Tiratricol (1) – Emcitate®

• Clinical trials
  • The TRIAC I study is a single-arm, open-label, multicentre Phase IIb trial designed to evaluate the safety and efficacy of tiratricol in patients with MCT8 deficiency over a 12-month period.

Individuals with monocarboxylate transporter 8 (MCT8) deficiency (Allan-Herndon-Dudley syndrome), for the treatment of peripheral thyrotoxicosis from birth

• For individuals with monocarboxylate transporter 8 (MCT8) deficiency (Allan-Herndon-Dudley syndrome), for the treatment of peripheral thyrotoxicosis from birth, there is a hint of a non-quantifiable additional benefit for tiratricol, as the scientific evidence does not permit quantification.
• The strength of the evidence is classified as ‘hint’ due to the single-arm study design.
• mortality
  • The endpoint ‘deaths’ was recorded as part of the safety assessment. One death occurred in the study. However, as no comparative data are available, no conclusions can be drawn regarding the extent of the additional benefit for the mortality category.
• Morbidity – Serum concentration of triiodothyronine (T3)
  • The concentration of the thyroid hormone T3 in serum is a clinically relevant laboratory parameter in this therapeutic indication, used for diagnosis and to guide treatment. Normalisation of serum levels is considered an important treatment goal in peripheral thyrotoxicosis.
  • However, no valid data could be identified to show what effects a specific change in T3 concentration has on the symptoms specific to each individual patient. Therefore, this endpoint is considered only as a supplementary measure.
• Morbidity – Anthropometric parameters
  • Anthropometric parameters can be regarded as patient-relevant morbidity parameters, particularly in children with characteristic, disease-related growth disorders. Data adjusted for age and sex (z-scores) are preferred over absolute values.
  • For the present benefit assessment, data on height and body weight are compared with those of the healthy reference population (WHO reference population). However, it should be noted that the present analyses also include data from adults whose physical development is already complete.
  • The TRIAC I study shows no significant change in the z-score at the end of the study compared with baseline for either body weight or height.
  • Overall, however, interpreting the significance of the available data is severe, as the non-comparative nature of the data means it is not possible to assess the findings in relation to the natural course of the disease in this patient population.
• Morbidity – Further endpoints
  • The patient-reported endpoints collected in the TRIAC I study – the Gross Motor Function Measure-88 (GMFM-88), the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III) and the Vineland Adaptive Behaviour Scales – Second Edition (VABS-II) for neurocognitive development, were not used for the benefit assessment due to the minor response rates (<70 %).
• Overall view
  • The results of the single-arm TRIAC I study on mortality, morbidity and side effects are available for this benefit assessment.
  • Due to the lack of a comparator, it is not possible to quantify the extent of the additional benefit on the basis of these data.
  • In its overall assessment, the G-BA classifies the extent of the additional benefit of Tiraticol for the treatment of peripheral thyrotoxicosis in individuals with MCT8 deficiency (Allan-Herndon-Dudley syndrome) as non-quantifiable, because the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.