Clinuvel Pharmaceuticals Limited announced the results of the interim analysis of its phase-III trial studying the photoprotective drug afamelanotide in patients with erythropoietic protoporphyria (EPP). The interim analysis shows clinical benefits to patients suffering from this debilitating disease.
EPP is a rare genetic and metabolic disease characterized by severe phototoxicity of the skin resulting in intolerable pain, blistering and swelling typically of the hands and face. Patients experience aggravated symptoms of the skin following sun exposure, most commonly in spring and summer. As part of interim analysis, the data from the first 14 Swiss patients to complete the 12 month study period were analyzed. These represent the first out of 101 EPP patients in Europe and Australia being treated with afamelanotide under the same treatment protocol, and the study is expected to be completed in the last quarter of 2009. The study's result was that the severity of phototoxicity, determined as a primary endpoint to the study, was assessed by measuring the pain experienced during episodes of phototoxicity using a standard visual analogue pain scale.
The maximum severity of phototoxic reactions was significantly reduced by afamelanotide treatment compared with placebo (p<0.001) and the total severity of phototoxic reactions was reduced during spring and summer by afamelanotide compared with placebo (p=0.028). Skin melanin density, determined as secondary endpoint to the study, increased following afamelanotide treatment and then declined during the placebo treatment period as expected. There was a significant difference in the change from baseline in melanin density (skin darkening) for afamelanotide compared to placebo for the first two treatment periods, during spring and summer (p=0.048).
No significant differences between the afamelanotide and placebo treated patients were seen for the number of phototoxic reactions experienced, the amount of sunlight exposure or the quality of life measurements. This may have been due to the small numbers of patients (n=14). Importantly, there were no afamelanotide-related serious adverse events or safety concerns identified during the study. An independent Data and Safety Monitoring Board has reviewed the data on the safety and efficacy of afamelanotide in this clinical setting and consider it appropriate, and of benefit, to continue the study to its conclusion. On completion of the study by the Swiss cohort of patients, all 14 patients requested continuation of the drug for photoprotection for the next 12 months. This compassionate use request was granted by SwissMedic, the Swiss regulatory agency.
CSO Dr Helmer Agersborg commented, "In 2008, three regulatory agencies, the FDA, the EMEA and Swissmedic granted Clinuvel Orphan Drug Designation for the treatment of phototoxicity in EPP patients. The results of this trial are very encouraging. While this was an interim analysis involving data from only 14 patients, it was pleasing to see that afamelanotide reduced the severity of phototoxicity. If these results are repeated in the full study analysis, afamelanotide will be of clinical benefit in the reduction of the symptoms of EPP."
CEO Dr Philippe Wolgen said, "We are most happy with these results, but safety remains the most important aspect we are looking at when evaluating afamelanotide as a new class of drug in preparation for marketing authorization in various markets. It is a very positive sign that all Swiss patients requested further medication after completion of the trial. Today's results bode well, although we remain cautious in our predictions until the completion of the trials. We are on schedule in our development of afamelanotide and look modestly but confidently ahead to late 2009, when we anticipate the final Phase III results."
Afamelanotide stimulates the body's natural ability to produce eumelanin, the dark pigment of the skin which is known to have photoprotective properties, thus providing skin protection against UV radiation (UVR).
Clinuvel Pharmaceuticals Limited is an Australian biopharmaceutical company with offices in San Francisco and Zürich developing its photoprotective drug afamelanotide as a preventative treatment for a range of UV-related skin disorders as well as cancer related treatments.