We’ve just released the first results from our vitiligo program which you can view online here. Following their release, we expect a number of questions from the vitiligo community, some of which we hope to address below. If you have any other questions, feel free to contact us via Facebook or email.

What was the CUV102 study?

CUV102 was an open-label Phase IIa study conducted in three US expert centres (The Vitiligo & Pigmentation Institute of Southern California in Los Angeles, The Henry Ford Hospital in Detroit and Mount Sinai Hospital in New York). The trial was designed as a ‘proof-of-concept’: to explore the potential of SCENESSE® to repigment depigmented skin in vitiligo. In total, 54 patients enrolled in the study and 41 completed the full treatment course. All of these patients were of Fitzpatrick skin types III-VI, generally darker skin types.

All patients received narrowband UVB (NB-UVB) light therapy 2-3 times a week over a course of six months. Half of the patients (‘Group A’) in the study were also given four doses of SCENESSE®, one each at the start of months 2-5. The other half (‘Group B’) received only NB-UVB. Patients had their vitiligo monitored throughout the study using the VASI and VETF techniques, clinical measuring tools which have been developed specifically for vitiligo.

Results from these patients were then evaluated, comparing the results from Group A to Group B, to determine what effect, if any, the drug had on repigmentation. Specifically we wanted to know the effect of the drug on the speed of repigmentation after administration and depth (degree) of repigmentation achieved. Safety is a key issue in any drug trial, and was considered another key evaluation point. Finally, the overall stability of pigmentation is being assessed by following the patients up for six months and monitoring if their vitiligo returns to repigmented or new areas of their skin.

What are the results from the CUV102 study?

A full copy of the company’s results announcement can be found on our website: SCENESSE® successful in Phase IIa vitiligo study

We’ve also released a presentation, providing an overview of our program and results: Presentation: Clinical Study Results – US Phase IIa Vitiligo Study CUV102

Clinical trial results are based on the concept of statistical significance – how probable is it that the results are true or the result of chance? For those unfamiliar with reading trial results, we suggest first reviewing this post on our blog: Understanding clinical trial results – P values.

Using both the VASI and VETF methods, the study showed that patients from Group A (who had received SCENESSE® alongside NB-UVB) had favourable treatment outcomes compared to those in Group B (NB-UVB alone) at the completion of six months of treatment. These results were statistically significant for both the VASI – (p=0.025) which expresses total depigmentation – and VETF – (p=0.023) which expresses the extent of depigmentation – systems.

VASI can also be used to measure the time taken to see the first repigmentation in a clinical trial. Based on analysis of VASI scores in CUV102, those patients who had received the combination therapy achieved earlier repigmentation than those on monotherapy (a median time of 43 days versus 68 days p=0.086).

Analysis of a subset of darker skinned patients showed that patients in Group A showed significantly better, more complete and deeper repigmentation than those in Group B (p=0.046).

As an overview, based on results seen to date, we believe that SCENESSE® as an adjunctive therapy with NB-UVB phototherapy speeds up and assists the repigmentation process initiated by phototherapy, thus reducing the required dose of NB-UVB radiation. The extent and speed of this repigmentation varied, however, between patients and only a relatively small number of patients were involved in this study. Because of this, further studies are required in a larger number of patients to fully determine whether SCENESSE® is a safe and effective treatment for vitiligo.

Will Clinuvel run further trials in vitiligo? When will SCENESSE® be approved for use in vitiligo?

Based on the results of the CUV102 study, Clinuvel does expect to expand its vitiligo program in 2013, however the company is yet to announce when and where these studies will take place.

If there are more trials how can I participate? Can I register with Clinuvel?

Every clinical trial has inclusion and exclusion criteria which dictate which individuals can participate in a clinical trial. These criteria are determined by the company and/or physicians running the trial and approved by regulatory and ethical authorities.

