Emcitate (tiratricol): FDA approval, pivotal trial and safety
Approved
Type
New molecular entity · Oral
FDA-approved use
To treat peripheral thyrotoxicosis in patients with MCT8 deficiencyWording from FDA's list of novel approvals.
FDA review
Priority reviewOrphan drug
Company
Rare Thyroid
Application
NDA 220963
Specialty
Endocrinology, Genetics
Boxed warning: Not for treatment of obesity or for weight loss
At a glance
Emcitate (tiratricol) is a thyroid hormone receptor agonist approved by the FDA for peripheral thyrotoxicosis in adults and children with MCT8 deficiency (Allan-Herndon-Dudley syndrome). In a randomized withdrawal study, serum total T3 rose after stopping the drug and stayed flat in those who continued it, a difference of 64.8 ng/dL (95% CI 44.7 to 84.8). It carries a boxed warning against use for obesity or weight loss, and treatment can cause signs of thyrotoxicosis.
What it is and how it works
Tiratricol is a thyroid hormone receptor agonist. Unlike T3 and T4, it can enter cells without the MCT8 transporter. In MCT8 deficiency, T3 cannot enter target tissues well, so the brain gets too little T3 while circulating T3 stays high. Tiratricol acts at THR-beta inside cells, can modulate hypothalamic-pituitary-thyroid axis signaling, and lowers circulating T3.
International, multicenter study with a run-in or titration period, a 30-day double-blind, placebo-controlled randomized withdrawal period, and a 6-week open-label follow-up.
Patients
20 male patients with MCT8 deficiency enrolled (median age 11 years, range 5 to 31). 15 reached the stable dose criterion and were randomized, 8 to placebo and 7 to continue the drug.
Compared with
Placebo (withdrawal of tiratricol).
Primary endpoint
Two primary end points: rate of change from baseline in serum total T3 during the 30-day period, and the proportion of participants meeting the rescue criterion (serum total T3 above the upper limit of normal).
Result
The T3 rate of change was 1.6 with placebo and 1.1 with tiratricol, a ratio of 1.5 (95% CI 1.0 to 2.2; P=0.034). The mean T3 change from baseline was 64.6 ng/dL with placebo and -0.2 ng/dL with tiratricol, a difference of 64.8 ng/dL (95% CI 44.7 to 84.8). The rescue criterion was met by 4 of 8 (50.0%) on placebo and 1 of 7 (14.3%) on tiratricol, a difference of 0.36 (95% CI -0.16 to 0.77). One participant who stopped early was counted as meeting the criterion.
Other results
All 8 on placebo had a T3 rise (range 31.9 to 135.4 ng/dL), larger than in those continuing tiratricol (range -15.6 to 26.0 ng/dL). Heart rate and systolic blood pressure showed a numerical trend toward improvement.
Safety in the trial
Adverse reactions in 20 patients included vomiting (10%), rash (10%) and hyperhidrosis (5%).
How does Emcitate (tiratricol) compare with the alternatives (Beta-blockers, Antithyroid drugs (such as propylthiouracil with levothyroxine), Supportive and multidisciplinary care) for peripheral thyrotoxicosis in patients with MCT8 deficiency? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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Triac Trial I (open-label, single-arm phase 2) NCT02060474
Design
Investigator-initiated, multicenter, open-label, single-arm phase 2 trial in eight European countries and one site in South Africa, with escalating dosing toward a target total T3 range and 12 months of treatment.
Patients
46 male pediatric and adult patients with MCT8 deficiency enrolled (median age 7.1 years, range 0.8 to 66.8). 45 had at least one follow-up thyroid measurement and were analyzed.
Compared with
None; each patient was compared with their own baseline.
Primary endpoint
Change in serum T3 from baseline to month 12. Co-primary end points were changes in TSH, free and total T4, and reverse T3.
Result
Serum T3 fell from 4.97 nmol/L to 1.82 nmol/L, a mean decrease of 3.15 nmol/L (95% CI 2.68 to 3.62; P<0.0001).
Other results
TSH fell by a mean of 1.89 mU/L (95% CI 1.39 to 2.39; P<0.0001). Free T4 fell by a mean of 6.1 pmol/L (95% CI 5.4 to 6.8; P<0.0001). Total T4 fell by 31.6 nmol/L (95% CI 28.0 to 35.2; P<0.0001). Reverse T3 fell by 0.08 nmol/L (95% CI 0.05 to 0.10; P<0.0001).
Safety in the trial
Seven treatment-related adverse events (transient sweating or irritability) occurred in 6 patients (13%). 26 serious adverse events judged unrelated to treatment occurred in 18 patients (39%), mostly hospital admissions for infection. One patient died of pulmonary sepsis with multi-organ failure, judged unrelated. One patient developed Graves disease. Per the label, transient rises in heart rate and systolic blood pressure occurred in 35% and 26% during titration.
The boxed warning states that thyroid hormones, including Emcitate, should not be used for obesity or weight loss because of the risk of serious or life-threatening thyrotoxicosis. Signs of thyrotoxicosis can occur, such as faster heart rate, higher blood pressure, diarrhea, sweating, irritability, insomnia and nightmares. They are most likely during treatment initiation and titration, or if the dose is raised after T3 has normalized. Tiratricol cross-reacts with T3 immunoassays and overestimates T3, and no FDA-authorized LC-MS/MS total T3 test is currently available. The most common adverse reactions were diarrhea, vomiting, rash and hyperhidrosis. The drug is not recommended for primary hypothyroidism.
What it competes with
No treatment has been established to correct both peripheral thyrotoxicosis and cerebral hypothyroidism in MCT8 deficiency. Care is mostly supportive and symptom directed.
Beta-blockersUsed to control tachycardia and other adrenergic symptoms. They do not address the underlying high T3 or brain hypothyroidism.
Antithyroid drugs (such as propylthiouracil with levothyroxine)Can lower T3 but do not reverse cerebral hypothyroidism. Use has been off label and limited by tolerability.
Supportive and multidisciplinary careNutrition support, physiotherapy, and management of spasticity and infections are the mainstay of care.
Bottom line for clinicians
Emcitate is for patients with MCT8 deficiency who have peripheral thyrotoxicosis, including children and adults. Evidence comes from very small studies, one of them a 15-patient randomized withdrawal and the other a single-arm trial, and the rescue-criterion difference between arms was not statistically clear. Plan for T3 monitoring with an assay method that is not affected by tiratricol cross-reactivity, and watch for thyrotoxic symptoms during titration.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 28, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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