Interview – Clinuvel scores at last, courtesy of patient lobby
Australia’s Clinuvel has been around the block. One of the many ironies along the way is that what started out as its cosmetic product for tanning Caucasians could end up as a prescription drug to treat the pigmentation disorder vitiligo in dark-skinned people.
In the meantime the project in question, Scenesse, became the first ever drug to secure EU approval under an exceptional pathway that relied largely on testimony from patient representatives, Clinuvel’s chief executive, Philippe Wolgen, tells EP Vantage. He believes that 28 other companies have made filings under this pathway since Scenesse’s approval in December.
US readers might find it hard to believe that it is only now that the EU review process has sought direct patient input. In stark contrast the US FDA has blazed a trail in giving patient lobbies a voice – at the agency’s expense – as followers of the Duchenne muscular dystrophy space will be well aware.
Scenesse’s EU filing, for preventing the ultra-rare light intolerance disorder erythropoietic protoporphyria (EPP), had been submitted back in early 2012. The project had met some study endpoints, but the protracted delay was a result of the regulator getting to grips with some pretty unique ethical questions.
Mr Wolgen explains: “EPP patients have lived since childhood with a disorder that forces them to stay indoors. If they go beyond that threshold they know that they’ll pay the price by burning themselves.
“That’s called self-limiting conditioned behaviour, and it was the first time the EMA had come across it. Running a trial ... how do you force these people to go outdoors? You can’t burn them on purpose.”
It was thus unethical to expose patients to any more studies, and on the strength of patient and physician testimony that Scenesse had a dramatic impact on life quality the exceptional EU approval was granted.
A few months earlier Clinuvel had been the subject of a takeover approach by Retrophin (Retrophin’s bid to end Clinuvel’s wilderness years, July 28, 2014).
Mr Wolgen calls this either a “naive” attempt to bring in a rare disease drug on the cheap, or a smart way of increasing the value of an equity stake Retrophin already owned. “Our shareholders didn’t want to sell at that price – and not six weeks before EMA approval.”
Since the approach was rejected Retrophin’s CEO, the controversial ex-fund manager Martin Shkreli, has left, and there has been no further direct dialogue, though the US biotech still owns about 6.5% of Clinuvel.
The focus on EPP as a “gateway to the market” came only after a long and futile attempt to develop injectable melanocyte-stimulating hormone, Scenesse’s active ingredient, as the tanning agent Melanotan. Back then the company was known as Epitan, and Mr Wolgen was an equity analyst.
Another irony is that he had a sell recommendation on the group, believing that “no global regulator would ever accept” an injectable cosmetic – a fair point. It was only once he saw the safety data that he realised that complete change was needed, and became a director before being appointed chief executive in 2005.
On his watch the group also flirted with developing CUV1647, as Scenesse was then known, for actinic keratosis and polymorphous light eruption, though he now accepts that there was no real regulatory pathway here.
But early data did show that the molecule had protective properties in a specific band of light, so Clinuvel started looking for “disorders that are caused by [that wavelength]”, says Mr Wolgen. “EPP was the most severe of the lot.” The plan now is to launch Scenesse in the EU, in preparation for which Clinuvel is setting up a European headquarters in the UK.
For the US the company has two EPP studies that it deems positive, though it also plans to supplement an FDA filing with six months’ safety data from its five-year EU post-marketing commitment. Then there is what Mr Wolgren sees as the big game changer – the pigmentation disease vitiligo, whose treatment he says would be a breakthrough.
Financially this is interesting because it is a bigger market than EPP, though this also creates a pricing conundrum since orphan pricing will be pursued for EPP.
In any case Scenesse will never command Soliris-type pricing, simply because it is not treating a life-threatening disorder, says Mr Wolgen. "There is a premium... but it has to be within limits.” A phase II vitiligo study was published in JAMA, and he says two pivotal trials will be needed for US filing.
Remarkably, the chief exec reckons he can get the job done without another equity raise: “We typically are very cautious of dilution. If everything goes well then I hope we won’t need one.”
But first Scenesse needs to succeed in EPP and break even. And of how big a prize vitiligo is there is no doubt in Mr Wolgen’s mind: “It would transform the company both medically and financially.”