In 2010, Clinuvel announced that it would commence a clinical trial of a new drug for vitiligo. In late 2012 the first treatment results from this program were announced with follow up results release in September 2013. The company has received a large number of questions related to its next trial and has released this Q&A to help people understand the steps to be taken to develop SCENESSE® in vitiligo. We’ve included a number of links throughout this document, as well as on Clinuvel’s website, to help people understand the technical content in a user-friendly manner.
Who is Clinuvel and what is your drug SCENESSE®?
Clinuvel is an Australian biopharmaceutical company developing drugs for individuals with a range of dermatological conditions.
Clinuvel has focused primarily on a drug called SCENESSE® (afamelanotide 16mg implant) which is an injectable implant drug roughly the size of a grain of rice. The active ingredient in SCENESSE® is a peptide called afamelanotide. This is an analogue of a naturally occurring hormone called alpha-Melanocyte Stimulating Hormone (α-MSH). In nature, α-MSH is our body’s response to skin damage from ultraviolet (UV) light. α-MSH binds to receptors (specifically melanocortin 1 receptor or MC1R) in the skin on particular skin cells, melanocytes, which in turn activate our skin’s pigment, melanin. Melanin provides skin cells with color as well as a biological barrier to protect them from UV and light. The skin is visibly darkened when melanin production is activated by α-MSH.
Afamelanotide’s chemical structure differs slightly from natural α-MSH: it has been altered to increase the peptide’s half-life (increasing the length of time it can exist in the blood stream from seconds to minutes) and to increase its ability to bind to MC1R on the melanocyte. As a result, afamelanotide is able to mimic the effects of the natural occurring α-MSH, with a longer lasting effect and increased potency.
Clinuvel has refined afamelanotide’s formulation and chemical structure to reach the current drug formulation and product: a 16mg afamelanotide controlled release implant, SCENESSE®. SCENESSE® has been formulated to achieve the optimal dose for activating melanin production systemically, while minimising exposure to the drug and thus reducing possible side effects.
SCENESSE® is administered by physicians in the fatty tissue just above the hip. Approximately two days after administration, SCENESSE’s visible effect can be seen in most patients: the skin appears darker due to melanin being activated in skin. In some patients however, melanin does increase but is not visible. To date, nausea and headaches are the primary side effects reported in the first 48 hours following administration of the drug during clinical trials, however the drug has been safely tested in more than 800 individuals over more than a decade with no reports of serious drug related adverse effects.
For the past six years, SCENESSE® has been trialed for a number of UV and light related skin disorders (conditions called photodermatoses). The most advanced of these programs is for an indication called erythropoietic protoporphyria (EPP), a rare metabolic disorder which causes absolute light intolerance. SCENESSE® has been shown to reduce the number and severity of phototoxic reactions in late stage trials of the drug in individuals with EPP and in February 2012 SCENESSE® was filed for marketing authorisation to be granted by the European Medicines Agency for EPP. A confirmatory six month Phase III US EPP trial commenced in May 2012 and results are expected to be published before the end of 2013.
In August 2010, Clinuvel announced it would commence a new program for SCENESSE®, trialing the drug for the first time as a repigmentation therapy in individuals diagnosed with generalised vitiligo (previously known as ‘nonsegmental vitiligo’). A Phase IIa (‘proof of concept’) study was started in the US (CUV102). Treatment results from CUV102 were announced in December 2012 with five month follow on results announced in September 2013.
To read more about our work with vitiligo, log onto http://www.clinuvel.com/en/vitiligo
How do you understand SCENESSE® to work to repigment skin in vitiligo?
The mechanism leading to vitiligo is still poorly understood in the medical community. Recent research has highlighted deficient pigment producing cells in the skin of patients with vitiligo, possibly indicating the important role of α-MSH in the disorder.
SCENESSE®, which mimics the effects of the naturally occurring hormone α-MSH, is believed to help restore this deficient system, and thus provide efficient therapeutic repigmentation for patients. Clinuvel has created a video and published an in-depth technology note to help explain this process in greater depth. To view the video, log onto http://www.youtube.com/watch?v=cbdla6ALCKs, to view the technology update log onto http://www.clinuvel.com/en/scenesse/technology-updates/technology-update-iii.
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, tools to measure vitiligo or depigmentation.
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 has been assessed by following the patients up clinically for five months and monitoring if their vitiligo returns to repigmented or new areas of their skin.
What are the treatment results from the CUV102 study?
Progressive repigmentation seen in a ‘Group A’ patient in the CUV102 study. Images (in order) depict repigmentation after:
Day 0 (Baseline)
Day 35 (15 NB-UVB treatments/1 afamelanotide implant)
Day 66 (29 treatments/2 implants)
Day 171 (62 treatments/4 implants)
A full copy of the company’s treatment results announcement from December 2012 can be found on our website: SCENESSE® successful in Phase IIa vitiligo study.
A presentation, providing an overview of our program and the treatment results was also released in December 2012: 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 indicates the extent of depigmentation – measurement tools.
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.
What are the follow up results from the CUV102 study?
Follow up results from September 2013 can also be found on our website: Five month study follow up shows SCENESSE® combination treatment provided stable repigmentation in vitiligo patients
We recognise that one of the greatest clinical challenges for treating vitiligo is that depigmentation can recur following successful therapy. To determine what effect SCENESSE® would have longer term if treatment ceases, patients from the CUV102 study were followed up clinically (attending consults with doctors involved with the CUV102 study) to assess the stability of their repigmentation. A comparison was made between patients in Group A and Group B five months after they completed therapy. It was found that repigmentation of vitiliginous lesions in patients in Group A (those who had received SCENESSE®) was significantly higher, as assessed by the VASI score, at clinical consults 224, 280 and 336 days after they had commenced therapy compared to Group B (respectively p=0.025; 0.037; 0.032, CI 95%)..
Will Clinuvel run further trials in vitiligo? When will SCENESSE® be approved for use in vitiligo?
Preparations are underway for a Phase IIb study of SCENESSE® in Asia which the company expects to commence the process before the end of 2013. More information will be made available by the company once this trial is due to commence.
No further studies have been announced in Europe or the USA at present.
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. If you’d like to receive specific email updates on the vitiligo program, please email mail@clinuvel.com requesting to join the vitiligo email list.
