The Empowerment of the Rare Disease Patient

The stakeholders in healthcare in the developed world are conventionally divided into three ‘P’ words: patients, payers and pharmaceutical companies. In addition, there are a couple of other more minor players, namely physicians and pharmacists. Recent developments have, however, dramatically increased the importance and changed the role of one of these participants, the patient community. This is so for a number of reasons. First, the commercialisation of niche products for rare and orphan drugs has become the most favoured growth opportunity over the conventional mass-market ‘blockbuster’, and development of drugs in these areas is dependent on access to patients in clinical trials. From the other perspective, patients with rare conditions are increasingly organised into communities with a voice, and they are using their collective power to get what they want, namely access to better medicines. And finally, pharma companies are forming alliances with patient groups to further their case for payers to reimburse expensive medicines. Rare and orphan diseases demand compassion to a much greater degree than more common conditions. Patients are much more likely to be ill as a child, and from inherited genes, than as an older person. Among rare diseases as a whole, 80% have a genetic cause, and many of them are monogeneic – patients suffer through the accident of birth, not as a result of adult behaviour. For a patient with a progressive, life-limiting chronic condition, the urge for speed in drug development is critical; especially as for over 90% of the 7,000-8,000 rare diseases, an approved drug does not exist. Drug repurposing, as I will refer to later, is a common theme. Putting all this together, in an age of social media, the capacity for self-organising communities to further the aims of rare disease patients can be allied with their strong motivation to do something either for themselves or their ill relatives. Their efforts are then assisted by a pharmaceutical sector that is at least actively listening, or even willing to assist. These patient groups demand that healthcare resources are allocated, even when such resources are scarce (witness the charity Action Duchenne, which parked the wheelchairs of over 100 teenage boys outside the UK parliament in order to campaign for reimbursement of the first approved drug for the condition). Some of the carers of rare disease patients (or even the patients themselves) go to great lengths to educate themselves about the relevant condition. And from this position, it is an easy step for them to ask themselves a simple question, what more can a patient or carer do to improve therapy? A great example of this phenomenon is that of John Crowley, who has two children with a severe neuromuscular lysosomal storage disease called Pompe Disease. First, he founded a foundation to raise money for the condition, then he got a job with Bristol Myers Squibb in order to immerse himself in the pharmaceutical business. Then he founded Novazyme Pharmaceuticals to develop an enzyme replacement therapy for his daughters’ condition, which was subsequently acquired by Genzyme corporation and the treatment marketed. Later, he became CEO of another company (Amicus Therapeutics) which is also engaged in lysosomal storage disorder research for Pompe and Fabry diseases. He was the subject of a book about his efforts to save his children, and subsequently the story feature in a film called Extraordinary Measures starring Harrison Ford in 2010. Crowley is clearly an exceptional character, who has achieved fantastic things through enormous determination and will power, in addition to considerable ability and skill. But, at a lesser level, there are other examples of patient- or carer-motivated drug development, involving group effort. The Cure Parkinson’s Trust is a leading charity aiming to slow the progression, stop or even to reverse Parkinson Disease, the progressive neurodegenerative condition characterised by rigidity, tremor and bradykinesia. This organisation has rapidly acquired interests into the study of a wide range of potential therapeutic interventions, and is currently connected with over 50 pharmaceutical companies and associated with nearly 3,000 investigators. They are carrying out a number of advanced clinical trials, including a Phase III trial of the calcium L-type blocker isradipine; drug repurposing features frequently in the work they do, with studies underway on exenatide and liraglutide (GLP-1 agonists), simvastatin (HMG-CoA inhibitor) and N-acetyl cysteine (antioxidant). They place a particular emphasis on a network of key opinion leaders with interests in investigating novel mechanisms in the condition, and are led by Dr Richard Wyse, a former lecturer in various London hospitals as well as medical director at two biotech companies. Another example of this phenomenon is Dr Pan Pantziarka of the ReDO project (Repurposing Drugs in Oncology), which was formed from the AntiCancer Fund and Global This organisation has 5 trials underway, mostly drug repurposing combinations such as metformin (antidiabetic)/zoledronate (anti-osteoporosis)/sirolimus (transplant rejection medicine). A particular focus is on the treatment of the rare cancer angiosarcoma with propranolol. Dr Pantziarka has a personal reason for his interest in cancer, but is also scientifically trained. ReDO are looking at putting in place a regime of tax incentives from the UK Government for the development of generic repurposed drugs. These examples point out the complex ways in which charities are becoming integrated into the drug R&D landscape, far beyond their original role in fundraising and care support for their conditions, patients can be medical experts, drug developers and clinical investigators. This is particularly the case for rare diseases, but in the future the changes will almost certainly extend into more common diseases too. For the larger charities, this is not an entirely new phenomenon: Cancer Research UK supports a lot of research activity already – in 2015/6, amounting to £376 million, including nearly £120 million into the biology of cancer. The British Heart Foundation, too, spends over £100 million per annum, mostly on basic research. The focus on drug repurposing as a more efficient translational strategy is likely to grow, however, because of the cost and time advantages which characterise this approach, and it will be interesting to see what changes accrue when some of the larger charities adopt it to the same degree as some of the examples cited above.