Earlier today we announced that two health insurers in Switzerland had agreed to reimburse SCENESSE® (afamelanotide) for the rare disease erythropoietic protoporphyria (EPP). While this is an encouraging step forward for the program and for Swiss patients, I felt it appropriate to take a moment to discuss the important role that Switzerland has played, and continues to play, in our EPP program.
In 2006 Clinuvel announced that it would commence a new clinical trial program focused on an unknown disease in a small open label study. At the time I noted that our aim was to “provide a prophylactic treatment for [a] debilitating and incurable skin disorder”.
The theory behind the use of the drug in EPP was quite simple. EPP is a metabolic disorder which causes the accumulation of a phototoxic chemical compound, known as protoporphyrin IX or PPIX, in the skin. When PPIX is exposed to specific wavelengths of light within the visible spectrum, it causes a phototoxic reaction underneath the surface of the skin which most patients describe as progressive, painful, debilitating and, unusually, invisible – there are no physical signs on the skin that a reaction is taking place. To prevent reactions, patients need to protect their skin from these wavelengths of light which, for most, means leading a life sheltered from light sources and hiding in the dark.
It was widely known that melanin, the pigment in skin, acts as a barrier between skin cells and light, preventing light from penetrating the upper layer of the skin and providing protection. This process was well understood with invisible ultraviolet light, where those with darker skin types have much lower rates of skin cancer compared to those with fairer skin. With the commencement of our EPP program, however, we were about to confirm that melanin, activated by our drug SCENESSE®, also protects skin from visible light.
The first EPP patients received the drug under a Phase II protocol at Zurich’s Triemli Hospital. This open label study, using a 20mg slow release formulation, showed promising results early on. Clinical measurements and patient reports suggested that the drug increased melanin density and improved patients’ tolerance to artificial and natural (sun) light. (For those interested, this study, CUV010, and its results have been published in the New England Journal of Medicine and Photochemistry and Photobiology). Perhaps more importantly, however, we received the first of many reports that the drug was having a positive impact upon patients’ lives, enabling them to do things they never could before because they could expose their skin to sunlight.
Encouraged by the Phase II reports, we worked to map out a broader EPP program which would help fully determine whether the drug could provide a safe and effective prophylactic therapy for these patients. A 12 month placebo controlled multi-centre European and Australian Phase III study protocol with the 16mg SCENESSE® implant (CUV017) was agreed and the first regulatory approval – received from Switzerland’s Swissmedic – saw the trial commence ahead of schedule, with the first patients enrolled at the Triemli Hospital. Mid way through this study Swissmedic granted SCENESSE® an orphan drug designation for EPP, recognising the drug’s potential to assist these patients for whom there is no other therapy.
Having completed the CUV017 study early, an interim efficacy analysis was conducted on 14 Swiss patients, showing that – even in a small sample size – the drug was having an impact, reducing the maximum and total severity scores for phototoxic reactions when compared to placebo. The results also provided the first longer term data on the safety profile of the drug in EPP, with no serious adverse effects or safety concerns identified amongst the patients.
For our team, however, the most encouraging ‘result’ lay beyond the study: all 14 patients had taken the unique step of requesting ongoing use of the active drug for the following 12 months, a treatment made possible under so-called ‘compassionate use’ laws. Many of these patients have since been granted ongoing access to the drug under these laws, providing them with a greatly improved quality of life and providing the program with important data on the long term use of the drug. Indeed, some Swiss EPP patients have received more than six years of almost continuous treatment with SCENESSE®. The feedback is very positive on both its use and effect.
We look forward to being able to continue ongoing treatment of the Swiss EPP community and expanding access of the drug to those who may not have been eligible for compassionate use. This week’s news provides the team with great encouragement as to the safety and efficacy of the drug, but also with great satisfaction that we are finally reaching our goal of delivering a therapy for patients who need it most.
“brienzen rothorn” uploaded to flickr.com by Martin Abegglen (twicepix) on August 26, 2010 <http://www.flickr.com/photos/twicepix/5244209675/in/photostream/>