Clinuvel has  announced positive interim Phase III results from the first of the trialists to complete a 12 month study in Switzerland. The 14 patients in Switzerland will form part of 101 to undergo long term study around the world. Further participants and Europe and Australia are also taking part in the trial.

This is good news for those who might want to try afamelanotide, it is one small step closer to being approved.

Trial participants received subcutaneous doses of 16 mg of afamelanotide or placebo, blinded, alternating every 2 months for a period of 12 months. The dose is delivered via a bioabsorbable implant around the size of a grain of rice, injected under the skin.

The trial’s main measure of success was a reduction in the pain experiences during an episode of phototoxity. The pain associated with EPP is described as intolerable, causing blistering  and swelling.

The second measure of effectiveness of afamelanotide was melanin density which is seen as skin darkening.

Interestingly the 14 patients involved in the trial asked to continue to take the drug for a further 12 months – such was their benefit. This request was granted.

This interim, small trial didn’t show that afamelanotide reduced the number of phototoxic episodes, rather reduced the severity.

Clinuvel Pharmaceuticals announced in mid 2008 that they had been granted orphan-drug status for afamelanotide to treat the skin condition erythropoietic porphyrias. Orphan drug status is granted to new drugs that treat rare conditions and is used as an instrument to obtain accelerated review by the FDA. The FDA allows tax reductions and market exclusivity for orphan drugs to encourage otherwise un-profitable drugs targeting rare conditions to be developed. See a recent post for more information about when afamelanotide will be available.

Clinuvel are “on schedule in our development of afamelanotide and look modestly but confidently ahead to late 2009, when we anticipate the final Phase III results.”

For more details, see the release from Clinuvel to the Australian Stock Exchange.

Related Articles

• Photoprotection expertise from Clinuvel
• Afamelanotide (Clinuvel CUV1647) gets orphan drug status in the US

The Independent: Warnings over ‘injectable tan’ product

People seeking a glow this winter should avoid an "injectable tan" being sold illegally, regulators warned today.

The Medicines and Healthcare products Regulatory Agency (MHRA) issued a notice over an unlicensed product called Melanotan.

It is being advertised and sold illegally on the internet and in some tanning salons and body building gyms

From the BBC: Unlicensed tanning drug use rises

A growing number of people in the UK are injecting themselves with an unlicensed tanning drug, a BBC investigation has found.

Melanotan is still undergoing clinical trials but is sold illegally online and in salons and gyms, Newsbeat reports.

It is a synthetic hormone which stimulates the body’s production of melanin, a substance that gives the skin its colour.

Experts are worried that the long-term effects are not yet known.

The BBC story links to several videos from users of and also opponents to Melanotan.

From The Daily Telegraph: Illegal tanning injection on sale in gyms and online

The Medicines and Healthcare products Regulatory Agency (MHRA) has said that injecting Melanotan could have serious side-effects.

The self-tanning product, which has not been official safety-tested, is being illegally sold over the internet and in some tanning salons and body building gyms.

The chemical boosts the body’s production of melanin, the natural substance that gives skin its pigmentation and helps protect it from the sun’s rays.

There has been a rapid increase in the number of people seeking such drugs, who want an all-round tan but are unwilling to subject themselves to potentially damaging UV light from sun beds.

But David Carter, from the MHRA, warned: "Don’t be fooled into thinking that Melanotan offers a short cut to a safer and more even tan. The safety of these products is unknown and they are unlicensed in the UK."

He said the side effects could be extremely serious.

It is obviously a pretty big thing to get this sort of massive coverage from papers and online in the UK.

I sometimes get the impression that the online communities are over represented by those who are willing to take risks with treatments. Forums are full of people sharing anecdotal information about how to supposedly safely use unapproved treatments. Certainly the internet and the whole globalisation of drug development and testing has made the exchange of this sort of information easy.

How about you ? are you willing to try unproven and risky treatments ?

Related Articles

• Photoprotection expertise from Clinuvel
• Afamelanotide (Clinuvel CUV1647) gets orphan drug status in the US
• Melanocorp gets warning from FDA for melanotan II
• melanotan (epitan) offers sun protection for fair skin individuals

As some background: Melanotan is the proprietary name for afamelanotide (CUV1647) which is being development by Clinuvel Pharmaceuticals. Afamelanotide has been designated by the world health organisation as the International Nonproprietary Name for the melanocyte stimulating hormone under development by Clinuvel.

Clinuvel is promoting this drug as a photoprotective agent, firstly against the rare condition Erythropoietic Protoporphyria (EPP).

