Amryt Pharma: Realizing Rare Disease Treatments

Joe Wiley, CEO of UK-based Amryt Pharma, is steering a road-less-traveled path from the small-pharma playbook-building a sustainable, commercial infrastructure first, with the hopes of accelerating new rare disease drugs to the patients who need them in Europe and beyond

UK-based Amryt Pharma launched in 2015 as a commercial-stage enterprise focused on developing and delivering innovative new treatments for rare and orphan diseases. The company pursued a different path in taking a commercialization focus from the start, with the aim of identifying late-stage assets and bringing them to market in

Joe Wiley, CEO of Amryt Pharma, based in Greater London.

Europe, the Middle East, and North Africa. Amryt’s in-licensing of and subsequent success with homozygous familial hypercholesterolemia (HoFH) treatment Lojuxta was a milestone in its development, quickly facilitating the company’s transformation from a development-stage to a commercial business. HoFH is a very rare and life-threatening genetic disorder characterized by extremely high LDL cholesterol levels.

Pharm Exec spoke to Amryt CEO, Dr. Joe Wiley, to chronicle the rapid rise of this young company, and to discuss how he aims to maintain this momentum in the changing pharma landscapes of Europe and the US.

PE: Could you outline the Amryt story so far?

WILEY: I set up the business with my partner, now CFO, Rory Nealon in August 2015 and it’s been quite a rollercoaster since then. I’m a medic by training, and before setting up Amryt I worked for Sofinnova Ventures, a US venture capital group, one of the largest investors in biotech in the world. I opened and led the European office for Sofinnova and that role gave me a lot of visibility on all the late-stage drug development companies across Europe. 

I noticed some very interesting dynamics, one being that the quality of the assets being developed and discovered here in Europe were every bit as good and often better than the assets being developed in the US. However, predominantly, the companies that are formed and the number of products going through clinical trials to the market is in the US because of access to capital. When you dig into the numbers, there’s actually 10 times less capital to support European companies developing these assets. We felt that created an opportunity. 

We set out to bring a really great team together, located in and initially focused in Europe. We wanted to be a commercialization business from the start. The way we would get over the access-to-capital issue would be to access the public markets here in Europe faster than you might ordinarily do in the US. In terms of the strategy of that business, the one thing that I’ve learned in 20 years in this industry, both on the investment side and on the operational side, is that if you focus on areas of really high unmet medical need, that’s the best place to be for patients, because you’re developing drugs that patients really need. 

Of the 7,000-plus rare diseases known in the world, there’s only approximately 600 or so drugs available to treat them. Rare disease patients are in desperate need of therapy, as often there’s no therapy available for them at all. This also applies for physicians for the same reasons, and for investors and shareholders because there is higher likelihood of success when there are no other drugs. That’s particularly true in rare and orphan diseases. So we decided to focus on that.

PE: What were the challenges and advantages of building a company that avoids early stage R&D? Did setting up a different type of pharma company lead to any obstacles?

WILEY: We made that strategic choice quite deliberately. We decided early on that we didn’t want to be a discovery company. As you know, in the pharmaceutical industry, the average cost of developing drugs keeps increasing; it’s now certainly north of a billion dollars. That doesn’t mean it costs a billion to develop a product, but it factors in the very high failure rate. Second is the length of time that it takes to develop a drug, an average 14 years to get a drug from discovery to the market. We didn’t want to take that path, because that’s incredibly long, incredibly capitally intensive, and very hard for shareholders to see a return on their investment in a timeframe that would be appropriate for particularly accessing public markets. 

We felt that because there was an opportunity to build a great team with a commercial focus, that would be our core and our niche, and we would be able to identify those assets in Europe and successfully commercialize them and bring them to patients in need. And we’ve been very successful in doing that from a standing start. In December 2016, we in-licensed

Lojuxta, which we leveraged to then build out our commercial infrastructure across Europe and across the Middle East, which constitute the main part of our licensed territories. 

Under our stewardship, we’ve grown the product very significantly. Most recently, we in licensed a gene therapy platform for the treatment of a rare disease called epidermolysis bullosa (EB), which gives us a high-tech pipeline as a platform and potential to create a number of further products. What we’re looking to do now is to add further commercial-stage assets down the channel that we’ve created. We’re truly a billable company at this point because we’ve built our commercial infrastructure; we’ve got feet on the ground across Europe, across the Middle East, and we’re headquartered in the UK. 

Our topical wound care product for EB, AP101, is in a Phase III trial that is being conducted in Europe, South America, Asia, and Australia. It is the largest global Phase III trial ever conducted in EB (a group of inherited connective tissue diseases that cause blisters in the skin and mucosal membranes). We anticipate filing an [investigational new drug application] with the FDA to enable the opening of US trial sites in Q3 2018. 

