Recently I’ve had the great pleasure of speaking with Lachlan Hay, Head of Global Network and Communications, Media Communications & IT Team @ Clinuvel. I had many questions about Scenesse®; how it works, the clinical trial process, and when it will be offered world-wide. Mr. Hay was kind enough to answer every question in detail.
Here is the interview:
Recently, the Australian company Clinuvel announced that it would commence a clinical trial of a new drug for vitiligo. The company has received a large number of questions related to its proposed trial and has released this Q&A to help people understand the potential, and potential limitations, of its program.
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) 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 (?-MSH). In nature, ?- MSH is our body’s response to skin damage from ultraviolet (UV) light. ?-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 ?-MSH.
Afamelanotide’s chemical structure differs slightly from natural ?-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 ?-MSH, with a longer lasting effect and increased potency.
Clinuvel has refined afamelanotide’s formulation and chemical structure to reach the current drug formulation: a 16mg afamelanotide controlled release implant, SCENESSE®. SCENESSE® has been formulated to achieve the optimal dose for activating melanin production systemically, while minimizing 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: the skin becomes darker. The drug is only present in the body for approximately ten days however the effect of the drug is seen for 60 days. Hence, in current clinical trials, SCENESSE® is administered once every 60 days. To date, nausea and headaches are the primary side effects reported in clinical trials however the drug has been safely tested in approximately 550 individuals with no reports
of serious adverse effects.
For the past five 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 a confirmatory program is underway in the US and Europe. Pending the outcome of this confirmatory program – due to complete in the first quarter of 2011 – Clinuvel expects to file SCENESSE® for Marketing Authorisation Approval (MAA) with European regulators.
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 nonsegmental vitiligo. The company is currently making submissions for regulatory and ethics approvals to commence a pilot Phase II study in four centers, two each in the US and Europe, which will evaluate SCENESSE’s ability to repigment skin both as a standalone therapy and as an adjunctive therapy with narrow-band ultraviolet B (NB-UVB) light therapy.
To read more about our work, log onto http://www.clinuvel.com
How do you expect SCENESSE® will work to repigment skin in vitiligo?
The mechanics the vitiligo are still poorly understood. Recent research studies have highlighted numerous ?-MSH and MC1R abnormalities in the blood and skin of patients with vitiligo, demonstrating the important role of ?-MSH in the disorder.
SCENESSE®, which mimics the effects of the naturally occurring hormone ?-MSH, is expected to restore this deficient system, and thus provide efficient therapeutic repigmentation for the patients.
SCENESSE® as an adjunctive therapy with NB-UVB phototherapy may also speed up and assist the repigmentation process initiated by phototherapy and possibly reduce the doses of NB-UVB radiation. Clinuvel has created a video to help explain this process in greater depth.
The company has received significant input and encouragement from leading vitiligo experts worldwide for the use of SCENESSE® as a repigmentation therapy and eagerly awaits the chance to assess the drug in nonsegmental vitiligo.
Where will the trial be run, in which countries?
Clinuvel intends to commence the pilot trial at four leading vitiligo centers: two in the US and two in Europe. No other sites are being considered for this trial. Once regulatory and ethics approval has been granted, more specific information will be made available on these centers.
How can I participate in the trial? 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 is yet to announce inclusion and exclusion criteria for the pilot trial of SCENESSE® in vitiligo. It is anticipated that, once approved by regulatory and ethical authorities, the four centers involved in the trial will look to recruit trial participants from their existing patient groups. As a pilot study, the proposed trial will not look to recruit many participants.
Clinuvel does not recruit trial participants directly, as to do so may jeopardize the integrity of data generated in clinical trials. The company cannot respond to individual requests to be involved in the pilot study of SCENESSE® in nonsegmental vitiligo.
Clinuvel advises individuals with vitiligo to talk to their treating physician which is the best appropriate person to talk to for the different treatment options for their vitiligo, including clinical trials.
Once regulatory approval has been granted, further information will be made available on
http://www.clinuvel.com/vitiligo on whether individuals can register their interest to participate in trials.
When and how do you expect to release results from the pilot vitiligo study?
Clinuvel expects to complete the pilot study of SCENESSE® in vitiligo and publish results from this study during the second quarter of 2011 (1 April-30 June). As a public company listed on the Australian Securities Exchanges (ASX), Clinuvel will first announce its results to the ASX through a formal announcement, before posting them on the company’s website at http://www.clinuvel.com. On this site you can view previous examples of results being
released by the company.
Will Clinuvel run further trials in vitiligo? When will SCENESSE® be approved for use in vitiligo?
Clinuvel expects results from its pilot study in vitiligo during the second quarter of 2011. Until the company has analysed these results, it is not feasible to make any projections on future trials or approval dates.
What is ‘regulatory and ethics committee approval’? How long does this take?
Whenever a company or physician (a ‘sponsor’) wishes to assess a drug in a clinical trial, it must seek approval from the governmental departments or agencies which regulate or control new drugs in a given country or jurisdiction, such as the FDA in the US or the TGA in Australia. This process varies from country to country, but generally requires the sponsor to present a clinical study protocol, which outlines the specifics of the study, and provide scientific rational for their planned trial. These documents must show that the necessary regulatory guidelines related to clinical trials are being followed in the trial protocol.
The relevant regulatory agency will review the study protocol and scientific rationale and determine whether the study should proceed. The protocol is also reviewed to ensure it meets Good Clinical Practice or GCP standard.
This complete process often requires some negotiation between the sponsor, the physicians involved in the trial, and the regulator, to reach a satisfactory conclusion. Generally this process takes 1-3 months.
During or shortly after the regulatory approval process for the study protocol, the Ethics Committees at individual study sites will reviews the protocol to ensure it meets the ethical standards of the particular institute or hospital conducting the study.
To help with understanding the clinical trial process, Clinuvel has published a three part series on its blog entitled The Drug Development Process to read these posts, see part 1, part 2 and part 3. Clinuvel also maintains relevant information on Pharmaceutical Development on its website.
Is SCENESSE® available for purchase anywhere in the world?
Currently SCENESSE® is only available by a physician’s prescription in Italy under a law called 648/96. The 648/96 listing allows Italian physicians to prescribe SCENESSE® to Italian citizens diagnosed with erythropoietic protoporphyria (EPP). For more information on this scheme, see this webpage. SCENESSE® cannot be obtained outside of Clinuvel’s clinical trials anywhere else in the world.
How can I find out more about Clinuvel’s program for vitiligo with SCENESSE®?
Log onto http://www.clinuvel.com/vitiligo