LONDON – Patient power has pushed Clinuvel Pharmaceuticals Ltd.'s Scenesse (afamelanotide) treatment for extreme sensitivity to sunlight over the line, in the first example of the European Medicines Agency (EMA) hearing testimony from sufferers of a disease when making the final assessment of a drug.

When the Committee for Medicinal Products for Human Use (CHMP) sat down to deliberate over the file at the end of September, two patients with the rare inherited disorder erythropoietic protoporphyria (EPP), were there to give their views of the risks and benefit of Scenesse.

The product, a first-in-class alpha-melanocyte-stimulating hormone analogue, promotes the development of pigmentation, protecting patients with EPP from a build-up 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.

While the product met the endpoints of reducing phototoxicity and increasing pain-free exposure to sunlight in a European phase III and a European and Australian phase III trial, a wide variation in response to Scenesse led it to miss the primary endpoints in a U.S. phase III trial.

The lack of robust efficacy data led the EMA to twice extend its review of the file, which Clinuvel, of Melbourne, Australia, submitted in February 2012. Now the patient testimony of improvements in quality of life has finally persuaded the CHMP, which acknowledged the lack of efficacy data is down to the fact that it would be unethical to conduct a placebo-controlled trial where patients were exposed to sunlight.

Scenesse is the first product to be assessed under a one-year pilot scheme in which the EMA will invite patient testimony for treatments that address unmet medical need, but where the CHMP has doubts about the risk-benefit profile. (See BioWorld Today, Sept. 29, 2014.)

Yann Le Cam, CEO of the European Organization for Rare Diseases (Eurordis) said it is a "major breakthrough" that patients have been allowed onto the CHMP after long years of campaigning, albeit in a one-year pilot.

Eurordis runs a program training patient representatives to participate in bodies such as ethics committees, health technology assessment agencies, and now, the CHMP. The two patients who gave evidence on Scenesse were identified and supported by Eurordis. They were from two different countries and had a scientific background, Le Cam said.

Selecting people who know a disease well enough, are able to understand the discussion, articulate the patients' view and speak in public, is not straightforward.

"It's not easy to find the right people; in this case we did," said Le Cam. Live testimony gives a broader view than patient-reported outcomes, he added.

Le Cam was speaking at a conference in London last week, 'New Trial Pathways and Better Patient Data' looking at the general push toward an adaptive approach to approvals, in which treatments are allowed onto the market under controlled conditions.

In addition to the patient evidence scheme, EMA is running a pilot in adaptive licensing, in which it intends to give expedited approval to products in small, defined patient populations and then allow the label to be extended to wider patient groups on the basis of real-world data.

Hans-Georg Eichler, senior medical officer at the EMA, told the conference the agency has now received 29 applications from companies interested in having their products selected to be part of the pilot.

Companies have the opportunity to discuss trial designs under safe harbor confidentiality rules, with the aim of making better use of existing EMA pathways, such as conditional approvals and pediatric investigation plans, which are intended to bring medicines to market faster.

"At first we were worried that no one would come to the party, but the industry did come forward," said Eichler. But although pleased with the response, Eichler said he personally is "somewhat disappointed" by the quality of the applications. "We are still talking in a linear way of going from A to B to C. We can go to a higher level of complexity and intelligence," he told delegates.

Tools are needed to stimulate thinking in the design of pathways. "It's more difficult than you would think," Eichler said. He also pointed to the requirement for a more systematic assessment of patients' willingness to accept the greater uncertainty that is implied in granting an approval before the full risk-benefit profile of a drug is evident, and of the need to establish patient registries and control prescribing.

In the case of Scenesse, the CHMP recommended approval under its exceptional circumstances approval route, a type of marketing authorization given when the applicant is unable to provide comprehensive data on efficacy and safety under normal conditions of use. This information must now be backfilled, with Clinuvel required to put in place a risk management plan, including setting up a registry to collect safety and efficiency data.

Clinuvel said patients have been asking for access to Scenesse for many years and the EMA recommendation is a "landmark achievement." Clinuvel's CEO, Philippe Wolgen said, "It is a privilege to have written pharmaceutical history for those patients."

There are estimated to be 10,000 suffers of EPP worldwide, of whom 45 percent live in Europe. Armed with the European approval, Wolgen said Clinuvel will now look to find the fastest route to approval in the U.S. and Asia.

Scenesse was originally developed as a sun tanning agent, but Clinuvel changed tack in 2005 to concentrate on ultra-violet-related skin disorders. The approval for EPP opens the way for Clinuvel to expand the label for Scenesse, with the treatment of vitiligo, a loss of skin pigment, being the next indication in the pipeline.

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