Interview: Where do the current and future challenges lie in bringing new orphan drugs to market?

In Clinical Development by Freya Smale

As part of a series of interviews conducted with leading industry experts in the run up to the World Orphan Drug Congress in Geneva, Total Orphan Drugs was delighted to sit down with Mark Rothera, Chief download, clinical development, PTC TherapeuticsCommercial Officer, PTC Therapeutics, Inc. who will be chairing the Clinical Development and R&D session at the Congress which is taking place next week.  Join him for the discussion by booking today >

Total Orphan Drugs would like to take this opportunity to thank Mark Rothera for speaking to us.

From a strategic perspective, where do the current and future challenges lie in bringing new orphan drugs to market?

One of the major challenges I see is demonstrating robust efficacy on a 1- dimensional basis, which can be very challenging in heterogeneous, very rare genetic disorders. If you are looking at rare genetic disorders, many are very heterogeneous in the way they present. Therefore, it is not always obvious what the end point should be or indeed how much impact it could have on a particular end point for regulatory purposes.

And to take that question a bit further, what do believe to be the specific issues of translating rare disease research into a marketed orphan product?

Wow, there are quite a few! One such issue is the need to be clear on the value of the product that you are bringing to the market. Being the first or second to produce a drug that makes a difference to the course of disease in patients with a rare condition, means that you are looking at a drug that is potentially very valuable. In the face of scrutiny from payers, it is important to demonstrate value even in rare diseases. I think you know the best way of doing that is by demonstrating the clinical impact of what you are bringing to the world and also the level of innovation. If you are making a difference to the course of disease then you can justify a high value product to the world. Value is something that is upper most when planning the future. Eventual commercialisation should be a focus of efforts, even from an R&D perspective. Many payers are putting in place HTAs, so you need to think about how this will engage in discussion in the rare disease world as it has in the more conventional pharmaceutical arena.

That obviously puts greater scrutiny on executing an effective and robust clinical development programme. How can developers streamline their orphan clinical development and overcome clinical hurdles?

One of the most effective ways of overcoming clinical hurdles is by being very clear that your endpoints for regulatory approval are well characterised and validated; and that the regulators are supporting the use of those end points. What becomes trickier is when you are pioneering in a field where there aren’t previously validated endpoints from a regulatory perspective. I think for those who choose to be first, the real pioneers in some disease areas where there aren’t previously approved endpoints, this becomes more challenging, more risky but also more rewarding. It is partly a question of where you choose to focus your development efforts.

And with approximately 7000 rare diseases, there are certainly a lot of areas to focus on! Moving to a more strategic focus, what is the current state of partnering like in the orphan drug sector?

I think it’s alive and well! There are many strategic partnerships across different research and development platforms, research platforms in particular, that enable multiple capabilities to be brought together to help resolve questions and issues within the R&D process. I suppose when it comes to development, once you get to the later stages, a big question arises for smaller companies focused on developing in this sector: whether to go for the ‘go it alone’ commercialisation choice and become a fully integrated biopharmaceutical company; or elect a partner and remain an R&D boutique.

So for companies that see partnering as the best way forward, what do you feel are the most important aspects of making a multi-stakeholder partnership successful?

One key example is the tremendous value of partnership between patient organisations and R&D based orphan companies. I think that there are a number of initiatives that would never have got off the ground were it not for that collaboration. For example, for PTC Therapeutics, thanks to the partnership with the SMA foundation and subsequently with RUSH, we were able to identify a lead candidate for the development of a drug for Spinal Muscular Atrophy. This was only made possible by the initial partnership with a patient association. Similarly, for Duchene’s Muscular Dystrophy, very close collaboration over many years with PPMD, helped us to tackle some of the issues of producing the first drug for DMD.

You talked there about initiatives “getting off the ground”, what does the investment landscape look like for early stage research in the orphan drug industry?

Really good! The IPO market has opened up with more IPOs than ever this year. We are one of the companies that have chosen over the last 3 months to go public and have raised significant funds to see ourselves through the next and final phase of development of our lead candidate.

So what does the future hold? What have been and what might be the key game changers altering the dynamic of the orphan drug industry for developers?

One key game changer in my opinion goes back to the availability and selection of the right end points of diseases that are yet to be studied to the point of the development of a drug candidate. There is also the potential game changer that could arise from the development of disruptive technologies, which will enable multiple orphans to be treated with a drug of the same principal. For example, our lead candidate Ataluren treats a subset of patients with nonsense mutations. We believe that there are up to 2400 genetic diseases with a component due to nonsense mutations, so you could envisage one therapy being able to treat a subpopulation of 2400 genetic diseases and that would be a real game changer!

Read more interviews in this orphan drug series
Partnering from the pharma perspective
How to deliver value to patients
Perspective from patient advocates in Sweden
Interview: Surmounting barriers to patient access
Unique opportunities to develop cures for orphan diseases in the Middle East shouldn’t be overlooked
Where do the current and future challenges lie in bringing new orphan drugs to market?
Bringing Biotech Spirit to a Non-Profit Environment
Paving the way for a whole new medical paradigm
Tailoring your reimbursement strategy, step by step, country by country
An Interview With Pfizer on the Orphan Drug Industry: Part I
An Interview With Pfizer on the Orphan Drug Industry: Part II
An Interview with the Chair of the IRDiRC
An Interview with an Orphan Drug Payer