This month, we interviewed Dr Nick Sireau, Co-founder and Chairman of Findacure, as part of our Ashoka Series. Founded in 2012, Findacure aims to help patients and find treatments for rare and ultra-rare diseases. Nick outlines his organisation’s unique model, which combines building and supporting patient groups with enabling the ‘repurposing’ of generic drugs. He also shares his views on why the pharmaceutical industry commits so little funding to research for rare diseases and talks about Findacure’s efforts to launch a Social Impact Bond (SIB).
Interview by Stephanie van de Werve, Communications and Marketing Manager at Aleron
Rare Diseases

Aleron: What makes rare diseases so much harder to cure, compared to other kinds of diseases?

Nick: As in the name, they are rare! This creates a whole range of problems: In Europe, a rare disease is defined as one that affects less than 5 in 10,000 people. An ultra-rare disease is closer 1 in 100,000. For instance, my own children have an ultra-rare disease called Alkaptonuria (also know as AKU or ‘Black Bone Disease’), which affects 1 in 500,000 people.

Consequently, problems with rare diseases include doctors not understanding the disease, frequent misdiagnosis, the marginalization and isolation of patients, lack of access to funding for the disease and what they call ‘diagnostic Odysseys’ (with people often seeing 7-8 doctors before getting the correct diagnosis, sometimes after decades).

There are about 7,000 rare diseases affecting roughly 6% of the population at some point in their lives. Up to 3,000,000 people may face such a rare disease. Yet research is still quite limited, as people focus far more on common diseases.

Aleron: Would you say that the reasons for this are primarily financial?

Nick: Yes, because until recently there was no financial incentive for companies to actually invest in research into rare diseases. It is only in the past fifteen years that in Europe an incentive has appeared, in the form of the Orphan Drugs Act of 2000. The original Orphan Drugs Act was passed in the US, in 1983. Such drugs are called ‘Orphans’ because they are orphaned from society and from the medical profession.

Aleron: Are there significant differences in approaches to -or level of interest in- rare diseases around the world?

Nick: Europe, at the pan-European level, is very interested in rare diseases, largely thanks to the lobbying of groups such as EURORDIS. France is way ahead – now on its second national plan for rare diseases – and so are the United States. The UK has taken some time to catch up – and although it is making some progress, it is still too slow.

The Findacure Model

Aleron: How would you describe Findacure’s approach to tackling these rare diseases?

Nick: Findacure is a non-profit social enterprise that does two things:

First, we help new and emerging patient groups for rare diseases to stand on their own feet. We provide them with training in things such as how to be involved in a clinical trial, how to work with industry, how to raise funds (including how to crowdfund) and how to identify more patients with a rare disease.

Second, we do what is called ‘repurposing’ or ‘repositioning’, which is to take a generic drug and show how it can be used to address a rare disease.

20130507 Nick portrait from Ashoka 2
Dr Nick Sireau is a social entrepreneur dedicated to empowering patient groups and enabling them to develop their own treatments through ‘repurposing’ generic drugs. Nick’s involvement with rare diseases began when his sons were diagnosed with Alkaptonuria (or ‘Black Bone Disease’): In 2003, Nick became a trustee of the AKU Society and later became the organisation’s Chairman and CEO. In 2012, Nick founded Findacure, which is dedicated to helping patients and find treatments for rare diseases. Nick is an Ashoka Fellow and holds a PhD in the Social Psychology of Collective Behaviour. He is also the editor of ‘Rare Diseases: Challenges and Opportunities for Social Entrepreneurs’ (Greenleaf 2013).

Findacure Logo RGB LR-01Follow Findacure on Twitter @findacure_fdn and read more at findacure.org.uk

These two programmes work together because proving that a generic drug can be adapted for a rare disease, requires the ability to carry out clinical trials. That in turn requires working closely with the patient group. And that, in a nutshell, is what we do. In a way, what we are doing is filling an existing gap in the sector: We found that there is a big gap in training and supporting patient groups. We also found a big gap in the whole area of re-using generic drugs for rare diseases. And that’s why we decided to get involved in both of those areas.

Aleron: But how does findacure identify those who suffer from these rare diseases?

Nick: In the case of AKU, or ‘Black Bone Disease’, we did a number of things:

In terms of identifying patients, ten years ago we only knew of about four known patients worldwide (and two of them were my children). What we first did was a campaign in the UK, including mail-ins to 50,000 GPs, which provided diagnostic criteria for AKU. This helped us identify a number of patients. We then carried out a global internet campaign, using Google Ads in about 15 different languages, including the main European languages as well as Arabic, Hindi, Urdu and others. This highlighted the symptoms of the disease (such as black urine) so that when people ‘Googled’ them, they would immediately come across our ads.

Using our website and the various local AKU societies we then set up in different countries we able to identify many more patients.

We were also able to identify ‘hotspots’ of the disease. With a genetic disease such as AKU, there is a higher incidence in places where there is a lot of ‘consanguity’ –marriage within extended families. We found such hotspots in Jordan, Quatar but also in the north-west of Slovakia.

 Aleron: And why is drug repositioning so important to tackling rare diseases?

Nick: There are thousands of drugs which are ‘generic’ – which is to say they are no longer covered by patent. When a drug goes off patent anyone can produce it generically, without infringing any patent laws. And at much lower cost. A lot of the drugs you buy off the counter – say aspirin or paracetamol – are generic drugs.

And a lot of these drugs can have various different effects on different parts of the body. For instance, aspirin is used for headaches but also for heart problems – and some people think that it might even have an anti-cancer effect. Other drugs, called ‘Beta-Blockers’, which are made to slow down the heart, also have an effect on migraines, on PSTD and a whole range of different diseases and conditions.

