The phase 3 CUV 105 clinical trial is currently underway to assess the efficacy and safety of afamelanotide (Scenesse) in combination with narrowband ultraviolet B (NB-UVB) phototherapy for the treatment of vitiligo. This multicenter, randomized, controlled study is actively recruiting participants across the US to determine if the combination therapy results in superior repigmentation compared to NB-UVB monotherapy.
Afamelanotide and its Mechanism of Action
Afamelanotide is a synthetic analog of alpha-melanocyte-stimulating hormone (α-MSH) and functions as an agonist of the melanocortin-1 receptor (MC1R). Stimulation of MC1R leads to the production of eumelanin, the pigment responsible for skin coloration. Originally approved for erythropoietic protoporphyria in 2019, afamelanotide has a well-established safety profile with over 12,000 uses and no reported life-threatening events directly attributed to the drug.
CUV 105 Trial Design
The CUV 105 trial is designed to evaluate afamelanotide in combination with NB-UVB phototherapy for treating vitiligo. Eligible participants are those with Fitzpatrick skin types IV to VI, based on prior research indicating more significant repigmentation in darker skin types. Participants are randomized into two treatment groups: a combination therapy group and a monotherapy group. The combination therapy group receives NB-UVB phototherapy alongside afamelanotide, administered as a subcutaneous implant (16 mg) every three weeks for five months, totaling seven implants. The monotherapy group receives only NB-UVB phototherapy over the same period. Repigmentation is measured using the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF) scores.
Prior Clinical Evidence
Data from a previous phase 2 study showed that afamelanotide combined with NB-UVB phototherapy resulted in a higher percentage of patients achieving significant repigmentation on the face and upper extremities compared to phototherapy alone. Repigmentation also occurred more rapidly in the combination therapy group. Both VASI and VETF scores indicated significantly better outcomes for patients receiving afamelanotide plus phototherapy versus those receiving phototherapy alone. Notably, patients with Fitzpatrick skin types IV to VI showed improved results compared to those with type III. Common adverse effects included erythema (68% in combination therapy vs. 82% in monotherapy) and diffuse hyperpigmentation. The latter was a universal effect due to melanocyte stimulation. Other reported effects included nausea (18% of patients) and pruritus.
Enhancements in the Current Study
The CUV 105 trial builds upon previous research by increasing the afamelanotide dosage and extending the observation period. The current study uses a higher dose of afamelanotide (16 mg) compared to previous trials. An additional six-month follow-up period post-treatment aims to assess the durability of repigmentation and monitor for any potential relapse or adverse effects. Key inclusion criteria include Fitzpatrick types IV to VI and extensive vitiligo affecting both the face and body. Exclusion criteria include recent phototherapy, a history of skin cancer, and severe liver disease.
Challenges and Future Considerations
Despite the promise of the study, several challenges remain. Identifying patients with the requisite severity of vitiligo poses a challenge due to strict inclusion and exclusion criteria that can limit participant eligibility. The potential for diffuse hyperpigmentation as an adverse effect may be culturally sensitive in some populations, necessitating awareness and education about the side effects to manage patient expectations and ensure informed consent. The durability of repigmentation beyond the treatment period remains a key area of interest, and ongoing monitoring will be critical to determine the long-term benefits and any need for additional treatments.