AP101 is a topical product that we gained from acquiring a German business and works by accelerating wound healing. EB is a dreadful disease. It’s a defect in the gene that codes for the protein that holds your skin together. Children born with this disease are called Butterfly Children because their skin is likened to the fragility of a butterfly’s wings. Even pulling on socks can cause the skin to break. And there’s nothing to treat the disease; no drug has ever been approved. 

Our product has shown promise in a proof-of-concept study in EB and has successfully completed three positive Phase III studies in broader indications, which in fact led to the approval of that product by the EMA in partial thickness wounds in adults. This is a slightly unusual situation in that the product is actually approved in Europe, but has a very broad label. Our vision and our raison d’etre is, however, to focus on the rare disease with the really high unmet need, such as treating patients with the more severe forms of EB, both children and adults. While it’s a very large market opportunity for us, it is also feasible to reach as a small company.

PE:If we could touch on the in-licensing of Lojuxta, how important was that for Amryt’s early development?

WILEY: As I mentioned, from the outset, we wanted to be a commercial business and Lojuxta has enabled that. This is a product that we were able to in-license, which had been launched in Europe in 2013. We saw an opportunity to grow that product, and build out our commercial infrastructure on the strength of that deal. It transformed us from a development stage business to a commercial business overnight. And, importantly, because of how that deal was structured, it allowed us to build out that commercial infrastructure through investing on the back of revenues generated from this product. The revenues of the product actually paid for the roll-out of our commercial infrastructure. 

One of the advantages of focusing on rare and orphan diseases with high unmet need is that the small number of patients affected by the disease means there’s usually small numbers of physicians in specialist centers treating those patients; 

therefore, a commensurately small commercial footprint is sufficient to commercialize the products in this area. That works for us as a small company. Clearly, we can’t launch a primary-care drug where we would have to visit every general practitioner in every country. But in rare and orphan diseases, we can. We’ve signed five new distribution agreements in the last few months, with key partners in the territories for which we have the license.

PE:Can you talk about how you assembled the first management team and the importance of all their experience in getting the company off the ground?

WILEY: I was very fortunate in that, from the very outset, I was working with a tremendous partner and CFO, Rory Nealon. Rory and I have very complementary skill sets. We’re both very transactional. In his previous career, I believe Rory did 12 acquisitions in 14 years at Trinity Biotech, which was another business that grew through acquisition. And for many years, I worked in the venture capital industry, investing in many companies in this area. We were also blessed to have Harry Stratford on board from the early stages, advising us on how he built his company, Shire, and later ProStrakan, from the ground up. We brought in Mark Sumeray, who has vast experience, fairly soon after we had done our first two acquisitions. David Allmond joined us as chief commercial officer, from Aegerion, and he has been very successful at building out our commercial team. 

Somebody said to me that, combined, we have 170 years of experience in the industry. Across the leadership team, we have a great breadth and depth of experience across multiple therapeutic areas and geographies across the globe.

PE:What is your vision for the next three to five years? Are you concerned that you can keep a track on all that expertise as you grow? 

WILEY: A lot of people say that we’ve built a company that looks and feels and operates like a much larger company. That’s a reflection of that senior team and it flows through the rest of the business. We have a manufacturing facility, we’ve put the quality systems in place, we have the necessary infrastructure. We are able to leverage that now into a growth trajectory. Our core strategy is to launch our product that’s in Phase III ourselves in our core markets. We see our core markets as Europe and the US, so we’ll build out our commercial infrastructure in the US on the success of our EB product and we’ll launch that in the US. 

In the meantime, we would like to bring more products into our existing infrastructure, and leverage the infrastructure we’ve put in place, because then we will take advantage of economies of scale. Our strategy is to build and create a sustainable, European-based business for our shareholders and the stakeholders that will grow into the future. 

PE:Talking of Europe brings us to the obligatory question about Brexit. What are your views on that, with Europe being a major part of your plans and your current operation?

WILEY: So far, I would say that the impact has been minimal. Obviously, there’s a concern, for sure. We’re a UK plc operating in a global environment with a pan-European commercial business. So how that separation will work out is of concern. 

There are two points, specifically. One is access to talent. We really hope that there will still be ongoing access to the top talent, because right now we are able to access that across Europe. The second area of concern for us is the unknown, specifically, what will happen regarding the regulatory environment? How that will look post-Brexit. Currently, EMA is in the process of transitioning from a London base to an Amsterdam base. 

In rare and orphan diseases, products are approved through the centralized process, which means that you have a seamless regulatory process to get products approved across the whole European Union. What Brexit will mean for that remains to be seen. We hope and anticipate that the UK will remain in harmony with this process in the future. 

Julian Upton is Pharm Exec’s European and Online Editor. He can be reached at julian.upton@ubm.com