But when a drug becomes generic, industry loses interest in developing it any further, because without the protection of intellectual property it becomes harder to charge a higher price. So what happens is that while these drugs continue to be used in what they were first developed for, no one tries to invest in them for their potential use against other diseases.

Aleron: Have you found social investment a useful approach to funding your work?

Nick: Take the example of a particular drug called rapamycin, which we are starting to develop for a disease called hyperinsulinism – hopefully with funding from a a Social Impact Bond (SIB) we are currently working on. Rapamycin has been used for a number of other indications, such as another rare desease called Autoimmune Lymphoproliferative Syndrome (ALPS). Hyperinsulinism causes the body to produce too much insulin. A child diagnosed with it has to have its pancreas removed, or risk dying. But when an afflicted child has its pancreas removed, it becomes a lifelong diabetic, which is itself very problematic. We have found that rapamycin may also protect against the effects of hyperinsulinism and we are working to prove this.

The way our SIB would work for rare diseases is the following:

For a certain disease, let’s called it ‘Disease X’, we can show, using health economics, that it costs the NHS £100,000 a year at the moment, for all kinds of care and treatment.And yet we have ‘Generic Drug Y’, which could potentially treat ‘Disease X’. But no one has shown effectively how to do it because no one has been  able to raise the funds to do so. What a SIB does is allow an organisation such as ours to say to the NHS: If we can develop this drug successfully and save you hundreds of thousands of pounds a year, can you give us part of those savings, which we can then reinvest in developing another drug, for other rare diseases – producing a cyclical effect.

We are working on this new SIB at the moment and are hoping to launch next year.

Social Impact and Innovation

Aleron: When you started with this work, were you really a pioneer or did you find others who were trying to achieve something similar?

Nick: We did find other patient groups that were doing similar things – almost. We came across groups working on ultra-rare diseases such as Alström syndrome and Behçet’s disease – and found there are a number of patients groups working on individual diseases. But the problem is that each group is working on their own disease and very few of them look at the wider picture.

Then there are some umbrella groups. In the UK there’s Rare Disease UK and the Genetic Alliance, in Europe there is the European Organisation for Rare Disease (EURORDIS) and in the US there is the National Organization of Rare Disorders (NORD). But none of these was doing any work specifically on drug repurposing. And none were providing the practical hands on advice that we’ve been providing to patient groups – at least not in the UK.

Aleron: So what is your vision for Findacure?

Nick: To build a real movement for rare diseases. A strong movement with a real sense of identity, but where patient groups also feel much stronger in developing their own treatments. For our work in drug repurposing specifically, our vision is hundreds, if not thousands of affordable new drugs for rare diseases that are sustainable for health services. Our purpose is not necessarily to compete with industry, but to provide an alternative model.

We are starting with a portfolio of around 10 diseases. We worked with Oliver Wyman, the consultancy, who helped us develop a model and criteria by which we assess which diseases we should work on, based on where we have the highest chance of finding a repurposed drug and developing it further.

Aleron: How successful have you been in raising awareness?

Nick: It’s still early days, but interest has been strong – especially in the medical community, where many medics have been thinking and talking about this problem for a long time. Indeed, some of the founders of modern biology, such as William Harvey – the man who first described circulation and properties of blood as we understand them today – have been saying as early as the 16th century that the study of rare diseases is key to understanding common diseases and human biology in general.

One approach that has been key to raising awareness of our work has thus been looking at the link between rare and common diseases. The fact that the diseases we look at are rare means that they are not always important to enough people. But we are trying to help people realize that studying rare diseases can contribute to the study of more common diseases. For example, my kids’ disease, AKU, is actually a rare form of Osteoarthritis, a common disease which affects 6 million people. Research in the former can help us understand the latter at a deep, molecular level.

The story of how of statins were developed is also a good example: Widely used today in treating cholesterol, they were originally developed through the study of an ultra-rare disease called Familial hypercholesterolemia.

Aleron: When did you become an Ashoka fellow – and how has that helped you and Findacure in practice?

Nick: I was originally elected as a fellow in 2010 for a project called SolarAid. But soon after I rapidly moved over to rare diseases. I have found that Ashoka is fantastic, as it brings together this great network of social entrepreneurs. Beyond that, it has a very strong wider network. For example, in our work on a Social Impact Bond, Ashoka has been instrumental in enabling us to engage with the NHS at the highest levels.  For Findacure, Ashoka has additionally brought credibility and crucial access to pro bono resources.

Aleron: Do you agree with Ashoka that everyone can and should be a ‘change maker’?

Nick: What Ashoka is trying to do is show people the various ways in which they can get involved and make a positive change, wherever they are and at whatever level they happen to be. That’s very much something that I would support. In the rare diseases sector, I see so many people who can make a difference – and yet some people are very involved and some less so. Whatever support we get, we are happy to get!

Aleron: What initially triggered your interest in social entrepreneurship and the findacure vision? Was it more your personal connection or a desire to make a broader social impact.

Nick: It is fundamentally my personal connection to rare diseases that I think really drives it forward for me. But also the fact that increasingly I am meeting more patients who have rare diseases and see what it means to live with one. The reward in our case is that by working with so many patients, we really do see the social impact we are having.

ashoka

Ashoka is a non-profit organization dedicated to finding and fostering social entrepreneurs worldwide. Ashoka is the largest network of social entrepreneurs worldwide, with nearly 3,000 Ashoka Fellows in 70 countries putting their system changing ideas into practice on a global scale.
Founded by Bill Drayton in 1980, Ashoka has provided start-up financing, professional support services, and connections to a global network across the business and social sectors, and a platform for people dedicated to changing the world. Ashoka launched the field of social entrepreneurship and has activated multi-sector partners across the world who increasingly look to entrepreneurial talent and new ideas to solve social problems.