The medicine man, butterfly children and the business of battling rare diseases
CHANNEL 4 documentaries are well known for their eye-catching titles.
In 2004 the station ran a programme entitled The Boy Whose
Skin Fell Off which chronicled the final months of Jonny Kennedy, who died aged 36 of skin cancer caused by epidermolysis bullosa (EB), a rare disease causing the skin to blister painfully at the slightest friction.
The moving film was many people’s first encounter with the disease and helped invigorate fundraising to support sufferers.
Now one of Ireland’s newest listed companies is aiming to develop a new treatment for EB. Amryt Pharma is led by Joe Wiley (45), who studied in Trinity College, Dublin, before beginning his working life as a medical doctor but then left for the world of business.
“I was in training as a neurologist when I decided to move away from clinical medicine and into the commercial world. I had spent a number of years in clinical medicine treating patients and that’s a hugely rewarding thing to do, but I was attracted to moving to the commercial side because I felt that would give me the opportunity to develop products which would help improve the lives of lots of people... that’s why I jumped ship,” Wiley says.
He became medical director for Astellas Pharma in Ireland and then opened and led the European office of Soffinova Ventures — one of the world’s top healthcare venture capital firms.
At Soffinova Wiley decided he wanted to focus on treating rare diseases and so Amryt was born in August 2015.
Wiley identified a pair of acquisition targets in Germany and Switzerland and took Amryt public in April of this year via a reverse takeover of the Dublin and London listed cash shell Fastnet Equity. That enabled the acquisitions to proceed, giving Amryt its assets.
In a choppy market for biotech, the reverse takeover (involving Fastnet issuing enough new shares to Amryt to enable the latter company to take control) was a good way of accessing fresh capital without having to go through the long, tortuous and expensive IPO process, Wiley says.
His idea was to “acquire, develop and commercialise” products for rare or “orphan” diseases.
Traditionally, pharma companies had been slow to develop treatments for such conditions because of the small number of prospective patients. The incentives improved, however, on the back of the 1983 US Orphan Drug Act, which among other benefits gave tax credits and a seven-year period of market exclusivity — entirely separate to patent status — to companies that had drugs for rare diseases approved by the regulators.
Similar legislation followed in Europe and elsewhere, making the area a more compelling proposition for investors.
“It was clear to governments and regulatory authorities that it’s patently unfair that if you have a diseases that’s rare, that you don’t get drugs developed,” says Wiley.
“Because of the drive to develop products, orphan and rare diseases now are really a strong growth driver of ethical pharmaceuticals across the globe. And in the next number of years that is expected to grow at a compound annual growth of 10pc, with orphan drugs... there’s a huge amount of growth to come in this whole area.”
“Most rare diseases don’t have any treatment, there’s 7,000 rare diseases in the world and there’s only a little over 500 drugs approved for a rare disease. So there’s a huge way to go here.”
I ask whether the exclusivity period granted to developers of orphan drugs raises the prospect of price gouging.
The pharmaceutical world has been beset by multiple scandals surrounding price hikes, but Wiley says his company is entitled to charge higher prices than those attached to more commonplace medicines.
“The controversy has been largely about companies taking older products which have been around for a long time, oftentimes generic products, and increasing the price significantly. We’re not doing that. It’s true that orphan products tend to be priced higher than regular drug products but this is legitimate higher pricing which is recognised by physicians, by payers, by patient advocacy groups and so on.
“Because the numbers of patients are so small, you must charge a higher cost per patient in order for companies to recoup the cost of developing those products, so this is a higher price all right, but it is a higher price which is accepted by governments and by societies as necessary to incentivise companies... otherwise there’d be no products ever developed.”
To reap the financial rewards of developing a successful treatment Amryt is looking to have its topical product Episalvan approved for treating EB in the US and Europe. The product is already approved in Europe as a treatment for so-called “partial thickness wounds” — injuries involving the loss of skin down as far as a layer known as the “upper dermis”.
A patent for its use in treating EB has been granted in the US, and now the company wants to begin a so-called Phase 3 clinical study which Wiley hopes will enable it to bring the product to market for EB by the end of 2019.
“It historically has been called the worst disease you’ve never heard of. And the children who are affected by it are born with very fragile skin, they’re called butterfly children because their skin is equivalent to the fragility of a butterfly’s wings.
“You get open wounds occurring all over the body, these are extremely painful wounds and in some forms of the disease they heal by scarring which can often lead to loss of fingers or toes in the more severe forms.
“Episalvan is a topical treatment that accelerates the process of skin healing and in so doing hopefully will also improve the quality of life of those patients by reducing the pain suffered by the children, and importantly reduce the overall disease burden.
“We are in active discussions with regulatory authorities both here in Europe and the US to get their approval to do the Phase 3 study,” Wiley says.
“Because there’s small numbers of patients your clinical trials tend to be smaller and often you can do one single pivotal study to get approval, which shortens your development time potentially, and the number of patients in that study are smaller so a company like ours can afford to do those studies.”
The company has enough money to continue the process through as far as the back end of next year and will look to raise fresh funding, Wiley says.
“We are looking at all our funding options right now, actively, to fund the further development of our products. Given the late stage nature of our business we have the opportunity to explore both venture debt options as well as equity so we are exploring all of our options.”
Amryt also has a product it calls AP102, which it hopes to bring forward as a treatment for patients with an endocrine disorder called resistant acromegaly. The product recently received orphan designation from regulators in the US — a recognition that a company is developing a potentially important new drug. The status confers benefits including improved access to medical research.
As part of its establishment the company also acquired a skin product called Imlan that had been marketed as a so-called cosmeceutical — a cosmetic product purporting to have some medical benefits. Wiley says the company is evaluating how that could be repositioned.
“[Cosmeceuticals] is not a space we want to be in. [Imlan] is doing about €1m in sales right now and continues to do that without any marketing or promotion whatsoever on our behalf. We are looking at our options to reposition it, we see potential for it... we have some nice data with that product,” Wiley says.
Though Amryt is well advanced in the approval process for Episalvan it’s clearly a risky road ahead. Pharmaceuticals is a risky business — just look at Merrion Pharma, which is in the process of winding down and returning cash to shareholders.
Getting drugs to market is an expensive process and self evidently there’s no guarantee that a drug will ever get approval from the regulators.
“We said from the outset that this company is set up to acquire, develop and commercialise products in rare and orphan diseases. We’ve completed two deals. We are actively looking at other opportunities on an ongoing basis, and we do see some great opportunities out there so that is an ongoing process,” Wiley says.
“On the risk side, the trick in our game is to understand risk and manage it. So when we do deals, we segregate risk in to what we call risk buckets, and then that allows you to delineate the risk you’re taking.
“And what you do is you diligence down those risk buckets as much as you can until what’s remaining in the bucket is the residual risk you’re taking on the deal. The idea is to keep that residual amount as small as possible. We’re very excited about our product in EB, clearly all clinical programmes have risk, but we have done Phase 3 studies previously, all three were positive.”
The Amryt boss is a busy man these days. “I spend my life on a plane right now. I’m travelling extensively to Europe to our businesses, also to potential partners, to the UK to talk with investors, and also increasingly to the US.”
As the approval process continues, he’s probably only going to get busier.
‘It’s true that orphan products tend to be priced higher than regular drug products but these are legitimate higher prices’ ‘I spend my life on a plane right now. I’m travelling extensively to Europe to our businesses, also to potential partners, to the UK to talk with investors, and also to the US’