29 February 2020

According to Genomics England, 7% of the UK population will have a rare disease in their lifetime. In the UK alone, this adds up to 3 million people. In recent years the pharmaceutical industry has concentrated on increasing its investment in this population. The therapeutic armamentarium may include medical interventions that both prevent symptoms and offer disease modification.

In 2019 the FDA registered 48 novel medicines of which 21 (44%) were for orphan conditions. Of all the novel drugs, 60%were put through expedited pathways. This is slightly less than in 2018 when 34 of the 59 (58%) novel drugs that were approved were for rare disease. This demonstrates that there is strong and consistent investment in the rare and orphan drug area. The expedited pathways on both sides of the Atlantic are complex, but are an essential component of drug development in the 2020's. At tranScrip, just over 40% of the 34 development products we worked on in 2019 were either for a single rare disease indication or one of the conditions for which they are being developed was a rare disease. During the last 4-5 years, tranScrip has moved away from using single dedicated rare disease specialists working on rare or ultrarare conditions. Now our therapeutic specialist teams all contain experts who have their own experience of using both expedited pathways and the need for early epidemiological, positioning and patient and stakeholder input to the development plans.

The advent of patient representatives in working parties and at scientific advice meetings has added valuable insight to the design of research programmes and the necessity for including outcomes of specific importance to patients. However, we have also learned that with the increasing number of rare diseases programs, progress to approval has become more challenging due to increasing agency hurdles, despite the available expedited regulatory pathways. This is to be expected as the agencies become more familiar with such programmes. The drive to provide evidence-based understanding of the longitudinal progress of a rare condition now demands for epidemiological skills as well as in-depth medical and therapeutic understanding of the patient journey. At tranScrip, this has led to a restructuring of some of our drug development teams to ensure that this variety of skills is applied to programme design so that the vast array of issues can be addressed rapidly, as is required by an expedited programme . Many of our projects relate to the development of immunologically active pharmaceuticals. Some of the late phase pre-clinical programs, for which we have been engaged to design fit-for-purpose regulatory studies, have had the opportunity to be developed for more than 20 indications. Whilst this is challenging, it is extremely rewarding to see these products going into development for diseases where there are no registered treatments.

Whilst there has clearly been huge progress in the number of medications being developed for rare disease, there are serious challenges ahead. There are the ever present ethical and practical issues of how these treatments are paid for by the health authorities in order to allow pharmaceutical companies to recoup their costs. Many recent initiatives have tried to address this, and early consideration of health economics has become standard. However, cell and gene therapies take these considerations to another level and represent an important scientific and medical advancement. Products including Kymriah, Yescarta, and Luxturna have been launched, and many others are in late stage development. With this progress, payers, government agencies, manufacturers and other stakeholders are trying to establish workable pricing models to support such therapies. As participants in the Fierce Biotech Breakfast at the 2020 JP Morgan Healthcare conference heard, the potential to provide a durable or possibly even a curative effect (often with a single administration) leads to a completely different approach to pricing from that for products that may be used for many years or even lifelong. Whilst single use treatments have the potential to provide major cost savings to the healthcare system, charging the patient upfront in one hit to recoup the development costs is clearly not viable to the individual patients. It is essential that we address such pricing challenges otherwise companies will be deterred from investment into this kind of research. It would be tragic to see a situation arising, similar to that with antibiotics, where short course curatives treatments cannot be priced to recoup the development costs thus severely inhibiting pharmaceutical investment.

tranScrip has worked on rare disease development programmes, including registry initiatives, registrations in many therapeutic areas, including respiratory, metabolic disease, neurological disease, bone disease and numerous immunological conditions. To date these products have offered much needed support to patients, but most have not been curable. The horizon for more advanced curative products is very exciting, but there are many rare conditions for which there are no treatments at all. On this Rare Disease Day, please consider supporting the many charities that underpin much of the patient input vital to ensuring that we keep generating affordable, fit-for-purpose medicines for rare disease.

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References:
www.genomicsengland.co.uk/understanding-genomics/rare-disease-genomics/
www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019
https://www.fda.gov/files/drugs/published/New-Drug-Therapy-Approvals-2018_3.pdf