Afamelanotide for Erythropoietic Protoporphyria

This publication in the New England Journal of Medicine presented the results of two phase 3 multicenter randomized placebo-controlled clinical trials evaluating the efficacy of afamelanotide (Scenesse) in patients with erythropoietic protoporphyria (EPP), a rare disease that causes intense pain and severe burns even with minimal sun exposure. Together, the studies included 168 patients.

Participants received 16 mg subcutaneous afamelanotide implants (slow-release formulation) or placebo every 60 days. The primary endpoint was the duration of direct sun exposure without pain, measured by electronic diaries completed by patients.

The results demonstrated that patients treated with afamelanotide were able to remain significantly longer in the sun without pain compared to placebo. In the European study (CUV039), the median hours of pain-free sun exposure was substantially higher in the treated group. Patients also reported improved quality of life and less need to avoid sunlight.

Afamelanotide works by increasing the production of eumelanin in the skin, which absorbs phototoxic porphyrins and protects against tissue damage caused by light-activated protoporphyrins. These results led to the approval of Scenesse by the EMA (2014) and later by the FDA (2019) as the first and only approved treatment for EPP, a disease that previously had no specific pharmacological therapy.