The development of medicines for rare diseases is hampered by limited patient numbers and stringent regulatory hurdles. Once these medicines are developed they must then overcome a series of further obstacles before patients can access them.
There is an increased understanding of rare diseases
Scientific progress, including the improvements in rapid genetic sequencing, has led to an increasing understanding of rare diseases. “This is exemplified by the recent diagnosis of two rare disease patients as part of the UKs 100,000 Genomes project,” says Dr Virginia Acha, Executive Director — Research, Medical & Innovation at the Association of the British Pharmaceutical Industry, the trade body that represents the research-based bio-pharmaceutical industry in the UK.. “This increased understanding of disease — coupled with the EU and USA’s incentives for the development of orphan medicines — has led to an unprecedented number of orphan medicines being granted market authorisations in 2014 and 2015.” Orphan medicines in the EU are defined as those which treat diseases or conditions that affect no more than 5 in 10,000 people
Yet rare disease research is uniquely complex, says Dr Acha, with specific barriers such as limited patient numbers and stringent regulatory hurdles, in addition to the typical challenges faced in the development of all new medicines. But even once medicines for rare diseases are developed and deemed to be safe and effective, they face a number of further obstacles before patient can access them.
Mind the gap
With limited patient numbers, it takes longer to generate evidence of a rare disease medicine’s effectiveness and the volume of sales for these medicines will be, relatively speaking, very low. Ultimately, this has to be reflected in their price. “Yet patients with rare diseases shouldn’t be discriminated against,” says Catchpole. “The NHS has to find the right balance so that everyone can benefit from new medicines.”
The main gate-keeper for new medicines in the UK is NICE (The National Institute for Health and Care Excellence), the organisation that reviews new treatments for both clinical and cost-effectiveness. “One key problem is that, generally, NICE uses a one-size-fits all evaluation approach by applying a fixed cost-effectiveness threshold to judge all medicines, which hasn’t really changed since 1999,” says Paul Catchpole, Value & Access Director at the ABPI. “This threshold can sometimes be accurate for medicines used in larger populations; but, for rare diseases, where the numbers of patients are not high, these medicines tend to do less well when they go through NICE.”
Commissioning route for new treatments
NICE has recognised this says Catchpole; and, in 2012, set up a different kind of evaluation mechanism called the highly specialised technologies (HST) programme. Unfortunately, only a very small number of medicines are accepted onto it every year. The result is that potentially important rare disease medicines can fall through the gap.
There is another route, however. NHS England acts as a commissioner for specialised healthcare services and treatments — including orphan medicines that do not go through NICE. “Where there are new medicines for rare diseases, NHS England’s Rare Diseases Advisory Group (RDAG) takes a view on whether or not to advise that they are commissioned,” says Catchpole. “And this has made some difference.” NHS England is still interested in value for money, he points out, but puts its focus on additionally on affordability and where it should place its investment across all specialised disease areas.
Accelerating Access
So what is the future for the commissioning of orphan medicines? “There is a UK-wide Strategy for Rare Diseases,” says Catchpole. “And the health systems of England, Scotland, Wales and Northern Ireland all have plans in place to respond to implementing that strategy. A review of progress is expected early this year and it will be interesting to see what has been achieved since the strategy was first published”
Then there is the Accelerated Access Review (AAR) which, Catchpole says, aims to speed up access and provide a “joined up” approach to getting game changing medicines to patients faster. “The ambition is to flag up much earlier those medicines which appear, firstly, transformative and have the ability to address a high, unmet medical need; and, secondly, appear to have significant clinical promise. If the AAR can create a joined up system which then supports rapid medicines evaluation and evidence generation followed by rapid commissioning and funding, then patients will stand to benefit hugely — including those with rare diseases.”
