A physician-turned-patient's unique perspective has helped shape the development of the first approved treatment for a rare genetic light sensitivity disorder, marking a significant advancement in patient-involved drug development.
Dr. Jasmin Barman-Aksözen's journey began with unexplained painful burns on her skin, leading to her self-diagnosis of erythropoietic protoporphyria (EPP) through Wikipedia research, later confirmed by her physician. EPP, an ultra-rare genetic condition, causes severe burn injuries after brief exposure to visible light due to the accumulation of phototoxic heme precursors in red blood cells.
"There was no cure, there was no therapy for the pain, and there were no preventive possibilities for this phototoxic reaction," Barman-Aksözen explained. "The only thing we could do was avoid visible light. As you can imagine, that's socially very isolating, and it's not compatible with a normal life, and having to avoid light also leads to depression."
Breakthrough Treatment Development
During this time, Clinuvel Pharmaceuticals was developing afamelanotide (Scenesse), a slow-release treatment designed to increase skin pigmentation and provide anti-inflammatory protection against light-induced skin damage. Barman-Aksözen joined a University of Zurich research group working on Scenesse as a PhD student, contributing valuable insights on clinical trial design and quality of life measures.
The pivotal Phase III trial (NCT01605136) yielded promising results: patients receiving Scenesse gained an average of 20 additional minutes of pain-free sun exposure daily compared to placebo recipients. Some patients could achieve up to three hours of daily sun exposure while on treatment, with reduced frequency, intensity, and duration of phototoxic reactions.
Historic Regulatory Approval
In 2014, Scenesse received European approval, with Barman-Aksözen making history as the first patient to present directly to the European Medicines Agency (EMA) committee before their approval vote. This milestone marked the first drug approved through EMA's pilot program incorporating patient and physician clinical experiences in regulatory decisions. The FDA followed with its approval in 2019.
Current Challenges and Future Directions
Despite Scenesse's success, limitations persist. "As a fixed-dose implant for symptomatic relief, it's not scalable and cannot be used for children," Barman-Aksözen noted. New therapeutic candidates are under development, including Mitsubishi's dersimelagon and Disc Medicine's bitopertin.
These ongoing clinical trials face unique ethical challenges, including the risk of phototoxic burns in control groups and potential selection bias, as severely affected patients may be reluctant to participate. Barman-Aksözen, who co-founded the International Porphyria Patient Network (IPPN), advocates for comprehensive evaluation of new treatments: "As patients, we've requested head-to-head studies. Besides the ethical aspects, I, as a patient, want to know how a new substance compares not only to placebo but also to the existing therapy."
