Arrhythmias & electrophysiologyDiagnostic or prognostic study
Targeting trafficking defects in long QT syndrome type 2: a phase 2 clinical study with patient-specific cellular validation
- Single-arm phase 2 clinical study
- patient-specific hiPSC-CM validation
Authors' conclusion
Short-term LUM therapy is safe and yields a significant QTc shortening in LQT2 patients with a trafficking defect.
Study context
- Population
- Adults with LQT2 and genetically confirmed trafficking-defective KCNH2 variants
- Participants
- 16 adults
- Outcome
- QTc shortening
- Follow-up
- 7 days
Performance
As reported in the abstract
QTc change
Significant QTc shortening with lumacaftor
P < .001
Per-patient QTc change, mean ± SD
31 ± 21 ms
Further findings
QTc reduction ≥40 ms, baseline QTc ≥500 ms (subgroup)
- Patients with baseline QTc ≥500 ms achieving reductions ≥40 ms
- 75%
hERG trafficking in hiPSC-CMs
- Lumacaftor (LUM) restored hERG trafficking in variants
- three out of five
- mirroring the clinical observations
Safety
Ventricular arrhythmias and adverse effects
- No ventricular arrhythmias occurred
- Adverse effects primarily gastrointestinal and self-limited
Original publication
Targeting trafficking defects in long QT syndrome type 2: a phase 2 clinical study with patient-specific cellular validation. Eur Heart J. Published 22 September 2026. doi:10.1093/eurheartj/ehag753
Summarised from the published abstract; every number is checked against it