Patients take control of innovation

The paternalistic model for delivering healthcare innovation, in which patients are passive subjects for testing news drugs or procedures - and grateful recipients of any resulting products - is coming to an end.

The Michael J Fox Foundation provides the most recent example of patient power in action. Rather than wait any longer for the old-fashioned model to deliver a reliable diagnostic, the research charity sealed an agreement last week with the drug discovery services specialist BioFocus, UK subsidiary of the Belgian genomics company Galapagos NV, to carry out work on a diagnostic test for Parkinson’s disease.

As the world’s largest private funder of research into this neurodegenerative disease, the Foundation has created a new model for objective-driven research. The $240 million of research it has funded to date fits into a coherent overall plan of improving treatments, helping people to cope with their long-term illness, and finding a cure. Rather than seeing itself as a bit-part contributor, the Foundation has positioned itself at the centre of the network of industry, academics and public funding bodies that are involved in Parkinson’s disease research.

As a result, it claims to have, “fundamentally altered the trajectory of progress toward a cure.” Of course the Michael J Fox Foundation has generous backing from its eponymous founder. But more than money, it has tapped into and orchestrated a grassroots movement of patients and carers. ‘Team Fox’ as it has dubbed itself, may sound as if it is limbering up for an athletics competition, but in fact it is a compelling illustration of patient power in action.

Pharma needs patients as active partners

The pharmaceutical industry’s recognition that patients have become the driving force of innovation crystallised this week, when the European Union’s Innovative Medicines Initiative (IMI), opened a fourth call for proposals. As a €2 billion, 10-year effort to restructure the process of drug discovery and development - and restore the competitiveness of Europe’s pharmaceutical and biotechnology industry – IMI needs patients as active partners, contributing alongside academic teams, small companies and regulators, to link with large pharma companies and, “change the way pharmaceutical research is performed,” Michel Goldman, Director of IMI said as he launched the call.

In short, patient power is reshaping the landscape of medical innovation, pushing pharma and biotech companies into closer relationships with patient groups, persuading regulators to factor patients’ (often subjective) views into their assessments of medical utility, and leading public funders to set out road maps for tackling diseases with unmet needs.

The rise of venture philanthropy

Medical research charities and foundations are not a new phenomenon. What is new is the way in which they are spending their money. In the past, most funding was devoted to academic research, with little attempt to see the results translated through to treatments. Even large charities with technology transfer arms such as Cancer Research UK did not actively fund drug development.

Rather, it was expected that market forces and the traditional commercially-driven process of drug development would take care of that. The US Cystic Fibrosis Foundation is the body credited with dropping the old model of handing out grants passively to academics and looking instead to invest in biotech companies, as a faster route to delivering new drugs.

These investments have much in common with old-fashioned venture capital deals, with formal due diligence and the setting of research milestones, timelines and budgets. But funding apart, there are important advantages for companies of such venture philanthropy, because patient advocacy groups like the Cystic Fibrosis Foundation have access to patients and know all the experts in the field, allowing them to home in quickly on emerging research, and catalyse innovation.

Currently, the Cystic Fibrosis Foundation invests US$70 million per annum in research, with the result that it now has 25 potential new therapies in its portfolio. Demonstrating the power of venture philanthropy to transform treatment, the Foundation’s long-term collaborator Vertex Pharmaceuticals Inc recently announced positive results in a Phase III trial of VX-770, the first therapy that actually corrects the function of the defective CTFR protein that is at the heart of the respiratory disease. On the back of this encouraging data, the drug is expected to receive US marketing approval in 2012.

Backing high-risk technologies

The rise of venture philanthropy has coincided with a decline in venture capital investing in early stage drugs, leaving medical research foundations in an increasingly influential position. This is adding further impetus for innovation, since patient advocacy groups want a different return on investment from traditional venture capitalists. They are interested in finding cures, rather than making money. As a result they are less risk-averse and more prepared to back novel technologies.

An example comes from the British Heart Foundation and its bid to accelerate development of cell therapy to treat the after-effects of cardiac arrest. The Foundation has been funding research since its formation 50 years ago, and in 2011 to date, it has put £35 million into various projects. But earlier this year it launched a target-driven project - the Broken Hearts Appeal - to apply stem cells to the repair of damaged heart muscle.

Launching the £50 million appeal, the medical director of the British Heart Foundation, Peter Weissberg claimed it is now clear that in scientific terms “mending human hearts is an achievable goal.” Given enough funding, “We really could make recovery from a heart attack as simple as getting over a broken leg,” he said.

Not enough clinical trials

There is a palpable sense that medical charities will no longer tolerate the wasted potential that is tied up in the current ponderous and expensive drug development process. In response, they are taking work more usually carried out within companies, into their own hands.

In May this year the Alzheimer’s Society in the UK announced it was to set up a £15 million programme to fast-track the development of new drugs over the next 5 – 10 years. Following a systematic trawl, the Society has uncovered six marketed drugs which it believes have activity relevant to treating Alzheimer’s disease. It plans to make further assessments and move these into clinical development.

