Those who have taken an interest in Clinuvel will have learned with joy that, on Monday February 6th, the company announced its first official filing for SCENESSE® (afamelanotide) with the European Medicines Agency. It has taken our teams around six years to arrive at this point. Benchmarked against peer companies, it is a relatively swift development path for a first-in-class drug; we first publicly announced our erythropoietic protoporphyria (EPP) program in September 2006. It is an opportune moment to reflect briefly on how we reached this milestone and then discuss the steps that must be taken from here.
Clinuvel announced its first encouraging results from the EPP program in February 2007, following the completion of an open-label Phase II study (CUV010) of five patients in Switzerland. These results, published in the New England Journal of Medicine and Photochemistry and Photobiology, confirmed what had already been reported to the physicians involved throughout the study: afamelanotide enabled patients to expose parts of their skin to sunlight and monochromatic light – for the first time – without incurring phototoxic reactions. These reactions can range from swelling and burns to long lasting lesions, accompanied by intense pain for which no analgesic seems to work. These patients have been literally scarred for life.
These first results gave reason for optimism for the second larger trial, CUV017. In this multicenter trial, conducted in Europe and Australia, the physicians in charge learned that patients received a clinical benefit from the drug enabling them to lead an unrestricted outdoor life during the spring and summer. This was the first breakthrough in EPP we had seen under conditions of use. The drug’s reported safety profile was excellent, and with dialogue and guidance from the EMA, two new trials were initiated. The challenge for these studies was to capture data relevant to quality of life and outdoors exposure. In November and December 2011, we reported the positive outcomes of these studies – Phase II US (CUV030) and Phase III EU (CUV029) – which formed the final elements of the EMA submission. Being aware that regulatory agencies wish to see mid and long term safety data and clinically meaningful results, the other indications for which SCENESSE® was tested by Clinuvel have been included in our submission, providing essential supporting data from approximately 650 patients treated with SCENESSE®. Foremost, the results of all four EPP studies demonstrated SCENSSE® was a viable prophylactic treatment for EPP, and one which was well tolerated by those patients during the clinical program.
Running parallel to the clinical program, afamelanotide obtained orphan drug designations from the FDA, EMA and Swissmedic in 2008, and Australia’s TGA in 2010 for the treatment of EPP. This formal regulatory status entitles the company to certain incentives for its program. More than 20 individual regulatory approvals and consent from ethics committees for each trial site helped us to better understand the regulatory needs and ensured we conformed to the expected international standards. I expect there are many who follow the company and who don’t quite understand and appreciate the effort required to secure these approvals, but each one was a significant step toward our final goal and cause for confidence and celebration for our teams.
In May 2010 we received one of the biggest boosts to the program’s standing and further proof that we were on track to deliver this drug for patients for whom there is no therapy. At the completion of our first European Phase III study, the Italian regulatory authorities made SCENESSE® available for prescription prior to its formal EU approval, resulting in the company obtaining its first reimbursement for drug supply, known formally as an AIFA 648/96 listing. While maintaining our focus and yet with reasonable modesty, it indicated an important positive review in Europe. To our knowledge this special dispensation had never been given for a novel medical therapy in dermatology. Today, the Italian patients continue to benefit from SCENESSE®; their anecdotes of life on drug are most gratifying and make us realise how difficult life must be for those condemned to an indoors existence.
Over the course of the EPP program we collected more than half a million data points from patients, recording their experiences which differentiated between active and placebo treatment. More than a million physician report forms were written up and reviewed by the clinical study investigators and their teams. Without the dedication of the academic centers and their willingness to participate in the trials, we would not have reached our first filing. From this position, I thank both physicians and patients for their continued effort, time and belief in the drug and our teams.
Moving forward from the positive news and landmark event of submitting a first dossier to the EMA, new challenges lie ahead. The regulatory review period is an active process which will require more work and time from our teams over the coming months. The EMA’s task is to challenge our dossier and pose questions on all aspects of the drug’s development. Those who are familiar with drug development know that this process will take time, but we are confident that we have optimised the European dossier in anticipation of a rigorous review. Audits, inspections and reviews have been conducted and passed, but undoubtedly more will follow. Although the EMA review process is confidential, we hope to be able to give updates when appropriate. Looking further afield, we now await feedback from the FDA on the direction of our US program; another step which is entirely dictated by the FDA review and timelines and which will likely set new challenges for Clinuvel’s EPP program in 2012.
If there is one learning that I take away from the past six years, it’s that the CUV team embraces the numerous challenges along the journey and will continue to meet them. Health, persistence from our teams and safety of SCENESSE® are the requisites for further success.