FDA Will Entertain Ultragenyx Application for Approval of LC-FAOD Drug

August 29, 2018

Rare Daily Staff

The U.S. Food and Drug Administration told Ultragenyx Pharmaceutical that it would consider an application for the approval of UX007, the company experimental therapy for long-chain fatty acid oxidation disorders (LC-FAOD) based on existing data.

LC-FAOD are 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. The inability to produce energy from fat can lead to severe depletion of glucose in the body, and serious liver, muscle and heart disease, which can lead to hospitalizations or early death.

LC-FAOD are included in newborn screening panels across the U.S. and in certain European countries. Patients with LC-FAOD are currently treated with the avoidance of fasting, low-fat/high carbohydrate diets, carnitine, and medium-chain triglyceride oil, a medical food product. Despite current therapy, many patients have significant metabolic events including hospitalizations and mortality due to LC-FAOD.

UX007 is a highly purified, pharmaceutical-grade, synthetic, seven-carbon fatty acid triglyceride. It is an investigational medicine intended to provide patients with medium-length, odd-chain fatty acids that can be metabolized to increase intermediate substrates in the Krebs cycle, a key energy-generating process. Unlike typical even-chain fatty acids, UX007 can be converted to new glucose through the Krebs cycle, potentially providing an important added therapeutic effect, particularly when glucose levels are too low.

In a 78-week sponsored phase 2 study, the data showed a 48.1 percent reduction in the mean annualized rate of major clinical events and a 50.6 percent reduction in the median annualized rate of major clinical events after 78 weeks of treatment with UX007 compared to an annualized rate of major clinical events in the 18 months prior to treatment with UX007.

There was also a 50.3 percent reduction in the mean annualized duration of major clinical events and a 76.7 percent reduction in the median annualized duration of major clinical events following 78 weeks of UX007 treatment. The safety profile was consistent with what has been previously observed with UX007.

UX007 had been in development as a potential treatment for glucose transporter type-1 deficiency syndrome (Glut1 DS) in patients with seizures, but last year a mid-stage trial of the drug failed to meet its primary endpoints.

The company said it expect to provide further details on the timing of a following after a meeting with the FDA ahead of its filing, which is expected to happen before year-end.

“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 Kakkis, CEO and President 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.”

August 29, 2018
Photo: Emil Kakkis, CEO and president of Ultragenyx

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