May 1, 2016 (Vol. 36, No. 9)

Clinuvel Pharmaceuticals Adapts a Tanning Agent to Treat Light-Sensitive Skin Disorders

A tanning agent that hadn’t seen the light of day since the 1980s is getting a lot of attention now that it has been transformed into a medicinal product with photoprotective and repigmentary capabilities. The medicinal product, which represents a new way of treating rare, light-sensitive skin disorders, has a sizeable global market—an estimated 45 million patients suffer disorders that make them potential candidates.

The novel therapeutic is being developed by Clinuvel Pharmaceuticals. The company’s first product, Scenesse® (afamelanotide), shields against UV radiation and sunlight by increasing the levels of melanin in the skin.Scenesse is delivered via a subcutaneous dissolving implant approximately the size of a grain of rice. After the implant is in place, increased pigmentation of the skin appears after two days and lasts up to two months.

Scenesse was approved by the European Medicines Agency (EMA) in 2014 to prevent phototoxicity in adults with erythropoietic protoporphyria (EPP), a condition in which light exposure elicits a deep burning reaction in patients’ skin. The costs of supplying the drug are being covered by health insurers in Switzerland and Italy through those nations’ compassionate use, special access programs. Commercial sales in Europe will begin spring 2016.

Scenesse also is in trials in the United States and Singapore for vitiligo, a depigmentation disease. Recent Phase II results indicate patients with darker skin tones respond best. Accordingly, the company will focus on those patients, evaluating Scenesse as a combination treatment alongside narrowband light therapy.

Clinuvel is evaluating whether a combination of light therapy and Scenesse, an alpha-melanocyte-stimuating hormone analogue, can reduce the number of clinical visits required to achieve repigmentation. Left: A vitiligo patient at baseline. Right: The same patient on clinical trial day 140 following 32 narrowband UVB treatments and four Scenesse (afamelanotide 16 mg) implants. [Images courtesy of the patient and trial investigator.]

Origins in Tanning

“The original melanocortin formulation developed by University of Arizona researchers was envisioned as the ultimate tanning drug,” CEO Phillipe J. Wolgen, M.D., says. The formulation, its developers suggested, could serve to reduce the potential for skin damage in the tanning population. This premise, however, was rejected by regulators, and the formulation languished until 2005, when Dr. Wolgen learned about it while he was working as a hedge fund analyst.

“The two metrics in drug development are efficacy and safety,” he notes. “In 2004, this drug had safety data but no efficacy data.”

Dr. Wolgen, however, understood the drug’s potential. He joined the board of Clinuvel, which was already licensing the drug’s technology, and gradually reshaped the company.

Skin-Deep Mechanisms

In 2006, a scientific paper reported that light therapy caused a pigmentary response. More specifically, Dr. Wolgen explains, “Tanning is a stress response provoked by the alpha-melanocyte-stimulating hormone (alpha-MSH). It’s very local, and very active in certain layers of the skin.”

With that understanding, Clinuvel investigated the mechanisms of pigmentation. It learned that stem cells could be transformed into master pigment producing cells by irradiating the stem cells adjacent to the bulb of the hair follicle.

“These stem cells began expressing receptors that allowed them to become docking stations for our redesigned drug, which stimulates the alpha-MSH in the body,” he says.  Clinuvel also observed that alpha-MSH (and its analogues) may stimulate developing melanocytes following ultraviolet therapy to aid in repigmentation of vitiliginous skin.

Clinuvel’s work suggested that a combination of light therapy and an alpha-MSH analogue such as Scenesse could reduce the number of clinical visits required to achieve repigmentation. Currently, the Scenesse derivatives VLRX001 and CUV9900 are being developed as complementary therapies to Scenesse in the treatment of vitiligo. That work is being done as a joint venture with Singapore-based Vallaurix.

In Europe, Clinuvel also is launching a pediatric development for EPP in children. Finally, Scenesse has applications not only to EPP and vitiligo, but to a number of additional conditions.

Inclusive R&D Model

Clinuvel’s business plan deviates from the usual playbook in its inclusiveness. “When you have a bespoke model for an untested segment of your industry,” insists Dr. Wolgen, “you need to approach the entire development program differently.”

His team began by identifying the top 100 academics throughout the world with an interest in this or related areas of research. “These are the underpaid physicians in the echelons of medicine. The initial challenge was how, with a finite budget, to attract them to our program without reimbursing them,” Dr. Wolgen confides.

“We knew how important their independence would be down the track,” he continues. “We approached them and explained the dilemma. We told them we couldn’t pay for their time except as part of the clinical trials, but we could promise full publishing freedom, both good and bad. There was considerable interest.”

Ultimately, Clinuvel recruited 25 researchers devoted to the disease. When the anaphylactic-like reaction to light was discovered, Clinuvel went a step further and gave these researchers a voice in the decision to develop or discontinue the drug based on scientific evidence. “They understood their scrutiny would have to increase, and they felt empowered,” Dr. Wolgen asserts.

Shift to Commercialization

Since gaining EMA approval in 2014, Clinuvel has shifted from research mode to commercial operations. It has opened a new office in the U.K. for European sales and plans to initiate sales in Europe in spring 2016.

The groundwork began early. The company continued supplying Scenesse free of charge to its clinical trials patients for two years after the trials ended. It couldn’t continue that indefinitely, however, and in 2010 and 2012 convinced Italy and Switzerland, respectively, to cover the cost of supplying the drug for special access schemes. Now that the drug is approved in Europe, Clinuvel is negotiating with individual European nations for reimbursement.

“Most have known for years this drug was coming,” Dr. Wolgen declares. “We disclosed the prevalence and patient numbers we expect during the 10-year European Union market exclusivity, the development costs, and the maximum number of patients who can be treated.” If those targets are exceeded, economies of scale can be employed to lower prices. The response, he says, has been positive.

Clinuvel Pharmaceuticals

Location: Level 5, 160 Queen Street, Melbourne, VIC 3000, Australia
Phone: 61-3-9660-4900
Principal: Phillipe J. Wolgen, M.D., Managing Director and CEO
Number of Employees: 25
Focus: Clinuvel is a global biopharmaceutical company developing therapies for rare, light-sensitive skin disorders, including a treatment for erythropoietic protoporphyria.
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