Clinuvel does not recruit trial participants directly, as to do so may jeopardise the integrity of data generated in clinical trials. The company cannot respond to individual requests to be involved in the studies of SCENESSE® in vitiligo.

Clinuvel advises individuals with vitiligo to talk to their treating physician as they are best positioned to discuss the different treatment options for vitiligo, including clinical trials.

Is SCENESSE® available for purchase anywhere in the world?

Currently SCENESSE® is only available by a physician’s prescription in Italy and Switzerland under specific special access schemes. These schemes allow physicians to prescribe SCENESSE® to Italian or Swiss residents diagnosed with erythropoietic protoporphyria (EPP) but not for vitiligo. For more information on this scheme, see Clinuvel’s website.

SCENESSE® cannot be obtained outside of Clinuvel’s clinical trials anywhere else in the world.

When will SCENESSE® be available for vitiligo anywhere in the world?

This is a difficult question to answer at present as there are many variables involved in drug development. A ‘best case’ scenario would be 2-3 years, however this relies on future studies proving the drug to be safe and effective in a large number of vitiligo patients. The best way to stay abreast of updates is through our website, http://www.clinuvel.com.

How can I find out more about Clinuvel’s program for vitiligo with SCENESSE®?

Log onto http://www.clinuvel.com/en/vitiligo

Clinuvel Non-Executive Director Brenda Shanahan has been honoured at The Australian Financial Review and Westpac Group Woman of Influence 2012 Awards, being recognised as the second most influential woman in the category of Boards and Management from a field of over 350 nominees.

Mrs Shanahan has been a Director of Clinuvel since 2007, serving as Non-Executive Chair from late 2007 until July 2010. In addition to her role at Clinuvel Mrs. Shanahan is the Chair of the St Vincent’s Institute, an independent medical research institute in Melbourne, as well as a Non-Executive Director of Challenger Limited (ASX: CGF), Bell Financial Group (ASX: BFG) and DMP Asset Management. You can read Mrs. Shanahan’s full biography on Clinuvel’s website and more about the Women of Influence 2012 Awards at The Financial Review.

Since we publicly announced our vitiligo program in 2010, the entire Clinuvel team has aimed to gain a better understand this disease, its possible causes and how SCENESSE® (afamelanotide) may become a vital tool in a dermatologist’s arsenal for vitiligo.

We’ve also worked closely with the broader vitiligo community to better communicate the program’s goals and limitations (if you missed them, you can see the first two videos in a series of interviews between Mr Lee Thomas and our CEO here) as well as reaching out to individuals with vitiligo to better understand how this disease impacts upon lives. For me, one of the most prominent recurring topics in discussions, emails, phone calls and online is the lack of treatment for vitiligo and the frustrations of physicians and patients alike at treatment inconsistency.

Vitiligo is an insidious disease. While it causes no physical harm, the manner in which individuals lose their skin pigmentation can play constantly on their minds. Imagine waking every morning, expecting to see a slightly altered face in the mirror or different hands at your keyboard, feeling as if your identity was constantly under siege. This change in visual identity can lead to serious mental health issues and being ostracised from society or the breakdown of marriages. Compounding this further, stress itself can be a ‘trigger’ for vitiligo – one of many factors which has been linked to the onset of further pigment loss.

Unfortunately, we don’t understand the exact cause of vitiligo. While one can quickly dismiss myths about the disease, both genetic and autoimmune factors are suspected of playing some role. Current understanding suggests that an over active immune system within individuals with vitiligo attacks melanocytes in their skin, causing melanocyte cells to die and subsequent depigmentation. Without an exact cause in vitiligo, however, it is difficult to identify how it may be treated.

