- The numerical improvements versus baseline observed on the primary endpoints of neurocognitive development assessed by the GMFM-88 and BSID-III scales did not show a statistically significant improvement versus historical controls.
- The trial confirmed the significant and durable reduction of endogenous T3 concentrations in all patients and the well-tolerated safety profile of tiratricol seen in previous clinical studies, despite higher dosing per kg body weight compared to previous trials.
- The trial is complementary to the data already submitted and validated in the Marketing Authorisation Application for Emcitate® (tiratricol) for treatment of MCT8 deficiency, based on the benefit of normalization of thyrotoxicosis which has been demonstrated in patients of all ages, as agreed with the
European Medicines Agency (EMA). Results from Triac Trial II will be included in the response to EMA 120-day list of questions inAugust 2024 . - The forthcoming New Drug Application in the
USA , will also be based on the already observed treatment effects on T3 concentrations and the manifestations of chronic thyrotoxicosis together with results from the ongoing ReTRIACt trial, as acknowledged by theUS Food and Drug Administration (FDA). - The Company does not consider the approvability of the product to be affected by the Triac Trial II results and the regulatory timelines remain unchanged.
- Conference call for analysts and investors to be held tomorrow
Thursday June 20 at8:00am (CEST) .
The trial confirmed the well-tolerated safety profile seen in previous clinical studies, despite higher dosing per kg body weight compared to previous studies.
Professor
We are grateful for the patients, their families, and the investigators who have participated in Triac Trial II.”
The data will be presented at a forthcoming medical meeting, submitted to a peer-reviewed medical journal and shared with regulatory authorities.
As agreed with the EMA, regulatory approval for Emcitate® (tiratricol) is based on treatment effects on T3 concentration and the manifestations of chronic thyrotoxicosis in MCT8 deficiency, demonstrated in previous clinical studies. This was reflected in the validated marketing authorisation application in the EU, submitted in
The forthcoming New Drug Application in the
The timeline for regulatory review and approval in EU remain unchanged. For the US, as previously communicated, the Company will update the market with regards to timelines for NDA submission as soon as 16 evaluable patients have concluded the ongoing ReTRIACt trial.
Webcast and teleconference on
If you wish to participate via webcast please use the link below. Via the webcast you are able to ask written questions.
https://ir.financialhearings.com/egetis-press-conference-june-2024/register
If you wish to participate via teleconference please register on the link below. After registration you will be provided phone numbers and a conference ID to access the conference. You can ask questions verbally via the teleconference. https://conference.financialhearings.com/teleconference/?id=5007609
About Triac Trial II
Trial II is conducted in patients with MCT8 deficiency, also called Allan-Herndon-Dudley Syndrome (AHDS), which is due to mutations in monocarboxylate transporter 8 (MCT8). MCT8 is a thyroid hormone transporter which is crucial for the transport of thyroid hormone from the blood into different tissues. Defective MCT8 results in a lack of thyroid hormone (hypothyroidism) in tissues that are dependent on MCT8 for thyroid hormone uptake, such as the brain. Hypothyroidism in the brain results in severe intellectual and motor disability. Another important feature of this disease is the high serum T3 concentrations in the blood. This results in thyrotoxicosis in tissues that are not dependent on MCT8 for their thyroid hormone supply. As a result, patients with MCT8 deficiency have clinical features of thyrotoxicosis such as low body weight, elevated heart rate and reduced muscle mass.
Preclinical studies have shown that the T3 analogue tiratricol is transported into cells in an MCT8-independent manner. In animal models mimicking MCT8 deficiency, tiratricol has been shown to normalize brain development if administrated during early postnatal life.
Triac Trial I (NCT02060474) has shown that tiratricol treatment in patients with MCT8 deficiency improves key clinical and biochemical features caused by the toxic effects of the high T3 concentrations. No drug related serious adverse events occurred during Triac Trial I.
Triac Trial II investigated the effect of treatment with tiratricol in young boys (≤30 months) with MCT8 deficiency. The hypothesis tested is that treatment with tiratricol will have a beneficial effect on the hypothyroid state in the brain as well as the hyperthyroid state in peripheral organs and tissues in these patients. Patients were initially treated for 96 weeks with tiratricol, and the treatment effect was evaluated after 96 weeks. After the 96-week treatment period, patients could enter Part II of the trial, evaluating long-term treatment. Patients will be followed for an additional 2 years, and treatment effect will be evaluated after 3 years and 4 years respectively from start of treatment.
For further information about Triac Trial II, please see https://clinicaltrials.gov/study/NCT02396459
About MCT8 deficiency
MCT8 deficiency, also called Allan-Herndon-Dudley Syndrome, is an ultra-rare genetic disorder. As one of the first X-linked neurodevelopmental syndromes to be described, MCT8 deficiency was later associated with mutations in the SLC16A2 gene in 2004. The core mechanism driving the pathogenesis of MCT8 deficiency is dysfunction of the thyroid hormone transporter, monocarboxylate transporter 8 (MCT8). MCT8 has a major role in regulating thyroid hormone levels, including the cellular uptake and efflux of tri-iodothyronine (T3) and thyroxine (T4). MCT8 serves an important role in the transport of thyroid hormone across the blood–brain barrier and is also widely expressed in tissues in the thyroid, liver, kidneys, heart, and muscle. This disrupted thyroid hormone homeostasis leads to neurological and endocrinological symptoms. The neurological symptoms are a consequence of too little T3 in the brain during neurodevelopment, whereas the endocrinological symptoms are due to elevated T3 in other organs outside the brain.
Parents of children with MCT8 deficiency usually report the pregnancy and birth as uneventful, and infants appear to develop as expected for the first few months of life. Early signs, such as inadequate head control due to hypotonia and failure to thrive may start to appear from around three months of age, but it usually takes a few more months before medical attention is sought. Recognizing symptoms and making an early diagnosis may help patients and their families.
For further information about MCT8 deficiency, please see www.mct8deficiency.com
© Modular Finance, source