Rare Disease Day focuses on new approach to finding treatment

CAMBRIDGE, UK - Feb 29, 2016 - 2,200 babies will be born in the UK on 29th February, of which 30 will die of a rare disease before they are five years old*. UK charity Findacure believes that existing drugs may hold the key to new treatments and repurposing could save the NHS millions of pounds. It is holding a conference on ‘Rare Disease Day’ to bring together health professionals, researchers and patients to explore how emerging approaches to drug repurposing can give hope to families facing this tragedy.

Dr Richard Thompson, Scientific Officer of Findacure, says: “Only around 400 of the 7,000 rare diseases have licenced treatments, and few of these conditions receive research attention. This leaves patients with little hope of ever receiving a disease modifying treatment, and doctors to prescribe drugs that they believe could benefit their patients ‘off-label’, often with little clinical evidence.”

Dr Thompson explains that while all the drugs are approved for a specific condition, doctors are able to prescribe them ‘off-label’ for other conditions: “Off-label prescription of drugs is actually surprisingly common in the health system. There are elements of uneasiness around it, because monitoring of the treatment isn’t coordinated or widespread; however, when no other treatment option exists, as in the majority of rare disease, it can be the only hope for both patient and doctor.  When properly monitored it can lead to medical breakthroughs by finding new uses for existing drugs. This is known as drug repurposing.”

Where there is evidence from patients, clinicians, or researchers that suggests that certain drugs are beneficial, Findacure is aiming to run clinical trials to provide a more robust body of evidence to support the off-label prescription of drugs in rare diseases.

This is complicated as these diseases are so rare there are often insufficient patients to participate in a trial and there is a lack of appetite from pharmaceutical companies to invest in research when the market is so small.

One of the achievements of the 100,000 Genomes Project has been support for a consistent platform for genomic analysis in the UK, which is providing a means of identifying clinicians that might have candidates for trials. The technology is called Sapientia™ and it supports a more accurate clinical diagnosis for patients with rare diseases by highlighting gene mutations that are associated with disease. By providing a greater understanding of the faulty pathway it is easier to see how a drug can provide a benefit.

Dr Tom Weaver, CEO of Congenica, the company which developed Sapientia, comments: “On average it takes seven years to diagnose a developmental disease; sadly for many children this is too long. Sapientia provides a rapid diagnosis and - crucially - is building a knowledge base of rare diseases and their symptoms. This will help consultants to identify those who could benefit from new treatments, leading to increasing success rates in clinical trials.”

To fast track the search for beneficial drugs, Findacure is developing a new approach to funding trials using Social Impact Bonds.

Dr Thompson explains: “An effective treatment has the potential to both help patients, and save the NHS money. Using a social impact bond, a proportion of these savings can be reinvested to fund further research, creating a win-win situation.”

For example, Findacure’s US-based partner ‘Cures Within Reach’ funded a trial for repurposing the drug sirolimus for the deadly childhood disease Autoimmune Lymphoproliferative Syndrome (ALPS) which requires hospital confinement and expensive forms of treatment.

In less than 30 months and for less than £150,000, their researcher created a mouse model of the disease, cured the mice, and then conducted a pilot human clinical trial, which proved this drug significantly reduced or eliminated symptoms of ALPS in over 85% of the patients.

It offers an average saving estimated at over £50,000 per patient per year over current treatment. This means that if only 10% of ALPS patients in the US benefited from sirolimus it would generate an annual saving of £3M on a total investment of £150,000.

Dr Thompson continues: “Findacure’s development study is focusing on building cost of illness models for specific rare diseases, allowing us to quantify their current cost to the NHS, and the amount repurposed drugs could save the health service.”

Ten clinical diseases will be targeted and Findacure is in the process of setting up a proof of concept study for the first of these, congenital hyperinsulinism (CHI).

Children with CHI are born with hyperactive beta cells in their pancreas, which causes them to over-produce insulin, which removes glucose from the blood. If not detected this can starve the brain of fuel, leading to brain damage or even death. Treatment can involve the removal of the pancreas, consigning the child to a lifetime of diabetes.

Again the drug sirolimus is showing promise as an off-label treatment that can help patients regulate their own blood sugar, and keep their pancreas.

Findacure is confident that the treatments will be affordable. Dr Thompson comments: “As the current plan is to work on an off-label prescription model, the drug couldn’t be marketed for the new rare disease treatment.

“By targeting only generic drugs, the price point will already be low, and any given generic company would struggle to raise it. This should protect the price, ensuring that all partners get the benefit of any successful trials.”

The NHS has been supportive of Findacure’s approach and has indicated that it would like to see the model developed further, to prove it can deliver both cost savings to the NHS and improved healthcare to rare disease patients.

The Social Impact Bond is still at proof of concept. As a non-profit, Findacure rely on the generosity of individuals, trusts and corporates to fund the development of their project. If you would like to support their work, you can donate directly via their website: www.findacure.org.uk.

*3.5m people in the UK have a rare disease, 75% of rare diseases affect children and 30% of rare disease patients will die before their 5th birthday. (EURORDIS)

2200 babies born a day http://www.ons.gov.uk/ons/rel/vsob1/birth-summary-tables--england-and-wales/2014/stb-births-in-england-and-wales-2014.html