The frontline treatments for the disease take a two step approach: firstly aiming to halt the immune system from attacking melanocytes and causing depigmentation to spread, and secondly repigmenting skin via either melanocyte transplant or melanocyte stem cell (‘melanoblast’) stimulation. Some treatments aim to achieve both. Narrowband ultraviolet B (NB-UVB), for example, is known to suppress the immune system locally as well as penetrating to the depth of the hair follicle in skin to activate melanoblast migration. Unfortunately, however, treatments take a long time (NB-UVB, for example, is often administered 2-3 times every week for several years) and are notoriously inconsistent: not every patient will experience repigmentation, nor will it be universal. Even in those cases where repigmentation is seen, treatments often only halt the depigmentation process for a limited period of time before the vitiligo is triggered once more.

Over the past two years I’ve spoken with a large number of patients and families living with vitiligo from all over the world. I’ve also had the opportunity to hear from a number of world-leading vitiligo treatment specialists, both in conference situations and private conversation. In so many instances, due to their own lived experiences, the responses to our approach are the same: most are curious about our program, but approach it with cautious optimism.

This has prompted two responses from Clinuvel, to ensure we can properly evaluate the drug in our pilot study and to keep the vitiligo community abreast of our progress. The first is from our clinical team: following the completion of treatment in the current studies (CUV101 in Europe and CUV102 in the USA), patients will undergo a six month dermatological follow up to determine their levels of repigmentation and any possible disease recurrence. The second comes from a communications perspective: the team has sought to identify and converse with as many members of the vitiligo community as is possible, both 1-1 and through our various online and social media outlets.

Our vitiligo program has some way to come before we are satisfied that the drug is a safe and effective treatment and could present a package of data to satisfy the strict regulatory demand. Despite this, the company will continue to integrate itself as appropriately as it can to helping the vitiligo community and discussing our drug and program.

- Lachlan

References

• Chan MF & Chua TL, (2012). “The effectiveness of therapeutic interventions on quality of life for vitiligo patients: A systematic review”. Int J Nursing Prac, 18:396-405.
• Linthorst Homan MW, et al (2009). “The burden of vitiligo: Patient characteristics associated with quality of life”. JAAD, 61:411-20.
• Ongenae K, et al (2005). “Psychosocial effects of vitiligo”. JEADV 20:1-8.

Image reference

Two images showing a patient’s elbow before treatment and following exposure to 108 narrowband UVB treatments over 29 months. Images courtesy of Pearl E Grimes MD.

A new article was published last week looking at a small pilot study of SCENESSE® (afamelanotide) in acne vulgaris. Before discussing this piece specifically, I think it is relevant to briefly review melanocortins and their receptors.

The active ingredient in SCENESSE®, afamelanotide, has been the focus of over 80 peer reviewed journals (as well as being mentioned in at least 100 more) since the initial formulatory work with the drug began in the 1980s. In the last two years alone the drug and its actual or theoretical application in the clinic have been presented at least 20 times at various global scientific forums. This growing library of resources reflects the enthusiasm of the medical community to put a new compound through its paces, both in vitro and in vivo.

While much of this activity has focused on trial results or observations – such as those presented at the American Academy of Dermatology meeting earlier this year – others have chosen to focus on the potential of the drug to address various disorders or diseases, chiefly in dermatology, but also in other medical fields.

Afamelanotide is from a family of molecules known as melanocortins, based on the naturally occurring hormone alpha-Melanocyte Stimulating Hormone, or alpha-MSH. Afamelanotide binds with a particular receptor – melanocortin 1 or MC1R – on the walls of melanocytes – pigment producing skin cells – which in turn stimulates melanin in the skin.

Research into the properties of natural alpha-MSH has shown it to have a range of functions beyond pigmentation, with the natural hormone binding to further melanocortin receptors (numbered 1-5) present on various cells across the human body. Taking a step further, the activation (with an agonist such as alpha-MSH) or blocking (with an antagonist) of melanocortin receptors across the body could unlock a vast array of therapeutic potential.

Closer to our work, melanin also plays a number of roles in human skin. At Clinuvel we focus on two of its primary and best understood functions: photoprotection and pigmentation.

