FDA Meeting Confirmed to Advance SCENESSE® in Vitiligo
CLINUVEL PHARMACEUTICALS LTD [ASX:CUV; XETRA-DAX: UR9; Nasdaq International Designation: CLVLY] today received confirmation that the US Food and Drug Administration (FDA) has designated 29 April to discuss and agree the North American development program for SCENESSE® (afamelanotide 16mg) for the pigment loss disorder vitiligo.1
PROPOSED STUDIES CUV104 AND CUV105 IN NORTH AMERICA
The proposed study design comprises the treatment of vitiligo with SCENESSE® in combination with narrowband UVB (NB-UVB). In North America the standard of care is NB-UVB administered twice or thrice per week for up to 18 months to initiate repigmentation in vitiligo. Other treatment modalities consist of corticosteroids, calcineurin inhibitors, vitamin D3 analogues and melanocyte transplantation. Further treatments under development are oral and systemic JAK-2 inhibitors to provoke repigmentation, although no pharmaceutical product is currently approved for vitiligo in the USA. Vitiligo clinical experts agree that the current treatment modalities are deemed insufficient to provide a homogenous and consistent repigmentation solution.
FDA REGULATORY PROCESS
Pending ongoing safety and efficacy in its vitiligo program, CLINUVEL seeks to fila a supplemental New Drug Application (sNDA) for SCENESSE®. A sNDA, referred to as an “efficacy supplement”, is required to add a new indication to the labelling of an approved drug in the USA, with the submission consisting of clinical data supporting the new indication and any additional studies which may be required to support the efficacy and safety in the new indication. SCENESSE® was approved by the FDA in October 2019 to increase pain-free light exposure in adult patients with the rare metabolic disorder erythropoietic protoporphyria (EPP).
Discussions during the Type C meeting will focus on study protocol design, endpoints (study objectives) and final development leading to market authorization. Previous discussions between CLINUVEL and the FDA, first held in 2011, focused on the requirements to advance SCENESSE® in combination with NB-UVB for the treatment of vitiligo while one more preclinical study was successfully conducted to simulate the combination treatment proposed in man. This combination study demonstrated no safety issues of significance and good tolerability.
The FDA meeting will be attended by various global vitiligo experts and CLINUVEL’s senior regulatory and clinical managers.
SCENESSE® – REPIGMENTATION IN VITILIGO (PIGMENT LOSS)
In clinical trials conducted by CLINUVEL (CUV102 and CUV103) the combination of SCENESSE® and NB-UVB treatment resulted in more rapid and extensive repigmentation compared to treatment with NB-UVB alone.2 In CUV102, a proof-of-concept study undertaken in the US, a significant recovery of pigmentation was observed in patients with darker skin complexion (Fitzpatrick skin types IV-VI). In CUV103, a proof-of-concept study in Singapore, a more pronounced clinically meaningful recurrence of pigmentation for total body and areas of the head and neck was observed. However, a finding was that Singaporean vitiligo patients were not always accepting of the transient darker pigmentation of the confluent skin following afamelanotide treatment.
Afamelanotide has proven to be well tolerated with its safety profile maintained over clinical trials and post-authorisation use.
“Our team has been waiting for this moment, since we first planned to gain US marketing authorisation for SCENESSE® in EPP. This was received in October 2019,” CLINUVEL’s Chief Scientific Officer, Dr Dennis Wright said.
“It was obvious that a positive scientific review of SCENESSE® would need to come from the FDA’s Division for Dermatology and Dental Products before we would be able to initiate the final stages of the American vitiligo program.”
“Our overall aim is to provide repigmentation in patients who are most affected by vitiligo, reduce the frequency of clinical visits required by the current NB-UVB standard treatment protocols and thus see a decrease of radiation exposure for these patients.”
Vitiligo is a skin disorder characterised by the appearance of white to off-white skin patches (depigmented lesions) in different parts of the body due to the loss of melanin (pigment) production by melanocytes, the skin cells responsible for skin pigmentation. In vitiligo, melanocytes appear to lose their function. Vitiligo can start at any anatomical site and at any age and its causes are unknown (idiopathic). It is hypothesised that both genetic and environmental factors contribute to cause an autoimmune response in this condition. Vitiligo often affects the face, chest and extremities and may gradually spread to the limbs and other body surfaces. Patients are most affected psychologically when exposed parts of the body show extensive loss of pigmentation. Although vitiligo is seen in all skin types (Fitzpatrick types I‐VI), the highest psychological and societal impact is reported in darker skin complexions.
1 SCENESSE® (afamelanotide 16mg) is approved in the European Union as an orphan medicinal product for the prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP). SCENESSE® is approved in the USA to increase pain free light exposure in adult EPP patients with a history of phototoxicity. Information on the product can be found on CLINUVEL’s website at www.clinuvel.com.
2 CLINUVEL has published a series of scientific communiques on program for vitiligo and the mechanism of action of SCENESSE®: Vitiligo Communique I, Vitiligo Communique II, Vitiligo Communique III.
Results from clinical trials of SCENESSE® and NB-UVB have been published in:
• Lim, H. W. et al. (2015). Afamelanotide and Narrowband UV-B Phototherapy for the Treatment of Vitiligo: A Randomized Multicenter Trial. JAMA Dermatology. 151(1), 42.
• Toh, J. J. H. et al. (2020). Afamelanotide Implants and Narrow-band Ultraviolet B Phototherapy for the Treatment of Nonsegmental Vitiligo in Asians. JAAD. ePub 24 January 2020.