Dersimelagon May Be Effective as Oral Treatment for Erythropoietic Protoporphyria

Article

New phase 2 data indicates safety and efficacy of dersimelagon, suggesting potential development as an oral treatment for erythropoietic protoporphyria and X-linked protoporphyria.

Dersimelagon may be efficacious and safe as a possible oral treatment option for enhancing light tolerance in those diagnosed with erythropoietic protoporphyria or X-linked protoporphyria, according to recent findings, thus warranting its continued development.1

These findings resulted from a phase 2 study examining both the efficacy and safety of dersimelagon, a newly-developed, selective melanocortin 1 receptor agonist which is orally administered.2

Activation of the melanocortin 1 receptor is known to offer photoprotection and antioxidative benefits, benefits which might shield those with erythropoietic protoporphyria or X-linked protoporphyria from harmful cell damage from sunlight.

As a result, this new research was conducted and it was authored by Kirstine Belongie, PhD, from Janssen Research & Development, Spring House in Pennsylvania.

“We conducted a randomized, multicenter, placebo-controlled, phase 2 trial to investigate the efficacy and safety of dersimelagon in patients with erythropoietic protoporphyria or X-linked protoporphyria,” Belongie and colleagues wrote.

Background and Findings

The investigators conducted a phase 2 trial with a randomized, placebo-controlled design, examining both the effectiveness and safety of dersimelagon in relation to the onset time and severity of symptoms experienced by patients with erythropoietic protoporphyria or X-linked protoporphyria when exposed to sunlight.

The study itself was conducted at 9 sites throughout the US, with a 2-week screening period prior to a 16-week period of treatment and a 6-week follow-up period being used in the study.

To qualify for participation in the trial, the participants had to meet certain criteria: they had to be between the ages of 18 - 75 and have a confirmed diagnosis of either erythropoietic protoporphyria or X-linked protoporphyria.

Study participants aged 18 - 75 were randomly assigned to 3 study arms: placebo, 100 mg dersimelagon, or 300 mg dersimelagon, with a 1:1:1 ratio. The treatment was administered by the investigators once daily for a duration of 16 weeks in total.

The research team’s main objective was to measure the change, from baseline to week 16, in the time it took for the first prodromal symptom associated with sunlight exposure to occur. For the team to capture relevant data, patients utilized an electronic diary to record daily sunlight exposure and symptom information.

Additionally, they assessed quality of life and ensured the safety of participants.

The investigators reported that, of the 102 patients who participated in the study and including 93 individuals with erythropoietic protoporphyria and 9 with X-linked protoporphyria, 90% successfully completed the treatment phase.

The average duration until the first prodromal symptom related to sunlight exposure was found to have shown a substantial increase with the use of dersimelagon. Comparing the change from baseline to week 16, the least-squares mean difference in the 100-mg dersimelagon group was 53.8 minutes (P = 0.008), while in the 300-mg dersimelagon group, it was 62.5 minutes (P = 0.003) when compared to the placebo arm.

The research team’s findings also showed an improvement in the quality of life for participants who received dersimelagon compared to those who were given the placebo. The most frequently reported adverse events during the treatment included freckles, nausea, headache, and hyperpigmentation of the skin.

“Results from this phase 2 trial support the effectiveness and safety of dersimelagon and its further development as a potential oral treatment option for increasing light tolerance in patients with erythropoietic protoporphyria or X-linked protoporphyria,” they wrote.

References

  1. 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. April 13, 2023. doi:10.1056/NEJMoa2208754.
  2. Suzuki T, Kawano Y, Matsumoto A, et al. Melanogenic effect of dersimelagon (MT-7117), a novel oral melanocortin 1 receptor agonist. Skin Health Dis 2021;2(1):e78-e78.
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