With a basic understanding of the role that melanocortins and alpha-MSH play in the functioning of human skin, it’s easy to see why there has been so much academic focus on melanocortins – these receptors and their agonists and antagonists present a range of possibilities for modern medicine, much of which we’re yet to fully understand.

This brings us back to the undertaken pilot acne study.

Acne vulgaris (just acne to most of us) is one of the most common dermatological disorders, affecting nearly the entire population at some stage of their life, but most commonly during adolescence. Acne is largely caused by a blocking of pores in the skin, the accumulation of sebum and subsequent inflammation resulting in comedones, pimples. For most people, acne is a moderate nuisance, destined to ruin high school photos and first dates. For up to 14% of people, however, acne becomes a distressing battle with the skin which continues well into adulthood. For these patients, a range of over the counter and prescription medications exist, with oral steroids currently used as the golden standard to reduce severe acne.

According to a range of non-clinical studies, natural alpha-MSH is widely understood to have an anti-inflammatory and anti-oxidative effect when it binds with certain melanocortin receptors, including MC1R in skin. Thus, the scientific question was posed: would afamelanotide, an alpha-MSH analogue, exhibit the same properties as the natural hormone when given to patients with acne?

After administering the drug to three adult male patients and observing the progress of their acne over eight weeks the jury is still out, but the authors of the piece – a team from the University of Muenster in Germany – conclude that the drug warrants further investigation for this common disease.

For the moment, though, it makes little sense for Clinuvel to pursue an acne program. The reasons are numerous, but many are covered in my piece last week on effective drug development. The opportunity may arise to return to a larger study for acne with a melanocortin drug and, if so, it is certain that this early stage clinical work will have played a pivotal role in advancing dermatological therapies.

- Lachlan

Reference

Bohm M, Ehrchen J, Luger TA, (2012). “Beneficial effects of the melanocortin analogue Nle4-d-Phe7-α-MSH in acne vulgaris.” JEADV. ePub 27 July 2012.

Image reference

A cross section of skin with acne from http://www.clinuvel.com/en/skin-science/skin-conditions/common-skin-conditions/acne-vulgaris

Take ten years, half a billion dollars and countless man hours from some of the most highly trained, intelligent individuals on the globe. You still stand a 90% chance of failure, some of which is totally out of your control. This is the apparent reality of modern drug development.

With the odds so stacked against it, it’s little wonder that the drug development sector is one requiring constant evolution in rethinking how to survive. In addition to the ‘regular’ risks of drug development, turmoil in global markets since 2007 has seen risk adverse investors shun drug development and biotechnology stocks for blue chip companies which are perceived as safer. The pressure to perform has increased for those companies who continue to work in the space.

In short, it’s forced even greater creativity to ensure survival and prosperity.

Like many peer companies who have reached a late stage of drug development, Clinuvel’s path was unique and hardly comparable to other pharma companies. (Each company has its own challenges and they are seldom comparable to others within the same sector.) By 2006 SCENESSE® (afamelanotide), our lead drug, had captured the public’s imagination, but was only in its infancy from a regulatory perspective.

To reach the market, a new drug must be proven safe and effective in a specific medical ‘indication’ (you can read more about this process on the clinical trials section of our website). The drug product must also be manufactured to a certain standard, known in the industry as cGMP, or current Good Manufacturing Practice. These three criteria (safety, efficacy and quality) should be constantly under review by any development company in the knowledge that they are the yardsticks by which regulators will measure a program and, ultimately, determine whether a drug can be marketed.

For Clinuvel it became obvious that the mechanism of action of afamelanotide – activating melanin in skin – would best be suited for a number of specialities, dermatology, gastro-enterology and haematology. Less obvious in 2006 was whether the drug would prove safe and effective as a prophylactic or symptomatic treatment for the chosen indications.

