Major change for rare disease treatments on way, signals MHRA

Central to this reform will be tackling the unique barriers that currently prevent life-changing rare disease therapies from reaching patients, like small patient numbers and difficult evidence generation, while maintaining safety.   

Around 3.5 million people in the UK – one in 17 – live with a rare disease, equivalent to one child in every classroom. When carers are included, this community is larger than the population of London. Yet fewer than 5% of rare diseases currently have an approved treatment. The average diagnostic journey takes 5.6 years, and 30% of affected children die before the age of five. 

The cost of delayed diagnosis and limited treatment options is estimated at £340 million annually, with a further £4.7 billion in health-related disability costs and a £14.9 billion annual loss to the economy. A new paper sets out how the MHRA is thinking to change this. It commits the UK to major reform and is a huge signal that significant change for rare disease patients is on its way. 

Supporting the development of the reforms is a newly formed Rare Disease Consortium, which includes patients and their representatives, academics and industry.

Julian Beach, MHRA Executive Director, Healthcare Quality and Access, said: "The UK has the ingredients to be a global leader in rare disease therapies, with a rich academic base, a single provider of genomics and the unique, diverse datasets of the NHS. The challenge is bringing all these elements together, which our new framework will do. 

"There is still more work to be done, but I hope this paper reassures all those affected by rare disease that we are listening and are prepared to take bold action to speed the path from discovery to delivery, while maintaining strict standards of safety."

It is more challenging to develop a therapy for a rare disease than for a more common disease like diabetes or hypertension. With small, scattered patient groups and limited scientific understanding of the condition, recruiting participants and conducting clinical trials can be difficult and expensive, making it much harder to gather the evidence needed to prove that a treatment works. This also reduces the financial incentive for companies to invest. 

Advances in science and technology are now enabling highly individualised treatments, even for relatively common rare diseases that affect several thousand people in the UK. Gene-based therapies such as CRISPR or mRNA can be tailored to target specific patient subgroups. In the case of CRISPR, a treatment may even be designed for a single individual based on their unique genetic profile, despite many others sharing the same condition. 

Currently, each new rare therapy requires a separate route through regulatory approval, including an approval to get the clinical trial set up and then an approval to be marketed in the UK (known as a marketing authorisation or licence). This approach is costly and inefficient, making it unviable to develop multiple highly targeted treatments. 

While the framework won’t be published in full until next year, the paper outlines some bold ideas, including whether an early, single approval could be issued for both a clinical trial application and marketing authorisation based on compelling but limited evidence. This approval would be granted with a strict safety monitoring plan with real-world evidence review at a set frequency.  

The paper also sets out:  

• how to better share evidence in the UK and globally to pool scarce data   

• Whether a single approval could be issued for a therapy, even where there is a variable component tailored to an individual’s characteristics  

• the importance of strengthened post-market surveillance   

• better health system alignment in the UK and internationally     

This work supports the Government’s Rare Disease Action Plan, as well as the long-term plans for the NHS and life sciences sector.