Clinuvel Drug Shows Efficacy in Vitiligo, But Some Asian Patients Wary
Executive Summary
Clinuvel's Scenesse has shown promise in treating vitiligo in a Phase II trial, but recruitment has been slow because some patients of Asian ethnicity are concerned about overall skin darkening.
A clinical trial of Clinuvel Pharmaceuticals Ltd.’s Scenesse (afamelanotide) in Asian patients with the skin disorder vitiligo has shown that the treatment was clinically effective in achieving repigmentation in combination with narrowband ultraviolet B (NB-UVB) therapy.
However, recruitment to the Phase II trial, which was conducted in Singapore, was unexpectedly slow. For the first time since the vitiligo development program for Scenesse started, there were problems finding patients willing to take part because the overall skin darkening that the therapy produces is seen as “culturally and socially unacceptable in certain Asian populations,” according to Clinuvel.
Professor Steven Thng, principal investigator at Singapore’s National Skin Centre, said: “Having worked for a large part of my career in treating the entire spectrum of dermatology patients, this is the first time we have observed how strong cultural aspects dominate patients’ perception of skin colour and repigmentation, even though they suffer from vitiligo.”
Scenesse is already approved for the prevention of phototoxicity in adults with erythropoietic protoporphyria, a rare disease that renders patients intolerable of light. The vitiligo indication has been under development since 2010.
The current standard of care in vitiligo is NB-UVB over 12-18 months, but the response rate is low and repigmentation is incomplete, so combination therapies are often used to enhance repigmentation, Clinuvel said. An open-label US Phase IIa study in 2012 showed that Scenesse with NB-UVB produced faster and deeper repigmentation than NB-UVB therapy alone.
The Singapore Phase II trial (CUV103), which began in 2014, included patients of Asian ethnic origin with darker skin complexion categorised as Fitzpatrick skin types IV to VI (including Chinese, Indian and Malay origin) who had 10% or more body surface area (BSA) affected by vitiligo and had not received NB-UVB treatment in the six weeks prior to the start of the trial.They were to receive total body irradiation with NB-UVB twice a week for seven months, together with with subcutaneous afamelanotide or placebo every 28 days for six months (six doses in total).
The aim was to test whether a month’s treatment regimen would produce follicular repigmentation through the induction of dermal stem cells, and whether six doses of Scenesse in combination with NB-UVB would lead to repigmentation as assessed at seven timepoints in comparison with baseline values.
"Patients expressed concerns at the overall temporary epidermal darkening activated by Scenesse in combination with NB-UVB" – Clinuvel
However, the company had trouble recruiting patients who would accept temporary overall (pandermal) skin darkening, and the study design was changed from a randomized control study to an open-label study.
Of the 21 patients who enrolled, three receiving Scenesse plus NB-UVB decided to withdraw, “mainly due to concerns with experiencing much darker constitutional skin following drug administration compared to baseline, despite this having been explained during the patient consent process,” Clinuvel said.
“During clinical consultation these patients expressed concerns at the overall temporary epidermal darkening activated by Scenesse in combination with NB-UVB as skin darkening is culturally and socially unacceptable in certain Asian populations.”
Study Results
The study results showed a statistically significant improvement (decrease in the VASI scores) from baseline (Day 0) to end of the treatment (Day 196) for the total body surface as well as individual body areas: head and neck (p<0.001) and hands, upper extremities, trunk and lower extremities (all p<0.05).
There were statistically significant decreases (improvement) in the VASI scores compared with baseline and at subsequent timepoints throughout the study for the total body surface, the head and neck, upper extremities and trunk, and the hands and lower extremities. No differences in VASI over time were seen for the feet, an area that is quite resistant to repigmentation, Clinuvel noted.
There were also no statistically significant changes in pigmentation between the end of the treatment and the follow-up visit (Day 280) (all p>0.05). “This finding suggests that repigmentation had remained stable for the three months following completion of the treatment.”
Describing the trial as “most fascinating,” Thng said that “since there had been no effective systemic repigmentation therapy, patients’ anxiety for overall darkening of the skin had never been communicated and was a real surprise to us. This new finding indicates that dark skin versus whiter skin in vitiligo patients in Singapore is regarded quite differently than in other parts of the world.”
He said that while the therapy might in future be widely used in patients with vitiligo, “it will need to be restricted specifically to those patients of Asian descent who do not suffer the psychological distress of overall temporary darkening caused by the hormonal treatment. As a clinician I am primarily looking at the extent of repigmentation achieved, patient burden from the treatment and ease of use of a new therapy. Scenesse seems to meet most of these criteria,” Thng added.
Dr Pearl Grimes, director of the Vitiligo & Pigmentation Institute of Southern California in Los Angeles, took a different view. “We are observing similar efficacy results following the use of afamelanotide as we have found from the CUV102 study conducted in 2011-2012 in North America,” Grimes said. “The cultural aspects dominating the behaviour of patients of colour in Asia is not a surprise to me, since skin colour is an important perceived determinant of social mobility and self-esteem.”
The company now plans to look at exactly how Scenesse might be labelled for use. “It is imaginable that patients who have lost more than 10% of body surface area pigmentation would be eligible to receive the treatment,” said Clinuvel’s director of clinical affairs, Emilie Rodenburger.
“Vice versa, it is obvious that a patient who has less than 2% body surface area loss of pigmentation may not opt to receive a systemic injection of afamelanotide, but perhaps would use a topical formulation,” Rodenburger observed. “Clearly, we are positioning ourselves at the forefront of vitiligo treatment and are developing a number of scientific tools to accompany the technological innovation we wish to introduce.”
From the editors of Scrip Regulatory Affairs.