Results from a first-in-human study of dersimelagon, an investigational oral selective MC1R agonist

Eur J Clin Pharmacol. 2023 Jun;79(6):801-813. doi: 10.1007/s00228-023-03476-6. Epub 2023 Apr 15.


Purpose: To describe outcomes from the first-in-human study of dersimelagon, an investigational oral selective MC1R agonist, under development for the treatment of erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP).

Methods: In this double-blind, placebo-controlled phase 1 study, the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral doses of dersimelagon in healthy participants were evaluated.

Results: Dersimelagon was generally well tolerated in healthy participants, with the most common TEAEs being lentigo (52.8%) and skin hyperpigmentation (50.0%) after multiple doses. Systemic exposure to dersimelagon in plasma (based on AUC0-∞ and Cmax) increased in a slightly more than dose-proportional manner over the 1- to 600-mg single-dose range. Following multiple doses, dersimelagon was rapidly absorbed (median Tmax ranging from 4 to 5 h postdose on days 1 and 14). Mean t1/2 ranged from 10.56 to 18.97 h on day 14, and the steady state of plasma concentration was generally reached by 5 days of multiple dosing. There were no observable effects of age or race on the PK profile of dersimelagon or its metabolite dersimelagon glucuronide. No treatment-related effects on melanin density (MD) were observed following single doses of dersimelagon; however, after multiple doses, increases in MD were observed in participants receiving 150 and 300 mg dersimelagon.

Conclusion: Our study results indicate that dersimelagon is generally well tolerated and demonstrates a generally consistent PK profile across diverse subgroups. Treatment-related increases in MD warrant further investigation in a larger study population and in patients with EPP and XLP.

Trial registration: A Study to Investigate the Safety, Tolerability and Pharmacokinetics of MT-7117 in Healthy Subjects, NCT02834442, , registration began July 2016.

Keywords: Dersimelagon; Erythropoietic protoporphyria; First-in human; Melanin density; X-linked protoporphyria.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Area Under Curve*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Healthy Volunteers
  • Humans

Associated data