Last week I gave a snapshot of the formal process undertaken by the European Medicines Agency (EMA) to review a Marketing Authorisation Application (MAA) dossier under the Centralised Procedure. While this provides some context, looking at historical review timelines provides some sense of how long a future application may take. This is far from an exact science, but given the queries we have received of late on approvals timelines, I felt it appropriate to provide some internal perspective.

The EMA’s timelines are confidential, with only set time points at which companies are allowed to publish information (CHMP meetings in particular). Once a drug has been approved by the EMA, however, the Agency issues a summary of the entire review process, known as an EPAR, or European Public Assessment Report. This document outlines the timeframes required by the EMA to perform the review, along with the names of the co-rapporteurs and a summary of the product in some depth, much of which likely reflects the dossier submitted, albeit in an abbreviated version. (The EPARs are published online by the EMA and are free to download.)

At present, there are 65 approved orphan drugs represented with EPARs on the EMA’s website. These exclude at least one recent approval (Novartis’ Jakavi), but represent approvals dating back to 2001. The numbers tell an interesting story.

For all orphan approvals, the mean procedure time from submission of an application to European Commission ratification was 502 days, with a median time of 471 days. For those drugs approved from 2007 until today (36 drugs), those numbers drop to 500 and 460. If one excludes those orphan drugs which have had negative CHMP opinions issued and then been approved on appeal (Gilead’s Cayston, Epicept’s Ceplene and Pharmaxis’ Bronchitol), the 2007 until today mean is 481 days and the median is 453 days.

This seems like quite a process, but probably of greater relevance is the time taken from the EMA’s acceptance of a MAA dossier until the announcement of a CHMP opinion; which is widely considered the EMA’s review process. Here, the average review time for all 65 EPARs is 387 days, with a median of 358 days. These numbers don’t change significantly for the 2007-present period, unless you exclude the three negative opinions, producing a mean of 377 days and a median of 365 days.

The fastest review was Novartis’ Glivec (Gleevec in the US), which took just 121 days from dossier acceptance to CHMP opinion, with the 20 fastest reviews of orphan drugs taking, on average, 248 days from dossier acceptance to CHMP opinion.

The slowest review was Pharmaxis’ Bronchitol, which took 841 days (after suffering a negative opinion setback), with the 20 slowest reviews taking, on average, 555 days. (Bronchitol was, however, not the slowest drug to go from submission to EC approval; that was seen by Shire’s Xagrid, approved in 966 days in 2004 under Exceptional circumstances, and taking 110 days from CHMP opinion-EC ratification).

In reality, the figures can tell only part of the story. Each orphan drug’s path to market is unique, relying on years of work by dedicated teams to ensure a product can be proven safe and effective as a treatment for patients who have often had little or no previous therapy. Despite this, I will try to add context to the EPAR data after it has been released by the EMA and will update some of the numbers above, should anything relevant arise. Looking further, I also hope to be able to publish relevant news on the EMA’s review of Clinuvel’s SCENESSE® (afamelanotide) as and when the Agency allows us.

- Lachlan

Image reference:

‘Map of New Europe’ posted to Flickr.com by Cea. <http://www.flickr.com/photos/centralasian/6713923007/> (See site for license details).

For many years we’ve taken an active interest in the time required by regulatory authorities globally to approve orphan drugs. Clearly this kind of activity is required for forecasting and planning, but it also helps in communications to give our broader audience a realistic idea of the timelines ahead and some of the hurdles we may face.

Predicting timelines in drug development is an imprecise business fraught – each case or drug needs to be indivudally assessed, there are no comparables – but it is nonetheless one method by which we can anticipate the period of time required before any decision from the European Medicines Agency (EMA) is published.

The EMA has a set process by which orphan drugs are evaluated. Following an orphan designation in Europe – the recognition that a drug may have the potential to treat a rare disease – the EMA will use the Centralised Procedure (CP) to review the drug’s marketing authorisation application (MAA). Under the CP, two ‘co-rapporteurs’ are appointed to review the complete dossier. These are individuals within two of the recognised national EMA authorities (such as ANSM in France, BfARM in Germany, MHRA in the UK and AIFA in Italy) who act as the central contact points for the EMA’s review.

