Drug Development, FDA

A former failure in PhII, the go-go FDA says it’s ready to consider an accelerated shortcut for Ultragenyx’s UX007

More than a year after Ultragenyx $RARE announced the failure of a Phase II study for its seizure medication UX007, the rare disease specialist says the FDA has now offered a thumbs-up for its willingness to consider an accelerated approval for a different indication.

The biotech is pursuing an OK for long-chain fatty acid oxidation disorders after piecing together data that spotlighted a drop in major clinical events for LC-FAOD.

As the company explains, LC-FAOD represents “a group of autosomal recessive genetic disorders characterized by metabolic deficiencies in which the body is unable to convert long-chain fatty acids into energy.” Without that, there’s a severe depletion of glucose that can cause havoc in a child. It’s currently treated with an ultra-low carb ketogenic diet, which is a common therapy for epilepsy and seizures, where Ultragenyx originally looked for positive data.

Analysts at JMP Securities noted a few days ago that in their conversations with Ultragenyx execs, they made it clear that regulators had already determined the biotech’s mid-stage data were “confounded and not sufficient to pursue a filing.”

Now, suddenly, that’s all changed.

This accelerates our launch timelines. Previously, we conservatively modeled a U.S. launch in 2021 which we now believe could come as early as 2020. Ultragenyx anticipates a pre-NDA meeting in 2H18 after which it will provide additional details; in the meantime, we estimate a submission in 1H2019.

Emil Kakkis, Ultragenyx

The earlier mid-stage failure was plain. UX007 is a drug designed to address glucose transporter type-1 deficiency syndrome — or Glut1 DS — in children by getting glucose into the brains of the genetically afflicted group. Without the right level of glucose, patients have a tendency to experience repeated seizures. 

In the study, the drug didn’t work. Tracking observable as well as “absence seizures,” a temporary loss of attention often marked by a distant stare, researchers recorded an unimpressive 13.4% response rate in overall seizure frequency (p=0.41) among 25 patients in the drug arm and 11 in the placebo group. That was the primary endpoint.


If you take out the more severe observable seizure rate and concentrate on a secondary endpoint for the so-called absence seizures, the drug sparked a 47% drop in their small group. And that was statistically significant.

In their statement today, the biotech says that they cobbled together a variety of data that was available, highlighting a significant drop in “the mean annualized rate of major clinical events.”

The FDA under Scott Gottlieb has repeatedly signaled their willingness to examine new approaches to shortening the timeline on drug development. And Ultragenyx says it will be ready to roll if they get a green light.

Shares of Ultragenyx, which has enjoyed a couple of key approvals, are up 3% in pre-market trading.

“We appreciate FDA’s review of multiple data submissions and collaboration with us to develop a path for an early filing, and it is our commitment to get this important potential treatment to patients with this serious disease as quickly as possible,” said Emil D. Kakkis, the CEO of Ultragenyx. “We will meet with the FDA to discuss the details of the NDA submission and, if approved, appropriate post-approval commitments to further evaluate long-term outcomes of UX007 in patients with LC-FAOD.” 

Image: YouTube

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