Product information and disease description Place of product in therapy Approaches to treatment

Expected outcomes of therapy

4 evidence topics · 4 sources

Summary: outcomes a melanocortin 1 receptor agonist is expected to change

Therapy with a melanocortin 1 receptor agonist is symptomatic. It is expected to increase the time a patient can spend in sunlight before symptoms begin, reduce the number of sunlight-induced pain events, and improve patient-reported global impression and quality of life. It is not expected to lower protoporphyrin concentrations or to alter the risk of protoporphyric hepatopathy, and sunlight protection measures continue during treatment. The regulatory precedent for the approved comparator used hours of direct sunlight exposure without pain as the primary endpoint; the dersimelagon program instead used minutes of daily sunlight exposure before the first prodromal symptom, so effect sizes are not directly comparable between the two products.

Endpoint accepted for the approved comparator

“The primary efficacy end point was the number of hours of direct exposure to sunlight without pain.” (opens the source at this quote in a new tab)

Pain as the clinically meaningful outcome in a symptomatic therapy

“Being a symptomatic treatment, afamelanotide does not affect quantifiable biomarkers or objectively quantifiable disease signs in EPP. However, a “reduction in pain” is clinically meaningful and the extend of the provided benefit can be assessed by the patients themselves, as opposed to, for example, surrogate endpoints that measure change in biomarker expression” (opens the source at this quote in a new tab)

Differences in endpoints prevent cross-product comparison

“The primary endpoints used in the clinical trials investigating dersimelagon, bitopertin and cimetidine differ from each other, and from the endpoint used in the pivotal trial investigating afamelanotide in EPP. While some of the secondary endpoints assess the same aspects, the exact methods how the results were obtained need to be considered when comparing efficacy outcomes between the different interventions.” (opens the source at this quote in a new tab)