These two individuals (or, more specifically, the agencies they represent) review the dossier in-depth and ask questions of a company along the way on behalf of all EMA agencies represented. The process then follows a set of formal steps, running to a 210 day ‘clock’ in a standard review:

1. Validation. Once a MAA dossier is submitted, the first step is to ‘validate’ all the documents in the dossier to ensure they are present and have been formatted according to the EMA’s requirements. This usually takes 1-2 months (but can take longer if there are serious errors or omissions).
2. Clock start and initial review. Following validation, the EMA gives the co-rapporteurs 120 days to perform and initial review of the dossier. After 80 days, an Assessment Report is submitted to the sponsor, with a list of unofficial questions which have already been raised by the dossier. At day 120 the co-rapporteurs submit an official list of questions to the sponsor, raising key issues within the dossier, including any found during inspections of manufacturing, non-clinical and clinical study sites.
3. Clock stop and up to six month response time. At day 120 the official clock is ‘stopped’ and the sponsor is given three months to respond to all questions submitted by the co-rapporteurs. A further three months can be given..
4. Clock start and 60 day review. Once the sponsor has responded, the clock restarts (day 121) and the EMA has a further 60 days to review the response and raise any outstanding issues.
5. Clock stop at day 180 and up to three month response time. At day 180 the clock is stopped again when the EMA raises further questions. At this point the EMA can also request an oral explanation of the sponsor – to present before a panel of regulatory authorities and medical experts and discuss the MAA dossier. The sponsor is given up to 3 months to prepare their response (whether in writing or for an Oral Explanation meeting).
6. Clock start and preparation of CHMP opinion. When the response is delivered by the sponsor, the clock starts again at day 181 and the EMA’s Committee for Medicinal Products for Human Use (CHMP) is given 30 days to prepare a final opinion on the product’s dossier; the final hurdle to EMA approval. The CHMP can issue one of three opinions: approval, conditional approval and rejection (a negative opinion). An approval may also occur with ‘Exceptional circumstances’ – a situation where data may not prove that a drug is safe and effective beyond all doubt, but recognises that this may not be possible and places further obligations on a sponsor following an approval (16 of the 65 orphan drugs approved by the EMA¹ have been approved with Exceptional circumstances).

One final step exists, however, once the CHMP approves a drug, which is to forward the opinion in all languages of the European Union to the European Commission to adopt the drug under relevant laws, finally allowing its marketing across Europe. For orphan drugs this final step can take as little as 48 days, but the reported average is about 88 days.

Next week I’ll look at some of the orphan drug approval statistics in greater depth to gain a sense of how long the approval process for SCENESSE® (afamelanotide) may take.

- Lachlan

¹ Refers to the 65 orphan drug European Public Assessment Reports (EPARs) available at time of writing for orphan drugs on the EMA’s website. Jakavi, a recently approved drug, is at the moment excluded from these numbers. I’ll explain this analysis process in greater depth next week.

- Lachlan

Image reference:

“Skyline Brussel bij zonsondergang” posted to Flickr.com by Erasmushogeschool Brussels on January 7, 2009 <http://www.flickr.com/photos/erasmushogeschool/3179373114/>

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.

“Basal cell carcinoma skin cancer is the most common form of skin cancer”. It’s a common claim and one which is undoubtedly true – non-melanoma skin cancers (or NMSCs) are seen far more frequently than any other form of cancer. Unfortunately, however, due to their frequency, statistics on the incidence of NMSCs (which include basal cell carcinomas, BCCs, and squamous cell carcinomas, SCCs, of the skin) are difficult to find and cross-reference.

Recognising this gap, a research group from the University of Nottingham established a literature review to try and establish what comparable published data could be found to determine the incidence of NMSCs. Whittling down some 3083 publications, the group identified 75 papers which provided suitable information, covering 38 countries from 1955-2007.

While you can review all of the group’s findings online (along with acknowledged possible issues with data), a few key findings are worthwhile highlighting:

• UK rates of BCC (when standardized for age) are 89 cases per 100,000 persons between 1996 and 2003, with higher rates in Scotland (97.5 cases per 100,000 persons).
• Pan European rates of BCC have been increasing at around 5.5% per year for the past 40 years, with the highest rates in Switzerland and Italy.
• Australia has the highest incidence of BCC in the world, with 884 cases per 100,000 persons in 2002; a rate which “appears to be reaching a plateau” after increasing since 1985
• SCC rates are markedly lower than BCC, but have been on the rise in most regions.

Echoing calls from the UK’s National Institute for Health and Clinical Excellence (NICE) (which issued guidance on NMSCs and other skin cancers in 2010), the authors conclude by highlighting the potential burden NMSCs may pose in future. A better understanding of the incidence of these cancers will certainly help in planning their prevention and treatment.

