data follow a disappointing phase 2 readout for UX007 in March last year. That study evaluated the drug in a slightly different population, people with Glut1 DS who specifically have seizures. After eight weeks of treatment, the drug cut the seizure rate by around 13% compared to placebo, but that wasn't enough to reach statistical significance. 

While it failed that endpoint, Kakkis played up the positives: that UX007 was able to reduce absence seizures, or a brief loss and recovery of consciousness, which indicated a “clinically meaningful effect.” 

Now, with the Glut1 DS program terminated, Ultragenyx is moving forward with UX007 in long-chain fatty acid disorders. The company has an upcoming discussion with the European Medicines Agency as well as a pre-NDA meeting scheduled with the FDA. It expects to provide an update later this year.