Phase 1 Evaluation of the Pharmacokinetics of Sevasemten (EDG-5506) for Potential Food Effect and Drug-Drug Interaction With a CYP3A4 Moderate Inhibitor.
- 1Edgewise Therapeutics, Inc., Boulder, Colorado, USA.
Abstract
Sevasemten (EDG-5506) is an investigational, small molecule, in development for the treatment of Becker and Duchenne muscular dystrophy. In vitro data suggest sevasemten is a substrate for cytochrome P450 (CYP)3A4. Here, we investigate whether the pharmacokinetics (PK) of sevasemten are affected when co-administered with a moderate CYP3A4 inhibitor, verapamil. The impact of a high-fat meal on the PK of sevasemten was also investigated. This Phase 1, open-label, parallel study of healthy subjects dosed three unique cohorts (sevasemten alone, sevasemten co-administered with verapamil, and sevasemten under fed conditions). Administration of a single dose of sevasemten with daily dosing of verapamil had no significant effect on the maximum concentration (Cmax) or area under the plasma concentration-time curve (AUC) of sevasemten compared to a single dose of sevasemten under fasted conditions (Geometric mean ratios of 101.6% and 97.5%, respectively), indicating that the PK of sevasemten may not be influenced by verapamil, a moderate CYP3A4 inhibitor. Administration of a single dose of sevasemten under fed conditions increased the AUCs of sevasemten by 20% to 38%, while the Cmax remained comparable to that under fasted conditions. Together, these data support allowing patients who benefit from sevasemten to also use a moderate CYP3A inhibitor without dose modification and support administration of sevasemten without regard to food intake.
Related
- Pharmacokinetics and Safety Evaluation of the Transglutaminase 2 Inhibitor Suvigletistat in Healthy Chinese, Japanese, and White/European Participants.
- Design and Synthesis of New Thiazole Derivatives for Alzheimer’s Disease Therapy as a Potential Cholinesterase Inhibitor; Toxicity Prediction and Molecular Docking Studies and Biological Evaluation
- Characterizing the Metabolic Fate and Pharmacokinetics of the RyR2 Inhibitor ent-Verticilide
- Safety, Tolerability, and Pharmacokinetics of EGT710, a Novel Coronavirus Mpro Inhibitor, in Healthy Adults: A Randomized, Single- and Multiple-Dose Study.
- A First-in-Class, Brain-Penetrant Small Molecule Inhibitor of the NOS1AP-Tau Interaction Rescues Tau Pathology In Vivo and Improves Cognition
BibTeX
@article{madden2026phase,
title = {{Phase 1 Evaluation of the Pharmacokinetics of Sevasemten (EDG-5506) for Potential Food Effect and Drug-Drug Interaction With a CYP3A4 Moderate Inhibitor.}},
author = {Molly Madden and Roxana Donisa Dreghici and Jeffrey A Silverman},
journal = {Clinical and translational science},
year = {2026},
month = nov,
doi = {10.1111/cts.70751},
url = {https://europepmc.org/article/MED/42974700},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Phase 1 Evaluation of the Pharmacokinetics of Sevasemten (EDG-5506) for Potential Food Effect and Drug-Drug Interaction With a CYP3A4 Moderate Inhibitor.
AU - Molly Madden
AU - Roxana Donisa Dreghici
AU - Jeffrey A Silverman
PY - 2026
DA - 2026/11/01
JO - Clinical and translational science
DO - 10.1111/cts.70751
UR - https://europepmc.org/article/MED/42974700
AB - Sevasemten (EDG-5506) is an investigational, small molecule, in development for the treatment of Becker and Duchenne muscular dystrophy. In vitro data suggest sevasemten is a substrate for cytochrome P450 (CYP)3A4. Here, we investigate whether the pharmacokinetics (PK) of sevasemten are affected when co-administered with a moderate CYP3A4 inhibitor, verapamil. The impact of a high-fat meal on the PK of sevasemten was also investigated. This Phase 1, open-label, parallel study of healthy subjects dosed three unique cohorts (sevasemten alone, sevasemten co-administered with verapamil, and sevasemten under fed conditions). Administration of a single dose of sevasemten with daily dosing of verapamil had no significant effect on the maximum concentration (Cmax) or area under the plasma concentration-time curve (AUC) of sevasemten compared to a single dose of sevasemten under fasted conditions (Geometric mean ratios of 101.6% and 97.5%, respectively), indicating that the PK of sevasemten may not be influenced by verapamil, a moderate CYP3A4 inhibitor. Administration of a single dose of sevasemten under fed conditions increased the AUCs of sevasemten by 20% to 38%, while the Cmax remained comparable to that under fasted conditions. Together, these data support allowing patients who benefit from sevasemten to also use a moderate CYP3A inhibitor without dose modification and support administration of sevasemten without regard to food intake.
SN - 1752-8054
SN - 1752-8062
ER -