EMC survival study

16 evidence topics · 5 sources

Objective

Survival objective

“As thyrotoxicosis is linked to increased mortality, we investigated whether Triac treatment could improve survival in paediatric and adult male patients with MCT8 deficiency.” (opens the source at this quote in a new tab)
“We investigated the effects of Triac on all-cause mortality in patients with MCT8 deficiency.” (opens the source at this quote in a new tab)

Location and study date

International data collection

“Genetic, clinical, biochemical and treatment data were collected from 173 sites in 48 countries through an international consortium on MCT8 deficiency, including patients that were in the Triac Trial I, a cohort of patients being part of the tiratricol managed access program, and published cases in the literature.” (opens the source at this quote in a new tab)
“Results from the study, will be presented as an oral presentation by Dr Floor van der Most on September 8, 2024, at the 46th Annual Meeting of the European Thyroid Association, in Athens, Greece.” (opens the source at this quote in a new tab)

Study design

Retrospective real-world cohort design

“This retrospective international real-world cohort study investigated the effects of tiratricol on all-cause mortality in patients with MCT8 deficiency.” (opens the source at this quote in a new tab)

Sponsor analysis of the Erasmus University Medical Center cohort

“The pre-NDA meeting was held on the back of the Breakthrough Therapy Designation granted in July 2025, based on FDA’s review of Egetis’ analysis of survival data from the international cohort study conducted by Erasmus University Medical Center (the EMC Survival Study).” (opens the source at this quote in a new tab)

Eligibility criteria

Exclusion criteria and mutation classification

“The impact of mutations on MCT8 transporter function was assessed in transfected cells and classified as mild, moderate or severe loss-of-function (LoF).” (opens the source at this quote in a new tab)
“Patients were excluded because (i) they were born before the disease’s discovery in 2004 (n=152), (ii) limited data (n=68) or (iii) unknown LoF (n=36).” (opens the source at this quote in a new tab)

Treatment

No evidence found.

Study outcomes

Rationale for using all-cause mortality as the primary endpoint

Mortality in MCT8 deficiency and the link to thyrotoxicosis

“Mortality rates in MCT8 deficiency are high with 30% dying during childhood. The T3 analogue triiodothyroacetic acid (Triac) has been proven to safely alleviate peripheral thyrotoxicosis in patients with MCT8 deficiency. As thyrotoxicosis is linked to increased mortality, we investigated whether Triac treatment could improve survival in paediatric and adult male patients with MCT8 deficiency.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Screened and included populations in the congress analysis

“We screened 484 males with MCT8 deficiency of whom 228 were included.” (opens the source at this quote in a new tab)
“Baseline characteristics between Triac-treated (n=111) and untreated patients (n=117) were similar, except for untreated patients residing less often in Western countries (57 vs 78%).” (opens the source at this quote in a new tab)

Study size reported in the New Drug Application

“The Priority Review highlights the robust dataset we have in this rare genetic disease, with the NDA based on results from Triac Trial I (46 patients), Triac Trial II (22 patients), ReTRIACt (15 patients), EMC Cohort Study (67 patients), EMC Survival Study (>600 patients) and the U.S. Expanded Access Program (approximately 40 patients included in the NDA).” (opens the source at this quote in a new tab)

Description of analysis sets

Baseline comparisons, missing data, and survival models

“Baseline characteristics, including age at symptom onset, age at diagnosis, country of residency, LoF, disease features, presence of a feeding tube, and prior treatment aiming to alleviate thyrotoxicosis were compared using Mann-Whitney U and Chi-Square test (5% level of significance).” (opens the source at this quote in a new tab)
“Missing data were imputed with multiple imputation prior to Kaplan-Meier, Log-rank, and Cox proportional-hazards models carried out to estimate the effect of Triac on survival.” (opens the source at this quote in a new tab)

Results

Participant disposition

Screening, exclusion, and follow-up

“We screened 484 males with MCT8 deficiency of whom 228 were included.” (opens the source at this quote in a new tab)
“Patients were excluded because (i) they were born before the disease’s discovery in 2004 (n=152), (ii) limited data (n=68) or (iii) unknown LoF (n=36).” (opens the source at this quote in a new tab)
“Median follow-up after diagnosis was 4.8 years [IQR=2.7–8.4] and we observed 32 deaths (5 treated vs 27 untreated).” (opens the source at this quote in a new tab)

Baseline characteristics

Comparison of treated and untreated participants

“Baseline characteristics between Triac-treated (n=111) and untreated patients (n=117) were similar, except for untreated patients residing less often in Western countries (57 vs 78%).” (opens the source at this quote in a new tab)

Efficacy results

All-cause mortality: congress analysis

“Median follow-up after diagnosis was 4.8 years [IQR=2.7–8.4] and we observed 32 deaths (5 treated vs 27 untreated).” (opens the source at this quote in a new tab)
“No other baseline characteristics did significantly affect survival or the effect of Triac treatment.” (opens the source at this quote in a new tab)
“In this international real-world cohort study, we showed that Triac treatment in paediatric and adult patients with MCT8 deficiency was associated with a 3-times lower risk on mortality.” (opens the source at this quote in a new tab)

All-cause mortality: hazard ratio

“Tiratricol-treated patients had an approximately three times lower risk of all-cause mortality (Hazard Ratio= 0.28, 95% Confidence Interval= 0.09–0.91, p-value <0.05).” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

No evidence found.

Study limitations

Summary

The congress analysis included 228 of 484 screened participants and compared 111 treated participants with 117 untreated participants; it reported 5 versus 27 deaths over a median follow-up of 4.8 years after diagnosis. Treatment was not randomized, and the treated and untreated groups differed in the proportion residing in Western countries (78% versus 57%). The reported hazard ratio (0.28, 95% CI 0.09 to 0.91) is an observational association; the authors state that confounding and immortal time bias remain potential threats to validity and that further analyses were ongoing. Missing data were handled by multiple imputation. Later manufacturer documents describe the EMC Survival Study as including more than 600 participants, while the only quoted estimate comes from the 228-participant congress analysis. As of the second-quarter 2026 interim report, the survival data had not yet been published in a peer-reviewed journal.

Authors' statement on residual bias

“To verify the robustness of our results, ongoing analyses aim to minimize confounding and immortal time bias, which pose potential threats to validity in cohort studies.” (opens the source at this quote in a new tab)

Publication status of the survival data

“In Italy and France, we plan to strengthen our value dossiers with survival data for Emcitate, once it has been published in a peer-reviewed journal by Erasmus Medical Center.” (opens the source at this quote in a new tab)