FDA Approves First Treatment for MCT8 Deficiency

The U.S. Food and Drug Administration has approved Egetis Therapeutics’ Emcitate, a once-daily treatment for peripheral thyrotoxicosis in people with ultra-rare genetic disorder MCT8 deficiency.

The decision makes Emcitate the first FDA approval of a therapy for the disorder, also known as Allan-Herndon-Dudley syndrome. The drug is intended to lower dangerously high thyroid hormone levels in the bloodstream and ease related cardiovascular and metabolic effects, including rapid heart rate and elevated blood pressure. It does not correct the underlying genetic defect or restore thyroid hormone delivery to the brain.

MCT8 deficiency primarily affects males and is caused by mutations in the gene that produces MCT8, a transporter protein that helps move thyroid hormone into cells, including across the blood-brain barrier. When the transporter does not work properly, the brain receives too little thyroid hormone while excess hormone remains in the blood.

The imbalance can lead to profound developmental and physical challenges. Many people with the disorder cannot sit or walk independently and have absent or severely limited speech, intellectual disability, feeding difficulties, and chronic stress on the heart and metabolism.

Emcitate’s active ingredient, tiratricol, is designed to bypass the defective MCT8 transporter. Unlike thyroid hormone, which accumulates in the bloodstream in people with the condition, tiratricol can enter cells without depending on the broken transporter, the FDA said.

“The challenge in treating MCT8 deficiency has always been that the protein needed to deliver thyroid hormone into cells is the one that isn’t working,” said Hylton Joffe, director of the Office of Cardiology, Hematology, Endocrinology, and Nephrology in the FDA’s Center for Drug Evaluation and Research. “This drug sidesteps that problem, as its active ingredient, tiratricol, can enter cells on its own without relying on the broken transporter, leading to a decrease in the elevated blood thyroid hormone levels.”

The approval was supported by two clinical studies involving patients from infancy through adulthood: an international, multicenter, randomized, placebo-controlled trial and a longer-term open-label study. Across the studies, people treated with Emcitate had lower levels of excess thyroid hormone in their blood and improvements in measures affected by those hormone levels, including systolic blood pressure and heart rate.

Emcitate is supplied as tablets that are mixed into a liquid suspension and taken once daily. It can be administered by mouth or through a feeding tube, an important option for patients with swallowing or feeding challenges.

The most common side effects reported with the therapy were diarrhea, vomiting, rash, and excessive sweating. People taking another thyroid medication should speak with their clinician before beginning Emcitate because the medicines should not be used together.

The FDA granted the therapy Orphan Drug, Rare Pediatric Disease, Fast Track, and Breakthrough Therapy designations, as well as Priority Review.