Exploring Afamelanotide for Vitiligo: Insights into the CUV 105 Phase 3 Clinical Trial

Tareen Dermatology recently announced a partnership with pharmaceutical company CLINUVEL. The partnership is intended to advance vitiligo research through the undertaking of advanced-stage clinical trials.¹

One such clinical trial is the phase 3 CUV 105 trial assessing the efficacy and safety of afamelanotide (Scenesse) in combination with phototherapy for treating vitiligo, which is actively recruiting participants at multiple study sites across the US.²

Image Credit: © Ilnur - stock.adobe.com

Background on Afamelanotide

Afamelanotide, a synthetic analog of alpha-melanocyte-stimulating hormone (α-MSH), functions as a melanocortin-1 receptor (MC1R) agonist. By stimulating MC1R, it promotes the production of eumelanin, the pigment responsible for skin coloration.³

Afamelanotide was first approved for use in erythropoietic protoporphyria in the United States in 2019. Its previous clinical application has been limited to specialized porphyria clinics, but the drug has demonstrated a robust safety profile with over 12,000 uses and no reported life-threatening events directly attributable to the medication.⁴

Study Design and Objectives

The CUV 105 clinical trial is a phase 3, multicentric, randomized, controlled study designed to evaluate the efficacy and safety of afmelanotide in combination with narrowband ultraviolet B (NB-UVB) phototherapy for treating vitiligo. Its primary objective is to assess whether the combination therapy results in superior repigmentation compared to NB-UVB monotherapy.

The study targets patients with Fitzpatrick skin types IV to VI. This inclusion criterion is based on prior research indicating more significant repigmentation in darker skin types.

Participants will be randomized into 2 treatment groups: a combination therapy and monotherapy group. The combination therapy group will receive NB-UVB phototherapy alongside afamelanotide administered as a subcutaneous implant (16 mg) every 3 weeks for a total of 5 months. This regimen includes 7 implants. The monotherapy group will receive only NB-UVB phototherapy over the same period.

The study will utilize the Vitiligo Area Scoring Index (VASI) to measure repigmentation.

Key Findings from Previous Studies

A previous phase 2 study compared afamelanotide combined with NB-UVB phototherapy against phototherapy alone.

The combination therapy group demonstrated a higher percentage of patients with significant repigmentation on the face and upper extremities compared to the phototherapy-only group. Repigmentation 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.

Current Study Updates and Future Directions

The CUV 105 trial is expanding upon previous research by increasing the afamelanotide dosage and extending the observation period.

The ongoing study features an increased dosage, with afamelanotide administered at a higher dose (16 mg) compared to previous trials. An additional 6-month follow-up period post-treatment aims to assess the durability of repigmentation and monitor for any potential relapse or adverse effects.

Patients must have Fitzpatrick types IV to VI and extensive vitiligo affecting both the face and body. Exclusion criteria includes recent phototherapy, history of skin cancer, and severe liver disease.

Challenges and Considerations

While the study holds promise, several challenges remain.

Identifying patients with the requisite severity of vitiligo poses a challenge. Strict inclusion and exclusion criteria can limit participant eligibility.

The potential for diffuse hyperpigmentation as an adverse effect may be culturally sensitive in some populations. Awareness and education about the side effects are crucial in managing patient expectations and ensuring informed consent.

The durability of repigmentation beyond the treatment period remains a key area of interest. Ongoing monitoring will be critical to determine the long-term benefits and any need for additional treatments.

Involvement

As Tareen Dermatology and CLINUVEL are still actively recruiting participants for the trial, clinicians interested in becoming involved or referring eligible patients are encouraged to visit Tareen Dermatology's website or contact director of research and clinical research coordinator, Cameron Kurisko.

References

1. Tareen Dermatology partners with CLINUVEL for clinical trials on groundbreaking vitiligo treatment. News release. PR Newswire. August 23, 2024. Accessed September 5, 2024. https://www.prnewswire.com/news-releases/tareen-dermatology-partners-with-clinuvel-for-clinical-trials-on-groundbreaking-vitiligo-treatment-302229529.html
2. ClinicalTrials.gov. A study to compare the efficacy and safety of SCENESSE and narrow-band ultraviolet (NB-UVB) light versus NB-UVB light alone in patients with vitilig. Identifier NCT06109649. Accessed September 5, 2024. https://clinicaltrials.gov/study/NCT06109649?cond=scenesse&aggFilters=status:rec&rank=2
3. Polańska A, Wegner J, Nutbohm P, et al. Afamelanotide in protoporphyria and other skin diseases: a review. Postepy Dermatol Alergol. 2024;41(2):149-154. doi:10.5114/ada.2024.138818
4. FDA approves first treatment to increase pain-free light exposure in patients with a rare disorder. News release. US FDA. October 8, 2019. Accessed September 5, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-increase-pain-free-light-exposure-patients-rare-disorder
5. A study to assess the changes in pigmentation and safety of afamelanotide in patients with vitiligo. CTV. Accessed September 5, 2024. https://ctv.veeva.com/study/a-study-to-assess-the-changes-in-pigmentation-and-safety-of-afamelanotide-in-patients-with-vitiligo