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Thursday, 03 November 2011 20:56

Clinuvel demonstrates positive treatment effect of afamelanotide in US Phase II study

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Analyses from US confirmatory study demonstrate a dramatic improvement in Quality of Life from SCENESSE® (afamelanotide 16mg) in the ‘orphan’ disease erythropoietic protoporphyria (EPP)

Melbourne, Australia and Baar, Switzerland, November 3, 2011

Executive summary

  • EPP patients who received afamelanotide (active drug) were able to spend more time in direct sunlight between 10 AM and 3 PM and 10 AM and 8 PM (p=0.036, p=0.025).
  • Photoprovocation on the back and hand in a subset of patients showed a significant treatment effect up to Day 60 (p=0.019 to p=0.045, depending on the study day and body site tested).
  • Afamelanotide significantly improved patients’ Quality of Life (QoL) as measured by an EPP-specific QoL questionnaire at Day 180 (p<0.001) and at Days 60 and 120 (p=0.001 and p=0.003). The generic DLQI was insensitive to changes in quality of life in EPP (non-significant).
  • All treatment centres (6) reported positively on the trial and treatment effect and requested afamelanotide 16 mg for further use on behalf of their patients (FDA pending).
  • Data Monitoring and Safety Board (DSMB) reviewed the analyses and deemed the drug safe for further use on the basis of the adverse event profile seen in this and other studies.

Clinuvel Pharmaceuticals Limited (ASX: CUV; XETRA-DAX: UR9; ADR: CLVLY) today announced that analyses of its Phase II US study in EPP (CUV030) had shown a clinically relevant positive prophylactic treatment effect for patients who had been administered SCENESSE® (afamelanotide 16mg controlled-release formulation).

SCENESSE® is the first photoprotective drug developed as an orphan product for the prevention of symptomatic EPP. Clinuvel is currently finalising a Marketing Authorisation Application (MAA) for SCENESSE® for submission to the European Medicines Agency (EMA) before the end of 2011.

STUDY DESIGN

CUV030 was a randomised placebo-controlled trial consisting of two parallel treatment arms conducted in six different US academic centres which recruited a total of 77 EPP patients. The drug was tested during six months of spring and summer under conditions of use. Patients recruited were evenly distributed over all six university centres.

This study and its objectives were designed in conjunction with the European Medicines Agency (EMA) following advice through the Protocol Assistance (PA) program obtained in 2009 and global experts in porphyria management.

CHARACTERISATION OF DISEASE AND STUDY OBJECTIVES

EPP is reported as a serious and heavily disabling disease, whereby patients have learned to avoid (‘adapted behaviour’) the sun and UV exposure under ambient conditions to avert the emergence of phototoxic pain and burns. Characteristic of EPP patients - and different from other photodermatoses - is that they experience prodromal symptoms upon light and UV exposure, meaning that they are able to feel their dermal symptoms developing. This phenomenon causes them to escape daylight upon experiencing these first symptoms. Significantly, EPP patients are conditioned to avoid light and UV from childhood and through adapted behaviour have learned to live indoors and lead nocturnal existences.

The primary objective of evaluating afamelanotide in EPP patients was to determine whether the prophylactic effect has clinical benefit. The clinical relevance of the proposed treatment with afamelanotide is expected to allow patients to lead a life which includes exposing themselves to ambient light and to engage in outdoor activities. A similar, secondary objective was to assess the effect of treatment on the impact on Quality of Life (QoL).

RESULTS AND ENDPOINTS

Seventy-seven patients started the study and 68 completed study medication and all clinical visits. In total 12,254 days were evaluated during the six month study. An adaptive and compound statistical analysis was performed. Results of the study showed that SCENESSE® was well tolerated, allowed EPP patients to expose their skin to sunlight during the middle of the day and improved their Quality of Life (QoL). Overall the study demonstrated a strong clinical benefit to patients, despite their deeply learned behaviour to avoid reactions caused by sun exposure.

Overall, EPP patients who received afamelanotide (active drug) were able to spend more time in direct sunlight between 10 AM and 3 PM and 10 AM and 8 PM (p=0.036, p=0.025) in comparison to placebo patients. The indicated times are the periods of the highest UV intensity, equating to the ‘brightest’ times of the day when EPP patients are most at risk of developing symptoms. Patients on drug reported a three-fold increase in the median amount of time in direct sunlight compared to placebo. Consequently many patients on drug reported no pain or only mild pain compared to their previous life of experiencing severe phototoxic reactions.

A subset of patients was subjected to photoprovocation (laboratory testing) on the surface of the hand and lower back to assess the time and dose to provoke to minimal symptoms (MSD). Of 15 patients who started the testing, only six completed the four month provocation (40%). Although a positive trend was found in the first 60 days (p=0.019 to p=0.045), no statistical significant result was found for Days 90 or 120 when fewer patients were retested. The substantial reduction in participants was attributed to the rigors of the phototesting protocol.

In analysing the impact of drug on the Quality of Life (QoL), a positive difference was found between mean (average) scores recorded at baseline (before start of treatment) and at day 60 (p=0.001). A positive impact of treatment was also found between mean scores recorded at baseline and at day 120 (p=0.03) and day 180 (p<0.001). Similar results were not found when the more generic Dermatology Life Quality Index (DLQI) was used.

Most common adverse events were associated with implant administration (such as pain or bruising following injection) and transient nausea and headache. After reviewing and confirming all analyses and the safety data, the independent Data Safety Monitoring Board (DSMB) deemed afamelanotide safe for further use in man.

All study centres reported positively on the afamelanotide 16mg treatment and requested the drug on behalf of their patients for compassionate use. The FDA will decide whether Clinuvel should supply the drug after reviewing the analyses of this trial.

COMMENTS

Clinuvel’s Chief Scientific Officer, Dr Hank Agersborg, said: “I am very pleased by these results. EPP is a disorder requiring patients to adapt their lives by avoiding ambient light and conducting a life of isolation. It is the first time we observed and quantified how the drug changes behaviour and quality of life.”

Dr Robert J Desnick, Dean for Genetic and Genomic Medicine and Professor and Chairman Emeritus of the Department of Genetics and Genomic Sciences at Mount Sinai School of Medicine, New York, and a lead investigator on the CUV030 study commented: “The results clearly indicate that afamelanotide increased patient exposure to light without severe pain. Patient demand for ongoing treatment following the study indicates that there is a clinical benefit to the drug."

Dr Hank Agersborg concluded: “We are fully aware that in today’s regulatory climate meeting study objectives and endpoints in smaller populations of patients is as important as demonstrating treatment effect and clinical relevance of the new proposed drug to obtain marketing authorisation. We now await the final results from the European Phase III study. If similar findings emerge from this study, Clinuvel will have sufficient data to support a submission to the EMA for SCENESSE® as a first line therapy for EPP. This is meaningful for patients because it will allow them to undertake activities which were never possible before because of the risk and consequences of sun exposure. Clinuvel will now enter a discussion with the FDA to assess the final requirements for our US EPP program.”

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Investor relations contacts:

Australia: Clinuvel Pharmaceuticals Limited, T: +61 3 9660 4900
Europe: Clinuvel AG, T: +41 41 767 45 45
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Media contacts:

Lachlan Hay
Clinuvel AG
Baar, Switzerland
T: +41 41 767 45 45
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Nick Miles
Cabinet Privé de Conseils s.a.
Geneva, Switzerland
T: +41 22 321 4540
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Ted Agne
The Communications Strategy Group Inc.
Boston, Massachusetts, USA
+1781 631 31 17
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