The European Medicines Agency (EMA) has given its nod for marketing authorisation within the European Union (EU) for Emcitate (tiratricol), designed as an oral therapy targeting peripheral thyrotoxicosis, characterized by abnormal elevations of circulating thyroid hormones within individuals suffering from monocarboxylate transporter 8 (MCT8) deficiency.
This application for Emcitate was submitted by Rare Thyroid Therapeutics International AB.
Known as Allan-Herndon-Dudley syndrome (AHDS), MCT8 deficiency is a highly uncommon, chronic, and profoundly debilitating disorder stemming from mutations in the gene responsible for coding the thyroid hormone transporter, MCT8 protein. This mutation blocks the entry of thyroid hormones into brain cells, inhibiting brain development in AHDS patients. Consequently, this hormonal deficiency results in significant intellectual and motor challenges. Achieving independent sitting is rare for affected individuals, and most cannot sustain head control.
Concurrently, thyroid hormones accumulate in other bodily regions, potentially inciting peripheral thyrotoxicosis and accompanying symptoms such as low body weight, rapid heart rate, and muscle deterioration. This conundrum heightens the risk of serious health issues, including heart failure or even death.
Because the mutation affects the X-chromosome, this condition predominantly afflicts males.
An acute need for AHDS treatments persists due to the absence of authorized medications within the EU specific to this condition.
Emcitate’s active ingredient is tiratricol, a synthetic version of thyroid hormone T3, the most crucial active thyroid hormone. Tiratricol binds robustly to thyroid receptors and is capable of entering cells independently of MCT8. It mirrors T3’s biological effects and can re-establish normal thyroid hormone functions within MCT8-reliant tissues.
EMA’s endorsement for Emcitate as a remedy for peripheral thyrotoxicosis derives from a pivotal single-group, open-label research involving children and adults administered tailored tiratricol dosages over a 12-month span. Patients experienced a more than 63% decrease in average serum T3 concentrations by the twelfth month. Every participant showed improvement in at least one study metric, including body weight, heart rate at rest, or systolic blood pressure. Additionally, the regularity of premature atrial contractions, or additional heartbeats, diminished. However, Emcitate did not advance neurodevelopmental delays.
Common side effects for those treated with Emcitate included excessive sweating, irritability, anxiety, and nightmares, typically manifesting at the treatment’s commencement or upon dosage escalation, though often resolved during continued treatment.
CHMP’s positive opinion marks an intermediary phase in Emcitate’s journey towards patient availability. This recommendation will now proceed to the European Commission to decide on EU-wide marketing approval. Post-approval, individual Member States will determine pricing and reimbursement options, considering the drug’s potential implications or utility within their national healthcare systems.
On 8 November 2017, Emcitate received the designation of orphan medicinal product for treating Allan-Herndon-Dudley syndrome. Following CHMP’s favorable verdict, the Committee for Orphan Medicinal Products (COMP) will evaluate whether the orphan designation remains applicable.
Emcitate represents a hybrid medicine of Téatrois, available in France since 1974 for inhibiting thyroid stimulating hormone (TSH) secretion, particularly for patients suffering from thyroid hormone resistance syndromes and distinct thyroid cancers. Hybrid medicines partially rely on reference product data from prior pre-clinical trials and clinical tests, supplemented by new data.