Reference

Lomas, A, Leonardi-Bee, J & Bath-Hextall, F (2012). “A systematic review of worldwide incidence of nonmelanoma skin cancer.” British Journal of Dermatology 166:1069-1080. Available online.

Image reference

“Wollaton Park Sunset” posted to Flickr.com by Duncan Harris (Duncan~) on February 5, 2012 < http://www.flickr.com/photos/duncanh1/4246379902/>

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/>

In a letter published this week in the British Journal of Medicine three dermatologists have highlighted the potential risks posed by the Royal Mint’s new 5 and 10 pence coins to those with certain contact allergies and called on the government to review the new tender.

Earlier this year the UK’s Royal Mint began using a cheaper metal for the coins (nickel coated steel instead of cupronickel, an alloy of copper and nickel) to help offset the rising cost of production. This new coin, the dermatologists contend, may pose a greater risk to those with eczema and nickel allergies and they’ve asked the UK Government’s Chief Scientific Adviser, Sir John Beddington, to review the situation. The authors note that the Swedish central bank, Riksbank, had recently concluded that nickel coated coins posed “unacceptable risks to health”.

According to The Telegraph newspaper, the changes were made to save the UK government £7-8million (US$11.2-12.9million) a year, yet the dermatologists contend that there has been no thought given to potential increases in costs from allergic reactions to Britain’s National Health Service (NHS). Nickel allergy is considered to be one of the most common causes of contact allergies, leading to symptoms of atopic dermatitis, or eczema.

The Mint, which issued 1.1 billion coins in 2010-11, is yet to issue a public statement on the issue but told the Financial Times that it “adhered to all the relevant legislation and guidelines relating to the introduction of new coinage and can confirm that the new nickel-plated 5p and 10p coins have no additional potential to cause adverse effects on people with allergic contact dermatitis and hand dermatitis”.

Image reference

‘five pence’ uploaded to Flickr.com by johninbkk on May 24, 2008 <http://www.flickr.com/photos/jinbkk/2518583086/>

In the final post from the Roosenboom family, and to help recognise Rare Diseases Day, Simone has penned her own piece on her experiences with Hydroa Vacciniforme. We are grateful to the Roosenboom family for being able to share their story.

Hi, all.

My name is Simone and I’m almost fifteen years old. I got ill when I was nearly six; exactly nine years prior to the day I wrote this. You can read all about that in the previous blogs written by my father.

The first years, my illness troubled me, but it got worse when I turned ten years old. The year 2007 turned out to be a horrific year for me. I got a bit older and more aware of myself and the way my surroundings reacted to my appearance. I looked quite scarred and felt that I was different. Quite a lot of people acted in a way that strengthened that feeling: they looked at me with horror. My parents and I got quite upset with that, even to the point that my mother told these people in anger that I was contagious so they would quickly get away from us. I thought it was funny but in the end it didn’t change anything.

The situation at school got worse also. I was bullied, called names and treated like an outcast. They called me a zit and fatty because of my blisters and overweight. It made me sad and angry and I kept it all in. The bullying lasted several years: far too long for me to handle. Something in me broke. At age twelve, I was that angry that I considered it being better not to live than go on this way. I had really had it with the situation.

The last months of primary school I avoided school and went to a psychologist, but that didn’t solve much. Only when I went to middle school things turned to the good for me. I got a nice welcome and felt I could make a new start. People treated me normal and I made some nice friends, who still are there for me when I need them. Most of the bullying stopped, although sometimes there was a lack of understanding when for example gym class was held outside in warm and sunny weather and I had to stay indoors. If only they knew that I would have loved it! Nowadays I’m in third grade of middle school. Classmates sometimes asked me what disorder I was suffering from and what caused it. So I gave a lecture in class once. I meet a lot of understanding now, which feels really good.

Last summer I noticed that I was doing a bit better, I mean, parts of my body started to react less severely to UV-radiation. I even went to the beach the last day of the vacation, wearing protective clothes and sunscreen but not on my lower arms and –legs. That was so cool! And I had no blisters afterwards! After over eight years I felt the wind blowing softly along my legs. So simple, yet so special!

Image reference

Simone today, courtesy of the Roosenboom family

We recently invited Richard Roosenboom to share his experiences as a parent of a child with a rare disease. In the coming weeks we will publish part of the Roosenboom’s story in a four post series. In part one of this post Richard described the onset of Simone’s disorder and the road to the diagnosis Hydroa Vacciniforme (HV) some months later.