Melanin has numerous properties within the skin, but one of our key understandings – and now fundamental to Clinuvel’s program – is its ability to protect skin from various wavelengths of light. Here, melanin acts as an umbrella over skin, reflecting and absorbing photons of light across the electromagnetic spectrum and preventing them from penetrating into the layers of skin where they can cause the most damage.

In all skin types, the penetration of invisible ultraviolet light (UV, particularly wavelengths of 280-400 nanometers) over time can cause damage. For fair skinned individuals in particular, excessive exposure of skin to UV over a period of time will lead to skin cancer.

It made sense for Clinuvel to pursue the potential for our drug to prevent skin cancer, but we needed to narrow the playing field to make drug development realistic and feasible for patients who needed the drug most. In ‘healthy’ individuals, skin cancer takes decades to develop. A trial program here would also take decades to develop (a Phase IIb alone would likely be 1,000s of patients over 10 years), so we focused on a subset of patients who we knew were more likely to incur skin cancer in a shorter period of time – immunosuppressed organ transplant recipient (OTR) patients. Even here, a multi-year chronic Phase II study is being conducted, so proving the drug may help safely prevent skin cancer is still some way off.

Delving deeper, the company learnt more about less common disorders which are caused when sun/light impacts upon skin. Many of these – known broadly as photodermatoses – are acute diseases: symptoms occur within seconds or minutes of sunlight exposure. Consulting and in dialogue with experts who lead the field of photodermatology, we identified a small number of these diseases and set about the rigorous task of clinical evaluation of the drug’s safety and efficacy.

Since 2006 it has become clear that one indication is the most promising for SCENESSE®: erythropoietic protoporphyria or EPP. Here, melanin is blocking visible wavelengths of light (particularly blue light), preventing them from penetrating the skin and causing the painful phototoxic reactions which are characteristic of EPP. In practical terms, we are seeing that the drug is safely enabling EPP’ers to venture outside in sunlight for the first time. For many it is literally life changing.

Regulatory support for the EPP program in the form of orphan drug designations, along with encouraging patient and clinical evidence of the drug’s effect, compelled the team to accelerate this program. It was evident from our conversations with external parties, and clinical trial results, that EPP was the indication with the best opportunity to prove SCENESSE® was a safe and effective treatment. More recent support from payors in Italy and Switzerland suggests that there is now a broader recognition of this opportunity to deliver a drug for EPP patients.

Our task is not over and there are still significant hurdles for the company to overcome. While now recognised in Europe, US and Japan, EPP has a lower profile on other parts of the world and the company is working to expand the understanding of this severe disorder. Vitiligo presents a new challenge – our first program dedicated to pigmentary disorders where the drug may be able to assist millions of patients is still in its infancy and will require further trials and fine tuning. The aforementioned OTR skin cancer program will also complete its first study this year, and may present us with a further avenue of development. It’s a fascinating time for us.

Drug development is full of uncertainty. One thing, however, is certain – the Clinuvel team will continue to evolve our program to maximise our chances of getting SCENESSE® to the patients who need it most.

- Lachlan

Image reference
“Medicine” posted to Flickr.com by Kevin (KB35) on October 19, 2007 <http://www.flickr.com/photos/kb35/1644550531/>

The last five years have brought much change in the global pharmaceutical industry. As one of thousands of firms working in the space, we’ve taken a novel approach to try and overcome the challenges such change has presented.

This approach has taken us close to achieving what few of these firms will – proving that a new drug is safe and effective in its treatment of a disease and getting the product approved by the regulatory authorities. Every day the team and I have learnt something new that has helped us in this quest.

Over the next few months – coming from a different perspective as head of communications – I will try to share some of this knowledge with you via the blog; looking at how and why we do what we do, and trying to address some of the most common questions the company encounters on a day to day basis. I welcome your thoughts and feedback, either through comments on the blog, via Facebook, or directly via email to mail@clinuvel.com

- Lachlan Hay, Head of Global Network and Communications, Clinuvel

Several recent stories have caught the industry’s attention and set media imaginations alight, but none moreso than last week’s record-breaking US$3B marketing settlement between pharma giant GlaxoSmithKline and the US government. In short, GSK plead guilty to withholding safety data and illegal marketing practices related to three drugs and agreed to pay US$1B in criminal fines and US$2B to resolve civil complaints with the federal and several state governments.

