- Treatment with LQT-1213 demonstrated statistically significant and clinically meaningful reductions in dofetilide-induced QTc prolongation.
- Larger treatment effects seen in pre-defined subgroups of individuals with largest increases in QTc from baseline and longest QTc intervals.
- No meaningful safety findings, including no effects on ECG morphology.
MONTREAL, March 26, 2024 /PRNewswire/ - Thryv Therapeutics is pleased to announce the presentation of its poster: SGK1 inhibitor LQT-1213 significantly attenuates dofetilide-induced QT prolongation in humans: Results of the WAVE I Clinical Study at the American College of Cardiology Conference. Thryv's poster presentation will be presented on Sunday, April 7th from 12:15 p.m. - 1:00 p.m. in Hall B4-5. Representatives from Thryv will also be present throughout the weekend to meet with cardiologists and electrophysiologists to gain insights into various elements of their development program strategies. To learn more about this initiative, please contact [email protected].
The WAVE I proof of concept clinical study evaluated LQT-1213 for the reduction of QTcF in individuals with dofetilide-induced long QT Syndrome ("LQTS"). LQT-1213 is a potent and selective inhibitor of Serum Glucocorticoid inducible Kinase 1 (SGK1), which is implicated in QTc prolongation. In the WAVE I study, following two days of treatment with dofetilide (baseline) – an agent known to prolong QTc – individuals with meaningful increases in their QTc interval received six days of increasing LQT-1213 doses with a consistent dose of dofetilide. Individuals were continuously monitored and received regular ECGs to assess the safety and efficacy of LQT-1213. Mean reductions of QTcF from baseline (measured as QTcF) were statistically significant beginning with the first evaluable time point of the primary analysis and were sustained during the peak dofetilide-induced prolongation.
In a predefined subset of individuals who experienced larger dofetilide-induced prolongation of QTcF, individuals treated with LQT-1213 achieved more robust, clinically meaningful reductions of QT consistent with scientific evidence of SGK1 activation in LQTS. LQT-1213 was well tolerated with no serious adverse events or treatment-related study discontinuations. No QTcF over-shortening was observed in the study. There were no observed changes in ECG morphology, heart rate or blood pressure.
Part 2 of the WAVE I clinical study is currently enrolling a small cohort of individuals with genetically confirmed congenital Long QT Syndrome Type 2 and Type 3. This study will provide information about the safety of LQT-1213 before initiation of Phase 3 clinical studies in congenital LQTS patients. Data from this study is expected in the second quarter of 2024. More about the WAVE I (Parts 1 and 2) can be found at https://www.clinicaltrials.gov/study/NCT05906732.
Long QT Syndrome, or LQTS, is a disorder of the heart's electrical system causing the lower chambers of the heart to contract and release too slowly. LQTS can be either congenital or acquired. Congenital LQTS is a set of rare orphan diseases in which people are genetically predisposed to chronic prolongation of their QTc interval (commonly more than 480 milliseconds), leading to increased risk of torsades de pointes, a lethal cardiac arrhythmia that causes sudden cardiac death. Acquired Long QT may develop from the administration of therapies which block electrical pathways in the heart, leading to a similar mechanistic prolongation of QT and risk of sudden cardiac death.
Thryv Therapeutics Inc. is a privately owned company based in Montreal, Quebec, Canada. Thryv Therapeutics is pioneering a precision medicine approach to treat indications including Congenital Long QT Syndromes (LQTS), atrial fibrillation and heart failure, with potent and selective inhibitors of Serum Glucocorticoid inducible Kinase (SGK1).
SOURCE Thryv Therapeutics Inc.
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