Our local hospital learned about Simone’s diagnosis with HV and invited us to discuss her condition. They felt that the diagnosis needed confirmation by tests. Yet, as HV itself cannot be confirmed by tests, that meant that Simone would have to undergo a series of examinations to exclude other diseases and disorders. They felt that the diagnosis of HV could be accepted only if all others had been excluded. We learned about some tests being quite painful and harmful to Simone’s skin and took control again: we refused. We decided to accept her having HV and not having her undergo such an ordeal, knowing that even if HV was confirmed, it would change nothing.

In the same period we said goodbye to our local dermatologist and a health care service for children, because we needed to explain the disorder to them in order to get good care for Simone. In the same timeframe Simone got sores in her mouth which were HV related. Our dentist was open to this explanation but, later on, her orthodontist believed that her teeth weren’t correctly brushed. Another lack of understanding to fight.

Things got quiet around Simone from September (2003) on. The whole journey from February to September had taken up so much of my wife’s and my own energy that we went on vacation for a week and a half to get some rest. We went to Sicily, Italy, without the children obviously: Simone could not enjoy the sun anymore! We were too tired to feel guilty about our trip. And although Sicily is a beautiful island with history and culture, we didn’t do anything but resting at the pool and enjoy some nice dinners.

Back home again, we turned our attention to Simone again. We bought some dense woven swimming suits from Australia via the internet. With these long sleeved and –legged suits Simone could enjoy staying outside up to two hours a day. We treated her face with SPF60 every hour, and had her playing under a parasol. A more effective sunscreen was offered to us, but it would cause Simone’s skin to turn pink. Because she so desperately wanted to be normal and accepted, we rejected using that as well. She also used a lip balm with SPF25 because her lips got affected by the radiation.

We tried to get some compensation for all our extra costs from our health insurance but that was rejected. Also compensation via a special sanitation law was denied. None of our treatment and preventative costs fell within the laws in place to reimburse patients in the Netherlands; an example of how rare diseases are systematically discriminated, largely due to ignorance, by institutions and law makers.

Sadly, when Simone was outdoors too long, some blisters would occur and she would suffer from nausea and headaches. Later on we learned that some kind of mild sunstroke also follows being exposed to the sun for too long. Slowly we all got used to the fact that spontaneity wasn’t meant for us anymore. We, the adults, could of course cope with that a lot better than our children. Yet, never again being able to do as you like takes its toll on everyday family life.

A major breakthrough was when my parents discovered an SPF90 sun screen, being on holiday in Spain some years later. This product was especially developed for use on skins intolerant to UV-A and –B radiation. Now Simone could stay out for up to four hours. To avoid headaches we still kept her in the shade.

At primary school, Simone was doing fine at first. When she and her classmates got older however, they accepted less and less of her. Simone stayed home sometimes, and couldn’t enjoy sporting days or daytrips. On one school camping trip I had to collect her on the first night – she just wasn’t able to cope. As time went by, she slowly became an outcast. Again Simone wouldn’t go to school. Fortunately the situation improved when she went to middle school some years ago and made some new friends. She is doing quite well now, to her and our relief.

Two years ago, after a tip from a neighbor (thanks Frank!), we learned about the Clinuvel company developing a medicine for EPP. While we know at present there are no trials for HV or for children, it was encouraging to know someone was working in the space of skin diseases caused by light and trying to find new ways to protect skin like Simone’s. Together we also arranged for HV to be described on the company’s website, adding to the broader awareness of the disease.

Also two years ago I launched a website for Simone and HV in the Netherlands. I wrote down her story and described what means we use for coping with HV every day. To my surprise, last year we were contacted by an HV patient and the mother of a young HV patient, both in the Netherlands. This was a very emotional moment for Simone since she always thought to be the only one with HV in our country of 16 million inhabitants.

Simone turns 15 next month. Next week she will have lived with HV for nine years. And yes, she seems to be healing spontaneously slowly since puberty, but only for some parts of her body. Her lower legs and arms seem to be more toleration of UV radiation. Encouraging, but we feel that there’s still a long way to go. Gladly, Simone is quite positive about it, and we should be too.

Editor’s note: You can read more about HV at http://hydroavacciniforme.nl/

Image reference

Simone in her protective sun gear courtesy of Richard Roosenboom.