The Financial Times responded to the GSK news by branding the industry as ‘unethical’ and called for greater transparency and scrutiny; particularly of industry-doctor relationships (you can read the piece with a subscription here). For some time we’ve been publicly discussing the role of illegal marketing, highlighting around 12 months ago the then record US$2.3B settlement Pfizer paid for activities similar to GSK’s. The practice has continued to grab the media spotlight as companies scramble to respond to the drying up of product pipelines and the ongoing demands of shareholders for increasing returns in difficult markets.

It has been clear that dramatic reforms were needed in our sector, and that the marketing and distribution of drugs required novel eyes, a different approach. Within Clinuvel this topic has been one of much debate in recent years, and a review of the pharmaceutical axis – company, insurers, prescribing physicians, and patients – has taken place in the context of the specific therapeutic area in which our teams operate. In summary, the driving factors for successful development of SCENESSE® have been the patients first, and physicians second. Due to our specific fields of focus, namely dermatology and gastro-enterology (with regards erythropoietic protoporphyria, or EPP), and due to the nature of the disorder the demand for treatment has been very much driven by patients’ experiences following drug administration.

Since 2006 Clinuvel has been working with the EPP community, a unique group of individuals (Recently I discussed the development of this program and I encourage you to read this piece, if you haven’t already). Having met EPP patients around the world it has become obvious to me that this disorder poses a severe burden on the existence of these patients and their families.

In the world of unlimited communication and social media, it became apparent in 2007 that patients’ perceived benefits of SCENESSE® as a newly introduced treatment, as well as possible side effects, would be best reported by patients themselves. Therefore, the company openly took the position that patients’ demand would largely determine the company’s decision to continue clinical trials and distribution, or to discontinue the development. In our case a remarkable shift in the pharmaceutical axis took place from physicians to patients, whereby positive clinical experiences became widely known through media channels, social media and Twitter and became key to our clinical program. Responding to patients’ experiences, we altered clinical trial protocols, discussed the patients’ needs and tailored the therapy regimen to the future use of the product: year round photoprotection.

By working closely with insurers, patients and absorbing the physicians views on ‘medical need’ and best clinical utility, Clinuvel secured early on a dialogue whereby the patient ultimately – in the case of porphyria – strongly made their experiences known to us, sponsor of the clinical trials.

In this particular program, we needed to return to the core value of delivering drugs and new solutions for patients. It’s complex, time consuming, costly and – at times – an incredibly frustrating endeavor. Yet, if successful, it can also be a journey of great satisfaction for all involved.

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.

Image reference:

“brienzen rothorn” uploaded to flickr.com by Martin Abegglen (twicepix) on August 26, 2010 <http://www.flickr.com/photos/twicepix/5244209675/in/photostream/>

Those who have taken an interest in Clinuvel will have learned with joy that, on Monday February 6^th, 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.

Earlier this week we unveiled a major update to our online presence with the release of our new-look website and the launch of Mothers & Children, a new site focusing on the pediatric and parental skincare.

Over the past five years the team has worked to continuously improve our online resources, expand into social media and build our presence on our Youtube channel (generating over 100,000 views in the process). The new site, Mothers & Children, is a direct response to what we saw as a key gap in online skincare information: up-to-date, accurate and concise information on caring for and protecting young and maternal skin. This is a new space for us and we’re excited to be able to compliment our extensive Science of Skin resources with this site.

We’re not standing still online. You will notice further changes in the coming months as they emerge from internal development and testing as well as new content being developed across the site.

Let us know your thoughts about our new site via Twitter, Facebook or email.