Dersimelagon in Erythropoietic Protoporphyrias
Manisha Balwani1, Herbert L Bonkovsky1, Cynthia Levy1
1From the Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York (M.B., R.J.D.); the Section on Gastroenterology and Hepatology, Wake Forest University-North Carolina Baptist Medical Center, Winston-Salem (H.L.B.); Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami (C.L.); the Division of Gastroenterology and Hepatology and the Porphyria Center, University of Texas Medical Branch, Galveston (K.E.A.); Liver Center and Porphyria Center, University of California, San Francisco, San Francisco (D.M.B.); the Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City (C.P.); Mitsubishi Tanabe Pharma Corporation, Tokyo (F.T.); and Mitsubishi Tanabe Pharma Development America, Jersey City, NJ (K.B.).
Dersimelagon significantly extended symptom-free sunlight exposure for patients with erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLPP). This novel treatment improved quality of life by increasing photoprotection against painful light reactions.
Area of Science:
- Biochemistry
- Genetics
- Dermatology
Background:
- Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLPP) are genetic disorders of heme biosynthesis.
- These conditions lead to elevated protoporphyrin levels and severe phototoxicity upon light exposure.
- Dersimelagon, a melanocortin 1 receptor agonist, aims to increase skin eumelanin for photoprotection.
Purpose of the Study:
- To evaluate the efficacy and safety of dersimelagon in patients with EPP and XLPP.
- To determine the effect of dersimelagon on the time to onset and severity of phototoxic symptoms.
- To assess the impact of dersimelagon on patient quality of life.
Main Methods:
- A randomized, placebo-controlled, phase 2 trial involving 102 patients (ages 18-75).
- Patients received placebo or dersimelagon (100 mg or 300 mg daily) for 16 weeks.
- Primary endpoint: change in time to first prodromal symptom of sunlight exposure; secondary endpoints included quality of life and safety.
Main Results:
- Dersimelagon significantly increased the mean daily time to the first symptom of sunlight exposure compared to placebo.
- The 100 mg and 300 mg dersimelagon groups showed mean increases of 53.8 and 62.5 minutes, respectively (P<0.01).
- Improvements in quality of life were observed, with nausea and skin hyperpigmentation being common adverse events.
Conclusions:
- Dersimelagon effectively increases the duration of symptom-free sunlight exposure in EPP and XLPP patients.
- The drug demonstrates a favorable safety profile at the tested doses.
- Dersimelagon represents a promising therapeutic option for managing phototoxicity in these rare genetic disorders.
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