Dersimelagon increases duration of symptom-free sunlight exposure in erythropoietic protoporphyria: NEJM

The researchers also observed improved quality of life among patients receiving dersimelagon compared to placebo.

X-linked protoporphyria and erythropoietic protoporphyria are inborn disorders in which heme biosynthesis is disrupted, causing increased circulating levels of metal-free protoporphyrin and phototoxicity. The diseases are characterized by severe phototoxic attacks following exposure to bright sunlight. Dersimelagon is a new, orally administered, selective melanocortin 1 receptor agonist that raises levels of skin eumelanin.

In their study published in the New England Journal of Medicine, Manisha Balwani from Icahn School of Medicine at Mount Sinai in New York and colleagues aimed to investigate the safety and efficacy of dersimelagon concerning the onset time and the severity of symptoms linked with sunlight exposure in patients with X-linked protoporphyria or erythropoietic protoporphyria.

The trial involved patients 18 to 75 years of age who were randomly assigned in a ratio of 1:1:1 to receive a placebo or dersimelagon for 16 weeks at a dose of 100 or 300 mg once daily. A change in the time to the first prodromal symptom associated with exposure to sunlight from baseline to week 16 was determined (primary endpoint). Recording of patients' daily sunlight exposure and symptom data was done in an electronic diary. Safety and quality of life were also assessed.

The study led to the following findings:

• Of the 102 patients (93 with erythropoietic protoporphyria and 9 with X-linked protoporphyria) who underwent randomization, 90% completed the treatment period.
• There was a significant increase in the mean daily time to the first prodromal symptom linked with sunlight exposure 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 and 62.5 minutes in the 300-mg dersimelagon group.
• The results also suggest that quality of life improved in patients receiving dersimelagon compared to placebo.
• The most common adverse events that occurred or worsened during treatment were freckles, nausea, headache, and skin hyperpigmentation.

The researchers conclude, "At both doses evaluated, dersimelagon remarkably increased the duration of symptom-free sunlight exposure in patients with X-linked protoporphyria or erythropoietic protoporphyria."

Reference:

Balwani M, Bonkovsky HL, Levy C, Anderson KE, Bissell DM, Parker C, Takahashi F, Desnick RJ, Belongie K; Endeavor Investigators. Dersimelagon in Erythropoietic Protoporphyrias. N Engl J Med. 2023 Apr 13;388(15):1376-1385. doi: 10.1056/NEJMoa2208754. PMID: 37043653.