Afamelanotide: Coloring the Future of Vitiligo Treatment
Authors: Akash Rau, BS,1 Faranak Kamangar, MD2
Key Points
- Afamelanotide, a structural analog of α-melanocyte stimulating hormone, significantly accelerated repigmentation in patients with vitiligo in the CUV105 clinical trial.
- Time to onset of repigmentation was as early as day 21 with some patients having spontaneous repigmentation months after treatment.
- Combination with NB-UVB therapy has led to faster and more effective repigmentation compared to NB-UVB alone, demonstrating the promising potential of this therapeutic.
How does this work highlight an innovative perspective in dermatology?
Afamelanotide is the first systematic therapy targeting MC1R to stimulate melanogenesis. It is unique as it provides controlled, sustained drug delivery through a subcutaneous implant. This medication represents a shift toward biologic-based treatments for pigmentary disorders.
Afamelanotide is a structural analogue of α-melanocyte stimulating hormone (α-MSH).1-4 It is primarily available as a 16 mg bioresorbable subcutaneous controlled-release implant. It binds and activates MC1R which leads to melanogenesis and melanocyte proliferation.2-4 Other properties include cytoprotective antioxidant effects and anti-inflammatory capabilities.2-4
CUV105 is a phase III, double arm, open label clinical study with 200 participants. Inclusion criteria included adults and adolescents aged 12 and up, generalized vitiligo of the face and body (Total Vitiligo Area Scoring Index (T-VASI) ≥3), and Fitzpatrick skin types III-VI. The primary endpoint was T-VASI50 (excluding the hands and feet) at day 140. Secondary endpoints included time to repigmentation, F-VASI (Facial Vitiligo Area Scoring Index) at day 140, T-VASI/F-VASI50 at day 308, quality of life, and safety. The study consisted of 2 groups (A and B) with 100 participants each. Group A had afamelanotide implant treatment every 21 days with NB-UVB twice a week for 20 weeks. Group B only had NB-UVB treatment twice a week for 20 weeks. After the 20 week period, both groups were followed up 24 weeks later.
Dr. Kamangar shared clinical observations of the study through patient cases:
Figure I. Cutaneous examination of participant A showed repigmentation observed at day 21 and 80-90% repigmentation after day 140 with afamelanotide and NB-UVB therapy.
Case Study I. Participant A was a 55-year-old female with Fitzpatrick skin type IV who was diagnosed with vitiligo in 2006. The patient had slowly progressive disease with no previous episodes of repigmentation and no family history of vitiligo. The patient was unresponsive to previous vitiligo treatments. The patient was started on afamelanotide every 3 weeks and NB-UVB twice a week for 20 weeks. On physical examination, there was onset of skin repigmentation observed at day 21. Additionally, 80-90% of total repigmentation was seen after day 140 (Figure I).
Figure II. Cutaneous examination of participant B showed onset of repigmentation of the head and neck at day 30 and complete repigmentation of the face at day 140 with afamelanotide and NB-UVB treatment.
Case Study II. Participant B was a 52-year-old male with skin type IV who was diagnosed with vitiligo in 2023. The patient had progressive disease activity with no previous episodes of repigmentation and no family history of vitiligo. The patient had no history of previous vitiligo treatments. The patient was started on afamelanotide every 3 weeks and NB-UVB twice a week for 20 weeks. On physical examination, there was onset of repigmentation of the head and neck at day 30 and on the hands at day 42. One month after completion of the 20-week treatment course, the patient’s face achieved complete repigmentation. (Figure II).
Figure III. Cutaneous examination of participant C showed onset of repigmentation by day 42 and considerable repigmentation by day 106 with afamelanotide and NB-UVB treatment.
Case Study III. Participant C was a 56-year-old male with Fitzpatrick skin type IV who was diagnosed with vitiligo in 1999. The patient was started on afamelanotide every 3 weeks and NB-UVB twice a week for 20 weeks. On cutaneous examination, there was onset of repigmentation by day 42 and considerable repigmentation by day 106. The patient continued to exhibit repigmentation after conclusion of treatment protocol with no further therapy (Figure III).
Figure IV. Cutaneous repigmentation of participant D showed onset of repigmentation at day 30 with afamelanotide and NB-UVB treatment.
Case Study IV. Participant D was a 56-year-old male with Fitzpatrick skin type IV who was diagnosed with vitiligo in 1986. The patient was started on afamelanotide every 3 weeks and NB-UVB twice a week for 20 weeks. On cutaneous examination, time to onset repigmentation was observed at day 30. Due to extensive depigmentation, the patient is yet to exhibit complete repigmentation (Figure IV).
Figure V. Cutaneous repigmentation of participant E showed onset of repigmentation at day 21 with afamelanotide and NB-UVB treatment.
Case Study V. Participant E was a 46 year old male with Fitzpatrick skin type V who was diagnosed with vitiligo in 2004. The patient had non-progressive disease with previous episodes of repigmentation following treatment and family history of vitiligo. The patient was started on afamelanotide every 3 weeks and NB-UVB twice a week for 20 weeks. On cutaneous examination, time to onset repigmentation was observed at day 21 (Figure V).
The study showed a systemic effect with afamelanotide use in patients. There was total body darkening of unaffected skin followed by visible repigmentation of vitiligo lesions. Patients were counseled to anticipate total body darkening. Time to onset of repigmentation was seen as early as day 21. Spontaneous repigmentation was seen months after treatment in some patients. Overall, there was positive feedback from patients and physicians regarding clinical benefit. Combination with NB-UVB therapy has led to faster and more effective repigmentation in comparison to NB-UVB alone. This study shows the promising potential for afamelanotide as a treatment for vitiligo.
References:
1. Lim, H. W., Grimes, P. E., Agbai, O., et al. (2015). Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: A randomized multicenter trial. JAMA Dermatology, 151(1), 42–50. https://doi.org/10.1001/jamadermatol.2014.1875
2. Grimes, P. E., Hamzavi, I., Lebwohl, M., Ortonne, J. P., & Lim, H. W. (2013). The efficacy of afamelanotide and narrowband UV-B phototherapy for repigmentation of vitiligo. JAMA Dermatology, 149(1), 68–73. https://doi.org/10.1001/2013.jamadermatol.386
3. Minder, E. I., Barman-Aksoezen, J., & Schneider-Yin, X. (2017). Pharmacokinetics and pharmacodynamics of afamelanotide and its clinical use in treating dermatologic disorders. Clinical Pharmacokinetics, 56(8), 815–823. https://doi.org/10.1007/s40262-016-0501-5
4. Wu, J., & Cotliar, R. (2021). Afamelanotide: An orphan drug with potential for broad dermatologic applications. Journal of Drugs in Dermatology, 20(3), 290–294. https://doi.org/10.36849/JDD.5526
Affiliations:
1. Michigan State University College of Human Medicine, Grand Rapids, MI
2. Sutter Health, Palo Alto Medical Foundation, Mountain View, CA
Conflicts of Interest:
All authors report no conflicts of interest.