European Medicines Agency (EMA) has recommended granting a marketing authorization in the European Union (EU) for Emcitate (tiratricol), an oral medication for individuals with peripheral thyrotoxicosis (unreasonably elevated levels of circulating thyroid hormones) in patients with monocarboxylate transporter 8 (MCT8) deficiency.
Allan-Herndon-Dudley syndrome (AHDS) or MCT8 deficiency is an ultra-rare, chronic and severely debilitating disease caused by mutations in the gene coding for the thyroid hormone transporter MCT8 protein. This prevents the thyroid hormones from entering cells in the brain and delays brain development in individuals with AHDS. This lack of thyroid hormone in the brain leads to severe intellectual and motor disability. Patients only rarely achieve independent sitting, and most will not be able to maintain head control. At the same time, there is a build-up of thyroid hormones in other parts of the body, which can cause peripheral thyrotoxicosis manifesting itself in symptoms of low body weight, tachycardia, and muscle wasting. This may result in serious complications like heart failure and death. Given that the mutation is in the X-chromosome, the condition occurs almost exclusively in males.
There is an unmet medical need for treatments of AHDS as there are no medicines currently authorised in the EU to treat this disease. The active substance of Emcitate is tiratricol, an analogue of the thyroid hormone T3, the most important active thyroid hormone. Tiratricol binds with high affinity to thyroid receptors and does not require MCT8 to enter cells. It exerts similar biologic effects to T3 and can restore normal thyroid hormone activity in MCT8-dependent tissues.
This recommendation for Emcitate as a treatment for peripheral thyrotoxicosis is based on the results of a pivotal single-arm, open-label study conducted in children and adults treated with an individually adjusted dose of tiratricol for up to 12 months. Tiratricol reduced the mean serum T3 concentration by more than 63% at month 12. All patients improved in at least one of the study endpoints: body weight, resting heart rate, or systolic blood pressure. The average number of premature atrial contractions (extra heartbeats) also decreased. Emcitate did not improve neurodevelopmental delay. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, considering the potential role or use of this medicine in the context of the national health system of that country.
The most frequent side effects in patients treated with Emcitate were excessive sweating, irritability, anxiety and nightmares. These reactions usually occurred at the start of treatment and / or when the dose was increased, and generally resolved during treatment.
