FDA approves tiratricol as first treatment for peripheral thyrotoxicosis in MCT8 deficiency

Patients with monocarboxylate transporter 8 (MCT8) deficiency now have an FDA-approved option to address the chronic peripheral thyrotoxicosis that accompanies the disorder's severe neurodevelopmental impairment.

On September 28, 2026, the FDA approved tiratricol (Emcitate; Egetis Therapeutics) tablets for oral suspension to treat peripheral thyrotoxicosis in patients with MCT8 deficiency, also known as Allan-Herndon-Dudley syndrome.¹ Tiratricol is the first FDA-approved therapy for the condition.¹

"Until now, patients living with MCT8 deficiency and their families had no FDA-approved treatment option," said Marina Zemskova, MD, deputy director of the Division of General Endocrinology in the FDA's Center for Drug Evaluation and Research.¹

MCT8 deficiency pathophysiology and the rationale for tiratricol

MCT8 deficiency is caused by pathogenic variants in the gene encoding the MCT8 transporter, which carries thyroid hormone across the blood-brain barrier.¹ Without a functional transporter, the brain receives too little thyroid hormone while triiodothyronine (T3) accumulates in the circulation.¹ The result is a dual phenotype: profound intellectual and motor disability alongside peripheral thyrotoxicosis marked by tachycardia, elevated blood pressure, and adverse metabolic effects.¹ The disorder primarily affects males, and many patients cannot sit or walk independently, have absent or severely limited speech, and have feeding difficulties.¹

Tiratricol is a T3 analogue that enters cells without relying on MCT8.¹ "This drug sidesteps that problem, as its active ingredient, tiratricol, can enter cells on its own without relying on the broken transporter," said Hylton V. Joffe, MD, MMSc, director of the Office of Cardiology, Hematology, Endocrinology, and Nephrology at the FDA.¹

ReTRIACt trial design and tiratricol efficacy in MCT8 deficiency

The FDA evaluated efficacy in 2 studies enrolling patients from infancy to adulthood: the international, randomized, placebo-controlled ReTRIACt trial (NCT05579327) and a longer-term open-label study.¹ Across both, tiratricol reduced circulating thyroid hormone levels and improved thyroid-driven cardiovascular and metabolic measures, including systolic blood pressure and heart rate.¹

ReTRIACt was a double-blind, randomized withdrawal study in which males aged 4 years and older on stable tiratricol were assigned to continue treatment or switch to placebo for 30 days or until serum total T3 exceeded the upper limit of normal.² All 8 patients randomized to placebo had increases in serum T3 (range, 0.49–2.08 nmol/L) that exceeded those in all 7 patients who continued tiratricol (range, −0.24 to 0.40 nmol/L), a statistically significant difference in the rate of T3 change (P = .034).²

Earlier data came from Triac Trial I, a single-arm, open-label phase 2 study. Serum T3 fell from a mean of 4.97 nmol/L at baseline to 1.82 nmol/L at 12 months (mean decrease, 3.15 nmol/L; 95% CI, 2.68–3.62; P < .001), and resting heart rate on electrocardiography declined by 9 beats/min.³

Tiratricol is given once daily as a liquid suspension, orally or via feeding tube.¹ The most common adverse effects were diarrhea, vomiting, rash, and excessive sweating.¹ It should not be used with other thyroid medications.¹ The application received Orphan Drug, Rare Pediatric Disease, Fast Track, and Breakthrough Therapy designations, as well as Priority Review.¹

Limitations of tiratricol data and neurodevelopmental outcomes in MCT8 deficiency

The approved indication targets peripheral thyrotoxicosis, not the neurologic manifestations that drive most of the disease burden. In Triac Trial II, which enrolled young boys, numerical gains in gross motor function on the GMFM-88 and BSID-III scales did not reach statistical significance vs historical controls, although T3 reductions were durable in all patients.⁴ Whether earlier initiation can alter neurodevelopmental trajectories remains unanswered.

The pivotal randomized evidence is also limited in size and duration, relying on a biochemical end point over 30 days in 15 patients.² The FDA announcement did not specify labeled age ranges or dosing, so clinicians should consult the full prescribing information before initiating therapy.

References

1. US Food and Drug Administration. FDA approves first treatment for MCT8 deficiency. News release. September 28, 2026. Accessed September 29, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-mct8-deficiency

2. Egetis Therapeutics. Egetis announces positive results from the ReTRIACt study of Emcitate (tiratricol) in MCT8 deficiency. News release. November 14, 2025. Accessed September 29, 2026. https://www.egetis.com/mfn_news/egetis-announces-positive-results-from-the-retriact-study-of-emcitate-tiratricol-in-mct8-deficiency/

3. Groeneweg S, Peeters RP, Moran C, et al. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019;7(9):695-706. doi:10.1016/S2213-8587(19)30155-X

4. Egetis Therapeutics. Egetis announces topline results of the phase 2 Triac Trial II with Emcitate (tiratricol) for MCT8 deficiency. News release. 2024. Accessed September 29, 2026. https://www.egetis.com/mfn_news/egetis-announces-topline-results-of-the-phase-2-triac-trial-ii-with-emcitate-tiratricol-for-mct8-deficiency/