- A medication for lowering the number of seizures experienced by patients with an uncommon genetic mutation has failed a Phase 2 study.
- Ultragenyx Pharmaceutical's drug UX007, or triheptanoin, did not meet its primary endpoint of reducing the frequency of seizures better than placebo in patients with glucose transporter type-1 deficiency syndrome (Glut1 DS).
- As its name suggests, the syndrome stems from a mutation that stifles the transportation of glucose into cells. The effects of that stranglehold are especially prominent in the brain, which uses glucose as a primary source of energy and therefore can lose functionality when cut off from supplies of the sugar. Since the early 1990s, only about 500 cases of the disease have been reported, according to the U.S. National Library of Medicine.
Despite the mid-stage failure, Ultragenyx isn't done with triheptanoin just yet. The rare disease drugmaker said in a March 22 statement it plans to continue an ongoing Phase 3 study evaluating the candidate as a treatment for Glut1 DS patients demonstrating motor disorders. That study enrolled 40 patients and began in January.
Having a positive readout for both studies, however, was key to Ultragenyx's plan for filing a New Drug Application. In fact, the company revealed in November 2015 it was scrapping plans for an interim analysis of the mid-stage trial as a way "to preserve the integrity of the Phase 2 study and maximize its utility from a regulatory perspective."
But over the course of the eight-week study, Glut1 DS patients taking the drug reported a statistically insignificant 13.4% reduction in seizures compared to those receiving placebo. Investigators determined the results based diary entries recorded by the patients.
While a secondary analysis of the data showed a 47.3% reduction in absence seizures — a type characterized by a short period of blankly staring off into space and fluttering eyes — among the 19 patients who reported having such seizures at baseline, that figure was not statistically significant.
"These data suggest that UX007 has a clinically meaningful effect in Glut1DS patients with absence seizures," Ultragenyx CEO Emil Kakkis said in a hopeful Wednesday statement.
Investors were less optimistic, however. Company stock was down more than 7% to $72.61 per share in Thursday morning trading.
Ultragenyx is also investigating triheptanoin as a treatment for fatty acid oxidation disorders (FAOD), a rare condition that hampers a person's ability to turn fat into energy, thereby causing low blood sugar. Back in 2015, the Food and Drug Administration granted triheptanoin an orphan drug designation for that indication.
Triheptanoin is a synthetic, medium chain fatty acid triglyceride that breaks down into smaller molecules called acetyl CoAs and propionyl CoAs when in the body. Those molecules are key components in what's known as the Krebs cycle, which converts glucose to energy. Triheptanoin, therefore, aims to be an alternative source of those energy-generating ingredients.