LONDON – Summer has been slow to arrive in Europe this year, something that is maybe a blessing for patients with erythropoietic protoporphyria (EPP), an extreme sensitivity to sunlight, who have been awaiting the market rollout of the first approved treatment, Scenesse (afamelanotide).

The product, owned by Clinuvel Pharmaceuticals Ltd., of Melbourne, Australia, was approved almost six months ago, but the post-authorization requirements laid down by the EMA mean the first prescription is yet to be written.

Now, though, there is progress, as the first convention of EPP specialists took place in Paris on Friday, as part of a commitment to the EMA to train expert physicians and their staff.

At the convention, 33 physicians from 23 centers in 15 countries were instructed in the administration of Scenesse. The extent of the interest in prescribing the drug has exceeded expectations, and Clinuvel said it will hold a number of other expert meetings.

"There is a level of expectation, because patients are pretty severely affected. One told me, it is absolute torture to be looking at a clear blue sky, because that signals the disease onset," said Clinuvel spokesman Lachlan Hay.

EPP is so severe that a placebo-controlled phase III would have been unethical and the recommendation to approve Scenesse was notable for being the first time the EMA had heard testimony from patients during its deliberations on a marketing application.

"We really had a [clinical development] program that was directed by patients. The feedback was phenomenal – some had not been out for decades. We had to push hard to have patients involved in regulatory conversations, but half a dozen of the patients were medically qualified," Hay told BioWorld Today.

In the absence of statistically significant proof of efficacy, Clinuvel is required to establish a centralized European EPP registry and carry out a post-authorization study of all patients. The company will have to provide biannual safety reports to the EMA for the first two years and a data and safety monitoring board will oversee the registry. (See BioWorld Today, Oct. 28, 2014.)

"The past months have demonstrated clinical demand from EPP patients," said Emilie Rodenburger, Clinuvel's director of clinical affairs. It is a considerable task to put in place all the processes to meet the EMA requirements. "Progress is taking longer than we wish for," Rodenburger said.

Special access schemes have been in place in Italy since 2010 and in Switzerland since 2006. Hay said some patients had traveled to Switzerland to access the product. "There is patient demand for treatment at this time of year. Our goal is to be treating patients before the summer," he said.

"This is a fairly big change for us – having focused on R&D for a decade, to be now moving across to the commercial realm," said Hay.

The initial rollout will be in Germany, the Netherlands, the UK and France, where clinical trials were staged, and where there are known patient populations and clinical centers. The treatment of EPP does not fall to one particular specialty, with dermatologists, hematologists and phytobiologists all likely to be involved. "It's a broad church," Hay said.

Clinuvel has agreed on a price for Scenesse in treating EPP with German payers, which it is using as a reference for negotiations in other markets. Hay said the payers recognize EPP needs treating and the company has had "a fairly warm response."

The company intends to put some of the European postmarketing data before the FDA in the hope that it will not be necessary to do another U.S. trial before getting marketing approval. However, Hay said that while the FDA has spoken to EPP patients a couple of times, "it finds it difficult to acknowledge the role of patients.

"It would be hard to generate any different data. You can't do a placebo-controlled trial and EPP patients change their habits; they don't go out in the sun. So how do you measure the effects [of Scenesse]?" Hay said.

Scenesse, a first-in-class alpha-melanocyte-stimulating hormone analogue, promotes the development of pigmentation, protecting patients with EPP from a buildup of protoporphyrin in their skin. Protoporphyrin, a precursor of heme, absorbs light in the visible spectrum, triggering painful itching, burning and swelling on exposure to sunlight or bright indoor lighting. There is no other treatment and sufferers are only safe to go out at night.

EXPANDING USE TO VITIGLIO

While pressing ahead with commercialization in Europe, Clinuvel is awaiting data from a phase IIb trial in which it is testing Scenesse as a treatment for vitiglio. The condition is characterized by patchy loss of skin pigmentation due to the selective loss of epidermal melanocytes. Scenesse administered in combination with ultraviolet phytotherapy, has been shown to promote repigmentation in two U.S. phase IIa trials.

The phase IIb trial, being run at the National Skin Center in Singapore, is testing Scenesse against placebo in combination with phytotherapy. Clinuvel has talked to the FDA about conducting a U.S. phase IIb or phase III study, pending the outcome of the Singapore trial.

"Where you are using Scenesse to treat vitiglio you are giving more regular doses than in EPP," Hay said. Given that, the FDA has asked Clinuvel to conduct a preclinical study. "So we still have a few hurdles to get over," he said.

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