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Tuesday, 13 July 2010 08:00

Clinuvel reports positive results in Phase III porphyria (EPP) clinical trial

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Clinuvel Pharmaceuticals Limited (ASX: CUV; XETRA-DAX: UR9; ADR: CLVLY) today announced that it obtained positive results in a study which investigated SCENESSE® (afamelanotide) as a systemic photoprotectant in a 12 month, multicenter, randomised, double-blind, placebo-controlled Phase III crossover study (CUV017) in erythropoietic protoporphyria (EPP). In one Australian and seven European centres, SCENESSE® was evaluated for its ability to provide preventative pharmaceutical therapy in EPP patients who are known to suffer from phototoxic reactions following exposure to sun and light (>400 nanometres wavelength). The independent members of a Data Safety and Monitoring Board have reviewed the study results and have confirmed the conclusions.

Results

Primary Efficacy Analyses

A total of 91 patients completed the 12-month study, in which an 11-point Likert scale and physician assessments through case report forms (CRF) were used to evaluate pain as a principal symptom of phototoxicity. The duration of daily (sun)light exposure was used to assess the willingness of patients to expose themselves during all seasons. Melanin density (reflecting changes in skin pigmentation, measured by spectrophotometry) and quality of life (Short Form 36 surveys) were also evaluated.

In an analysis of the total number of days (frequency distribution) on which patients experienced pain in the specific pain severity categories (severe, moderate, mild and none), a significant reduction of frequency was observed in patients on active drug [p=0.0023]. Characteristic to EPP, the majority of phototoxic reactions occurred during spring and summer.

In analysing the average pain severity experienced by the total number of patients, the assessment of all individual daily pain scores was significantly lower in patients receiving SCENESSE® compared to those receiving placebo [p=0.0017].

An additional evaluation of the pain scores in patients willing to modify behaviour by continuous exposure to daily (sun)light showed a positive trend toward a reduction in average pain score following active drug treatment [p=0.1654].

Secondary Efficacy Analyses

Clinically relevant daily exposure of longer than one hour per day symptom-free was recorded by the trial physicians (CRFs) at the end of each 60 day treatment. In assessing the duration of sunlight exposure per patient, there was significantly more sun exposure in patients receiving SCENESSE® [p<0.0001]. These analyses strongly indicate that patients receiving drug increased their confidence to engage in outdoor activity.

In assessing skin pigmentation (melanogenesis as function of the drug’s pharmacological activity), a distinct clinical effect was recorded following administration of active drug, and in both treatment arms absolute melanin levels rose in one group by 29.1% and in the other by 28.4%.

The quality of life (QoL) observations of clinicians did not reflect the patients’ response to treatment. Quality of life assessment over the entire 12-month study was determined to be inappropriate for this population. Since the majority of patients wished to continue use of the drug after the end of the studies, alternative and disease specific quality of life measurements are being employed in the ongoing studies.

SCENESSE® was well tolerated, none of the patients who completed the study requested the treatment to be discontinued and no serious adverse event was reported to be drug-related. Complete results will be presented at the 19th Congress of the European Association for Dermatology and Venereology in October 2010.

Regulatory relevance

The genetic disease EPP - also described as absolute light intolerance - is known to impact patients from childhood onwards as they learn to adapt behaviour when experiencing the skin effects following UV and sun exposure.

The results from this trial demonstrate for the first time that patients who are able to overcome their anxiety to expose themselves to sunlight receive beneficial photoprotection from SCENESSE® reducing or abrogating the severity and frequency of cutaneous symptoms.

The study also demonstrates that the lifelong conditioned behaviour of patients remains a challenge in a placebo-controlled trial in which patients are uncertain whether they receive active treatment or not. Despite this uncertainty, only nine patients did not manage to complete the entire trial.

Of further clinical relevance were the statements by all eight physicians leading the trial and declaring that the majority of patients had reported the ability to engage in outdoor activities which had not been possible prior to treatment. Significantly, these activities are not captured in current standard Quality of Life surveys.

The reported safety and efficacy data after 12-months of intermittent drug use support the regulatory criteria of clinical relevance and beneficial treatment effect for SCENESSE® as a first line therapy for EPP patients.

Commentary

Clinuvel’s Chief Scientific Officer, Dr Hank Agersborg said:

“Today’s results are meaningful in that for the first time a mathematically significant treatment difference has been demonstrated. It is essential that we meet this EMA and FDA standard for placebo-controlled trials. It can be supported however that under realistic conditions of use simulating and approximating daily existence and risk, patients will wish to challenge themselves to risky behaviour - in this case UV exposure - only when they are assured that they will receive active drug. This is of particular relevance in EPP where patients have literally been burnt in the past.

“I am extremely pleased by these results as they will assist us in making a case to regulatory agencies on the grounds of drug safety, efficacy and need for treatment.”

Clinuvel’s CEO, Dr Philippe Wolgen said:

“These long-awaited results have taken us closer to our ultimate commercial objectives in the interests of both the patients as well as investors.

“In learning from pharmaceutical cases around us, and relevant to Clinuvel’s drug development, I view the sequence of expected regulatory scrutiny of data generated as essential. In EPP we are treating an orphan disease for which no comparable therapy can be accessed, as such, the demonstration of both short- and long-term safety data, is the single-most important parameter in the regulatory review process.

“This statistical outcome on safety and treatment effect support in presenting efficacy data to the regulatory authorities, whereby it is relevant to our filing that no other group has ever conducted large-scale therapeutic trials in this disease or has attempted to measure the effects of light on skin. Our team can be pleased by successfully having broken new ground.”

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See attached PDF for announcement appendices.

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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Clinuvel is an Australian biopharmaceutical company focussed on developing its photoprotective drug, SCENESSE® (afamelanotide) for a range of UV-related skin disorders resulting from exposure of the skin to harmful UV radiation. Pharmaceutical research and development involves long lead times and significant risks. Therefore, while all reasonable efforts have been made by Clinuvel to ensure that there is a reasonable basis for all statements made in this document that relate to prospective events or developments (forward-looking statements), investors should note the following:

  • actual results may and often will differ materially from these forward-looking statements;
  • no assurances can be given by Clinuvel that any stated objectives, outcomes or timeframes in respect of its development programme for SCENESSE® can or will be achieved;
  • no assurances can be given by Clinuvel that, even if its development programme for SCENESSE® is successful, it will obtain regulatory approval for its pharmaceutical products or that such products, if approved for use, will be successful in the market place.

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