Better Outcomes of Erythropoietic Protoporphyria Seen With Afamelanotide Use

By Will Boggs MD

March 30, 2020

NEW YORK (Reuters Health) - Afamelanotide treatment is associated with improved clinical outcomes and quality of life in patients with erythropoietic protoporphyria (EPP), according to a Dutch study.

"Offer this to your patients when financially possible; it is a life changer," Dr. Janneke G. Langendonk of Erasmus MC, University Medical Center, in Rotterdam, told Reuters Health by email.

EPP is a rare inherited disorder of heme biosynthesis resulting from mutations in FECH or ALAS2. It causes painful photosensitivity. Afamelanotide is a potent alpha-melanocyte-stimulating hormone (a-MSH) analog that increases eumelanin and stimulates anti-inflammatory and antioxidative pathways.

Dr. Langendonk and colleagues investigated the outcomes of afamelanotide treatment in their single-center, single-arm prospective postauthorization safety and efficacy study of 117 patients with EPP.

Patients received a controlled-release 16-mg subcutaneous implant of afamelanotide with an interval of at least 60 days and a maximum of four implants per year.

In week 1, time spent outside rose a mean 1.85 hours per week with afamelanotide (P=0.06). By week 5, time spent outside had increased an average of 6.14 hours per week (P<0.001).

Time spent outside increased an average of 1.4 hours per week per year on treatment (P=0.04), the researchers report in JAMA Dermatology.

EPP quality-of-life improved by 14% with afamelanotide treatment, an improvement that increased with patient age.

The number of phototoxic reactions initially increased during afamelanotide treatment but decreased thereafter as patients tried to identify their new light-exposure limit.

The most common adverse events were nausea, fatigue/malaise, flushing and nausea with headache, all of which were self-limiting with a mean duration of one to two days directly after implantation. There were no treatment-related serious adverse events.

Responses to therapy varied considerably between individual patients, and the current recommended dosing schedule of afamelanotide was insufficient for several patients.

"Erythropoietic protoporphyria is not cured by afamelanotide, and despite the improvement, sunlight exposure restrictions remain," the authors note.

"New and other a-MSH analogues should not be studied in placebo-controlled trials; that is cruel!" Dr. Langendonk said. "It should be head-to-head trials."

Dr. Manisha Balwani of Icahn School of Medicine at Mount Sinai, in New York City, who studies porphyria but was not involved in the new work, told Reuters Health by email, "The most interesting finding is that patients responded to the drug regardless of baseline disease severity and that the effects improved over years of treatment."

"Afamelanotide does not address the elevated protoporphyrin level or the ferrochelatase-enzyme deficiency," she explained. "It does not have any impact on liver disease in EPP."

"There is a lot of clinical variability in EPP, and each patient will respond differently," Dr. Balwani said. "The patients who have the mildest disease manifestations at baseline will be most likely to have the best response."

Afamelanotide was approved by the European Medicines Agency in 2016 and by the U.S. Food and Drug Administration in 2019.

Dr. Langendonk and two of his coauthors report financial ties to Clinuvel Pharmaceuticals, which markets afamelanotide as Scenesse.

SOURCE: JAMA Dermatology, online March 18, 2020.