Dersimelagon in Erythropoietic Protoporphyrias

Manisha Balwani, Herbert L. Bonkovsky, Cynthia Levy, Karl E. Anderson, D. Montgomery Bissell, Charles Parker, Fumihiro Takahashi, Robert J. Desnick, Kirstine Belongie

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background Erythropoietic protoporphyria and X-linked protoporphyria are inborn errors of heme biosynthesis that cause elevated circulating levels of metal-free protoporphyrin and phototoxicity. Both disorders are characterized by excruciating phototoxic attacks after exposure to visible light. Dersimelagon is a new, orally administered, selective melanocortin 1 receptor agonist that increases levels of skin eumelanin. Methods We conducted a randomized, placebo-controlled, phase 2 trial to investigate the efficacy and safety of dersimelagon with respect to the time to onset and the severity of symptoms associated with sunlight exposure in patients with erythropoietic protoporphyria or X-linked protoporphyria. Patients 18 to 75 years of age were randomly assigned in a 1:1:1 ratio to receive placebo or dersimelagon at a dose of 100 or 300 mg once daily for 16 weeks. The primary end point was the change from baseline to week 16 in the time to the first prodromal symptom associated with sunlight exposure. Patients recorded daily sunlight exposure and symptom data in an electronic diary. Quality of life and safety were also assessed. Results Of the 102 patients (93 with erythropoietic protoporphyria and 9 with X-linked protoporphyria) who underwent randomization, 90% completed the treatment period. The mean daily time to the first prodromal symptom associated with sunlight exposure increased significantly with dersimelagon: the least-squares mean difference from placebo in the change from baseline to week 16 was 53.8 minutes in the 100-mg dersimelagon group (P=0.008) and 62.5 minutes in the 300-mg dersimelagon group (P=0.003). The results also suggest that quality of life improved in patients receiving dersimelagon as compared with placebo. The most common adverse events that occurred or worsened during treatment were nausea, freckles, headache, and skin hyperpigmentation. Conclusions At both doses evaluated, dersimelagon significantly increased the duration of symptom-free sunlight exposure in patients with erythropoietic protoporphyria or X-linked protoporphyria.

Original languageEnglish (US)
Pages (from-to)1376-1385
Number of pages10
JournalNew England Journal of Medicine
Volume388
Issue number15
DOIs
StatePublished - Apr 13 2023

Keywords

  • Dermatology
  • Dermatology General
  • Genetics
  • Genetics General
  • Neurology/Neurosurgery
  • Pain

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'Dersimelagon in Erythropoietic Protoporphyrias'. Together they form a unique fingerprint.

Cite this