Clinuvel have an excellent web site dedicated to photoprotection – the conditions, current and future treatments, expert opinion and news updates.

If you are interested in ;

• Actinic Keratosis (precancerous lesions of the skin)
• Squamous Cell Carcinoma (malignant tumour of the skin)
• Erythropoietic Protoporphyria (a rare inherited metabolic disorder of the heme pathway)
• Polymorphous Light Eruption (a distressing seasonal skin condition likened to sun poisoning)
• Photodynamic Therapy and Phototoxicity (phototoxicity after PDT treatment)
• Solar Urticaria (anaphylactic reaction to sun)

then have a look at their excellent Photoprotection website.

Related Articles

• Afamelanotide (Clinuvel CUV1647) gets orphan drug status in the US
• Clinuvel trialling CUV1647 (melanotan) for skin cancer for transplantees
• melanotan: could it cause skin cancer ?

Clinuvel Pharmaceuticals has announced that they have been granted orphan-drug status by the FDA to treat the skin condition erythropoietic porphyrias. Orphan drug status is granted to new drugs that treat rare conditions and is used as an instrument to obtain accelerated review by the FDA. The FDA allows tax reductions and market exclusivity for orphan drugs to encourage otherwise un-profitable drugs targeting rare conditions to be developed.

Afamelanotide (formerly Melanotan) is currently being tested by Clinuvel to treat 3 UV related skin disorders and 2 cancer related treatments:  Erythropoietic Protoporphyria, Phototoxicity associated with Photodynamic Therapy, Polymorphous Light Eruptions, Actinic Keratosis and Solar Urticaria.

The official answer to whether afamelanotide can be used to treat rosacea is given via Clinuvel’s FAQ:

Could afamelanotide (CUV1647) be used to treat Vitiligo or Rosacea?

Clinuvel is not currently testing for the indications of Vitiligo or Rosacea, and at present no clinical trials are planned for the foreseeable future. By subscribing to our database, you will receive company updates on any clinical trials.

Despite these official designations, there continues to be interest in whether afamelanotide or Melanotan 2 can provide any benefits for rosacea symptoms.

Melanotan is the proprietary name for afamelanotide (CUV1647) which is being development by Clinuvel Pharmaceuticals. Afamelanotide has been designated by the world health organisation as the International Nonproprietary Name for the melanocyte stimulating hormone under development by Clinuvel.

Note that Melanotan 2 is a different peptide to afamelanotide and is not connected with Clinuvel Pharmaceuticals. Afamelanotide is being promoted as a photoprotective product, with any cosmetic tanning effects being downplayed.

[Update:]

When will afamelanotide be available ?

What does this announcement mean for the availability of products based on afamelanotide ? Sadly, it is still difficult to say – even if everything goes well; when you might be able to get hold of it.

Here are the best comments towards an answer that I can find so far; (this is all corporate speak, sorry).

some quotes from Clinuvel CEO Philippe Wolgen:

"While the drug continues to exhibit its pharmacological action, one could say that commercialisation has now become a function of our execution and ability to test the drug in the required amount of patients. However, the worldwide management of an orphan indication is far from simple and still bears risks. Physicians and patients remain our most precious assets for Clinuvel to be successful in our efforts to commercialise afamelanotide."

and

"The current statistics demonstrate that the FDA is looking at novel drugs more critically than ever. According to the FDA, there were only 17 new approvals for new molecular entities [in 2007]"

and

"In afamelanotide, we identified a first-in-class drug which delivers novel pharmaceutical activity. We anticipate and plan to file for our first Investigational New Drug (IND) this year, 2008. Much technical work to generate compelling data on the drug and formulation has been done over the past 10 months to compile a dossier that meets US regulatory standards. Our one and only goal is to build a dossier that will be robust enough to withstand critique by US FDA examiners, all set against background of stricter regulatory review process."

Related Articles

• melanotan (epitan) offers sun protection for fair skin individuals
• Clinuvel trialling CUV1647 (melanotan) for skin cancer for transplantees

The trial will continue for 2 years and will involve 150 patients receiving a dose every 2 months.

This will be the first trial for skin cancer, previous CUV1647 trials have been for  Polymorphic Light Eruption (PLE) and fair skinned individuals.

The Courier Mail and Herald Sun lead with a quite enticing sentence –

A PILL that gives a perfect tan in two days and may prevent skin cancer could be available within two years.

Trials begin on ‘perfect tan in two days’ pill

Aaaah if only it was that easy.

