In April 2013, Prof. Paul Lasko assumed the position of Chair of the Executive Committee of the International Rare Diseases Research Consortium, a worldwide consortium of over 30 public and private research funders who collectively have pledged over USD 1 billion for research in rare diseases. The IRDiRC teams up researchers and organizations investing in rare diseases research in order to achieve two main objectives by the year 2020, namely to deliver 200 new therapies for rare diseases and means to diagnose most rare diseases.
Given the importance of collaboration and partnerships to drive forward innovations in the rare disease space, we were delighted to conduct an interview with Prof. Lasko recently and what challenges lie ahead for the IRDiRC and the orphan drug industry as a whole:
Where do the current and future challenges lie in bringing new rare disease treatments to patients in need?
Capturing the natural history of a disease is critical for diagnosis and for the design of effective clinical trials. An adequate framework to support the collection of phenotypic data from patients, that would facilitate data transfer and would enable computational analysis, must be established. In addition, dysmorphologies consequent to many rare diseases have overwhelmingly been described in Caucasian patients, and we have far less natural history information about rare diseases in people of other ethnicities. This is a key reason why global collaboration in this area is so vital.
A challenge for regulators is to find the necessary flexibility to properly evaluate data and accepted when warranted data coming from small clinical trials. Clinical trials involving small populations are unavoidable in the rare disease area where patient numbers are by definition small, often extremely so. Adequate innovative clinical trial methods will therefore need to be discussed – and agreed upon – by all stakeholders, including methodologists, clinicians and regulators.
Finally, establishing appropriate cost models to ensure that treatments are not prohibitively priced, while at the same time ensuring that significant incentives exist for the development of novel rare disease therapies, remains a complex economic and legal challenge.
What are the important aspects of making a multi-stakeholder partnership successful?
Better access to pharmaceutical industry resources by public researchers needs to be facilitated. An immediate focus could be on compounds that have been shelved during the development process, along with relevant data, that could be shared and repurposed for projects other than the original one that would often involve a rare disease. Agreements to provide access to existing proprietary databases describing system-wide responses to compounds could also form the basis of new multi-stakeholder partnerships. Similarly, allowing in silico analysis of FDA- and EMA-approved drugs and their effects could accelerate the creation of public-private partnerships to develop new treatments.
International structures such as IRDiRC are well positioned to facilitate the exchange of information, collaboration between researchers (including industry), and access to international funding mechanisms. IRDiRC has developed a set of policies and guidelines, to which all its members have agreed, that are intended to achieve this, and researchers who are funded by IRDiRC members are obligated to agree to them as well. This active contribution of all stakeholders towards a common goal increases the chances of partnership success by building common trust and providing uniform approaches.
What have been/will be the key game changers altering the dynamic of the orphan drug industry for developers?
Obviously, advances in sequencing technologies have tremendously accelerated the identification of disease-causing genes. This has led to the identification of relevant genetic pathways and the identification of many new potential therapeutic targets. I think that the IRDiRC goal of linking essentially all rare diseases to a causative gene by the end of the decade is very much within reach, and achieving this will increase substantially the variety of potential entry points and targets for drug developers.
Better knowledge about the etiology of rare diseases will also provide additional links rare diseases and other more common diseases. For instance, sometimes a rare disease produces an early-onset form of a common disease, or a more drastic presentation of a common disease. In these cases, treatments directed toward the rare disease may also have benefit for patients with the common disease. Increasing appreciation of these links is changing the industry view of rare disease from that of a niche market to that of a key research area that can impact a broader range of conditions.
How can developers streamline their orphan clinical development and overcome clinical hurdles?
Innovative, open-access models should be considered in order to facilitate early-stage therapy development. Of course, IP issues need to be considered, but emerging models that enable open-access research while still providing incentives for later-stage proprietary drug development could prove to be successful. These models could also encourage the development of public-private partnerships that are critical to accelerate development in an area where there is a large and unmet medical need. Importantly, the risks involved in trying novel approaches to drug discovery may be lower in the rare disease area where, for example, repurposing of existing resources that have little present value may produce substantial rewards.
Approaches like oligonucleotide-based exon skipping therapies and gene therapies that are potentially generalizable to more than one genetic disease are ultimately very attractive, as development costs could be distributed and common procedures for regulatory evaluation could be established. Multi-stakeholder involvement will be essential to ensure that this approach meets developers’ requirements from gene discovery to regulatory approval and reimbursement.
Prof. Lasko will be a keynote presenter on the second day of the World Orphan Drug Congress in Geneva. When asked to provide an introductory insight into what his presentation will cover, he had this to say:
My presentation will address the points above, but will focus especially on the activities of IRDiRC and how I think this organization can achieve its 2020 goals and thus contribute toward improving the lives of people living with a rare disease.
With regard to identifying rare disease genes and developing diagnostics, the larger challenge is on the phenotypic side, not on the genome sequencing side. As discussed above, harmonized access to patient data and samples needs to be established, and industry could greatly enhance the quantity and quality of data available. With regard to therapies novel types of public-private partnerships in my mind have great potential. While substantial technological challenges remain, present approaches to both small-molecule discovery as well as to RNA- and gene-based therapies hold great promise. Efforts to streamline and internationally coordinate ethical and legal aspects of orphan drug therapies as well as to develop economic models that incentivize research while enabling affordability are essential to maximize progress in this area.
If you’re interested to learn more about what’s going on this year’s World Orphan Drug Congress, download the brochure here.