Jeremy Hughes, the Society’s Chief Executive hailed this as a “groundbreaking” step, saying, “There are not enough clinical trials for dementia happening in the UK.” The response of patients’ groups now is not only to lobby for someone else to do more research, but to take the initiative and carry out specific projects for themselves.

Nothing about us, without us

Patients’ groups are using advocacy to shape public investment in the diseases they represent. Take for example, the Parkinson’s Action Network in the US, which carried out a full review of the drug development pipeline, from the most basic research at academic institutes, all the way along the discovery and development pathway to Phase III clinical trials. It concluded there needed to be a better system for supporting translational research, prompting the formation of the Cures Acceleration Network, to shepherd therapies from discovery to the point at which the private sector might be interested in picking them up.

Similarly, in February the European Cancer Patient Coalition (ECPC), a body representing more than 300 patient organisations across the EU, persuaded the European Parliament to adopt a written declaration calling for cancer research to be coordinated across the continent. As the ECPC said at the time, “It is not an exaggeration to say that this marks a turning point in cancer research advocacy all over Europe.”

The declaration calls on the European Commission to improve the coordination, cooperation and coherence of pan-European, national, regional and local cancer research activities, avoiding duplication and focusing on unmet needs in cancer treatment.

More specifically, the declaration says cancer research must involve “promotion of partnerships with patient groups, harnessing their specific expertise and knowledge to support accelerated progress in research.” The adoption of the declaration was a huge achievement for the founder of ECPC, the charismatic Jan Geissler, providing an echo of the patient advocacy slogan, “Nothing about us, without us”, that he has done so much to promote.

Patients powering genomics

At the same time as demanding more say in what gets funded, it is increasingly the case that many research projects simply would not happen without the active engagements of patients’ groups. Comparative genomics is a potent case in point, as highlighted by a study of the joint disease ankylosing spondylitis, published last week. The research compared the genomes of 3,023 people suffering from the disease with 8,779 healthy controls, uncovering seven genes that appear to have some bearing on the condition.

As Debbie Cook, Director of the National Ankylosing Spondylitis Society in the UK noted, its members have been donating blood or saliva over the past ten years so that their DNA could be analysed. Without this contribution the research would not have been possible, since it required DNA samples from over 5,000 people with this debilitating disease.

In addition to donating tissue samples for use in current projects, patients’ groups are also proactively setting up and managing biobanks, to ensure that samples are on hand for future research projects. The most impressive example of this is the EuroBioBank network, which brings together eleven repositories from France, Germany, Hungary, Italy, Malta, Slovenia, and Spain. With backing from the EU, it provides DNA, cell and tissue samples to scientists conducting research on rare diseases. Over 440,000 samples are available across the network, with around 13,000 new samples collected each year.

The impetus to set up EuroBioBank came directly from families and patients affected by a rare disease offering to give blood or other biological material for use in research. Research in rare diseases is often held up by difficulties in accessing such samples, and it was recognised that a pan European network of biobanks was needed to harbour and distribute this resource. By creating a critical mass of collections and facilitating the exchange of biological material, the EuroBioBank network helps accelerate research on these diseases.

Pre-empting regulatory delays

So, patients’ groups are venting their frustration at wasted resources and taking action to spark innovation at the lower end of the drug development chain. But they are also putting more pressure on regulators, both to allow drug trials to take place and to push for approvals. For example, patients’ groups representing boys suffering from the muscle wasting disease, Duchenne’s muscular dystrophy (DMD), made a pre-emptive approach to the European Medicines Agency (EMA) to discuss tackling the regulatory issues surrounding the unprecedented level of personalisation inherent in therapies for treating DMD which are coming down the pipeline.

This inherited disease is caused by mutations in the gene responsible for producing dystrophin, a protein which is an essential component of muscle. There are a number of different defects, occurring at different positions on the dystrophin gene and the treatment is so finely-tuned that a different drug will be needed for each defect. So for example, the most advanced product PRO-051, which is being developed by the Dutch biotech Prosensa NV, is expected to be effective in 13 per cent of boys with DMD.

Led by TREAT-NMD, the European network that aims to get new therapies for DMD and neuromuscular diseases to patients as quickly as possible, advocates made the case to the EMA that the usual procedure of applying for approval for each drug individually is not appropriate for treatments that have the same basic structure, but target different mutations.

Nascent innovation

The ankylosing spondylitis study is but one example of the way in which genome-wide association studies are throwing up multiple drug targets. Coupled with insights that have come from the huge advances in biology made in the past twenty years, there is now a vast reservoir of knowledge that is ready to be applied to the development of new treatments. Francis Collins, Director of the US National Institutes of Health, told the annual US Biotechnology Industry Organization convention in Washington DC in June that over the past twenty years the number of diseases in which the mechanisms are understood has jumped from a handful to over 4,000.

Clearly, it is unacceptable that these insights gather dust while people wait for treatments. The thought that the mechanism underlying their diseases is known but nothing is being done to act on this understanding will continue to energise patients’ groups, providing inspiration and a spur for innovation.