It is definitely a good move ; finding a main stream condition like skin cancer to trial against. This will surely speed up the approval process of this melanin stimulating hormone. Lots of work to be done to meet the suggested 2010 approval date.

I think the "grain of rice under the skin" sounds so much better than regularly sticking a needle into your side as those experimenting with Melanotan II describe !

From: Our Product > CUV1647

In-vitro studies demonstrated that CUV1647 is between 10 to 1000 more potent1 than our endogenous (natural) peptide, a-MSH. In fact, clinical studies conducted by Clinuvel have confirmed the increased effects by CUV1647.
…
A subset of this program will be a study to determine the effects of CUV1647 in immune-compromised individuals. These subjects will be chosen from a population of organ transplant patients who are particularly prone to develop AK’s and skin cancer after only minimal exposure to UVR.
…
Clinuvel Pharmaceuticals has the worldwide licence to intellectual property covering the use of analogues of -MSH invented by scientists at the University of Arizona.

Related Articles

• Melanotan causing vision problems ?
• melanotan: could it cause skin cancer ?
• topical forskolin: possible rub on tan
• Melanocorp gets warning from FDA for melanotan II
• melanotan (epitan) offers sun protection for fair skin individuals
• Steve’s Melanotan 2 Log thread at the Rosacea Forum.

FDA Issues Warning Letter to Melanocorp, Inc. For Illegal Sale of Melanotan II

Melanocorp, Inc. advertises the product Melanotan II on its Web site as an injectable tanning product, with additional claims that it is effective in protecting against skin cancer and rosacea (a flushing and redness of the skin). These claims cause Melanotan II to be classified as a drug under the Federal Food, Drug and Cosmetic Act, as well as a new drug because there is no evidence that it is generally recognized as safe and effective for its labeled uses.

I’m still of the impression that it is too early to be getting excited about Melanotan and rosacea. There seems to be too many unanswered questions about efficacy and side effects. So here we can see the FDA stepping and saying that it is too early for it to be generally available.

Related Articles:

• melanotan (epitan) offers sun protection for fair skin individuals
• melanotan: could it cause skin cancer ?
• Melanotan causing vision problems ?

My name is Robert, I’m 23 and I had been using MT 2 for over 1 year with great results. However, recently I got vision problems (with gradual onset) and thus went to see an ophthalmologist. I was diagnostized (sic) with a severe form of central serous retinopathy (CSR). Although CSR rarely leads to blindness, usually some vision impairment remains. There is no effective treatment for this condition.

She also found a rather big nevus (mole) on the choroid in my left eye which hasn’t been there before (have had an eye exam in the past). This cannot be removed and have to be monitored for the rest of my life because it may lead to cancer at some point. She had no idea regarding the cause. Apart from being a bit myopic, my eyes were perfectly healthy before. I didn’t tell her about Melanotan by the way.

A recent newspaper article asked the question melanotan: could it cause skin cancer ? As I mentioned in this article, caution is definitely required when trying new treatments, especially when they are available before being FDA approved.

I’d also like to see the question of whether stimulating the production of melanocytes (which then produces the melanin thus a tanned appearance) is in anyway linked to the possibility of being susceptible to melanoma. If you know of any research for or against this then feel free to leave a comment below.

This article from the DailyMail is offering some warnings about being too quick to jump on the Melanotan II bandwagon. It is worth remembering on top of all of the warnings below, that Melanotan specifically as a rosacea treatment is also something we know very little about. I think that the combination of rosacea sufferers desperate for relief, the relative ease of obtaining Melanotan, and the fact that so little is known about its effects, is a recipe for dangerous outcomes.

Pretty pills: The dark side of the latest underground beauty trend

…

The drug, a synthetically produced hormone, was developed by researchers at the University of Arizona to combat skin cancer – it worked by increasing the levels of melanin, which is the body’s natural sun protection system.

…

However, Melanotan II was not a simple pill. It’s a hormone, which means it can’t be swallowed, as the chemicals in the gut would destroy it. It can, however, be introduced into the body through an implant under the skin or via an injection.

It has not yet been approved by the FDA in the US, nor is it a licensed drug in Britain. But this doesn’t mean it’s not easily available.

Several websites around the world, including one in the UK, sell Melanotan II and give users detailed instructions on how to dissolve the drug in water and inject it.

…

Alongside the potential side effects of nausea and flushing, some users are reporting that existing moles and freckles become darker, and that new moles and freckles also form.

Could it be that a product developed to tackle skin cancer might actually cause it? The honest answer is that we just don’t know.

Mark Birch-Machin, professor of molecular dermatology at the University of Newcastle upon Tyne, thinks that the original study into what the drug is capable of has some merit, but stresses that our knowledge of its application and its side-effects is patchy.

“Melanotan II hasn’t been around long enough for us to be able to look at the long-term effects this hormone could have on the body,” he says. “And taking any drug that hasn’t been extensively trialled will always have its potential dangers.”

Further Reading ;

• melanotan (epitan) offers sun protection for fair skin individuals
• reapply sunscreen to avoid skin damage
• micronized zinc oxide dimethicone a safe sunscreen
• topical forskolin: possible rub on tan

From Rub On a Tan and Prevent Skin Cancer?

To figure out what’s going on under the skin, Fisher and his team studied red-haired, fair-skinned mice. Like people with red hair and light skin, these mice didn’t tan, but instead burned when exposed to the sun and its ultraviolet rays.

Melanin is manufactured when a chemical known as cyclic AMP (cAMP) stimulates melanocytes, the melanin-producing cells in the skin. Different people produce different levels of cAMP. People with red hair and fair skin tend to have low levels of cAMP.

Levels of cAMP are controlled by a hormone called melanocyte stimulating hormone (MSH). The reason that fair-skinned, red-haired mice have low levels of cAMP is that the receptor for MSH, which is called MC1R, is shaped differently and can’t be effectively stimulated by MSH. The result is fair skin, because less pigment is produced.

Fisher and his colleagues believed that this pathway to melanin production could be repaired in the fair mice. To test this theory, the researchers used a compound known as forskolin on the mice because it’s believed to raise cAMP levels.

Indeed, after forskolin was rubbed on the skin of the mice, their skin darkened. According to Fisher, the tanning process appeared to be indistinguishable from the normal tanning process that skin goes through when exposed to sunlight. And, he said, the mice didn’t have the same inflammatory response in their skin after being exposed to the sun. Additionally, the researchers didn’t notice any ill effects from the treatment, he added.

But, Fisher said, “Long before this could be recommended for people, it has to be rigorously tested. We have to be sure what we’re doing is safe. We don’t want to cause problems in people who are otherwise healthy.”

• Wikipedia: Melanotan, Forskolin
• Fermentek: Forskolin
• Rosacea News: melanotan (epitan) offers sun protection for fair skin individuals
• Rosacea News: reapply sunscreen to avoid skin damage
• Rosacea News: micronized zinc oxide dimethicone a safe sunscreen

Melanotan, [Nle4, D-Phe7]-a-MSH, significantly increased pigmentation and decreased UV damage in fair-skinned white volunteers, Ross Barnetson, MD, Sydney University, Sydney, NSW, Australia

Epidermal melanin can reduce some of the effects of UVR, which is the major cause of skin cancer. To examine whether induced melanin can provide protection from sunburn injury, we recruited 79 subjects into a clinical trial with the potent synthetic melanotropin Melanotan, delivered by subcutaneous injection into the abdomen at 0.16 mg/kg for three 10-day cycles over 3 months. Sixty-five subjects completed the trial and, compared with placebo, the skin melanin density, measured by reflectance spectroscopy, increased significantly in all Melanotan-treated subjects. The highest increases were seen in those volunteers with the lowest baseline skin melanin levels. In subjects with a skin type associated with a low MED at baseline, melanin increased by an average of 41% (from 2.55 to 3.59, P<.0001 vs placebo) over 8 separate skin sites, compared with only 12% (from 4.18 to 4.70, P <.0001 vs placebo) in subjects with a high MED skin type. Epidermal sunburned (apoptotic) cells resulting from exposure to 3 X an individual’s MED exposure of solar-simulated UVR were reduced by more than 50% after Melanotan treatment in the volunteers with low baseline MED. DNA damage, in the form of thymine dimer formation, was also shown to be reduced by 59% (P < .0033) in the basal layer of the epidermis of this group of subjects. This study has shown for the first time the potential ability of a synthetic hormone that augments melanin production to provide photoprotection to people who normally burn in direct sunlight.

Author disclosure: Consultant to Epitan Ltd. 100% sponsored by Epitan Ltd, Melbourne, Australia.

Poster Discussion Session P2621, American Academy of Dermatology, 64th Annual Meeting, March 3-7 2006, San Francisco.

Supplement to Journal of The American Academy of Dermatology, March 2006, Volume 54, Number 3. JAAD Poster Abstracts Online (29Mb)

Featured Product:

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