Meet the Experts: Rare Diseases with Dr. Joe Clarke

Most of us know someone who suffers from myopia, known as near-sightedness. It means that a person can see things clearly up close, but not at a distance. It is one of the most common reasons for wearing eyeglasses and is an easily managed condition. It might seem an unusual jumping off point for a discussion on rare diseases, but it’s an example that Dr. Joe Clarke gave to illustrate the underlying logic of treating them – identify the abnormality and find a way to manage it. Management in this situation is not a cure, but the treatment—wearing prescription glasses – makes the handicap almost irrelevant.

Rare diseases are much more complex than myopia. They are exceeding expensive to treat, generally starting at $100,000 per year per patient and going as high as $2 million. Patient pools are small (since rare diseases are rare by definition) and it is sometimes a challenge to gather the kind of evidence around treatment options that is usually needed to evaluate potential drugs for effectiveness. A National Rare Disease Strategy would go a long way to address some of these challenges, and we recently spoke with Dr. Clarke, a special advisor to Reformulary Group’s Expert Committee and Professor Emeritus of Pediatrics at the University of Toronto, about his life’s work and the unique challenges in this space.

As a starting point, it’s usually easy to identify the number of patients affected by a well-known condition, but that’s tricky in the world of rare diseases. There is no globally recognized standard definition, and by some estimates there are anywhere from 6,000 to 8,000 individual rare diseases in existence. Some only affect a small handful of patients worldwide, while others affect thousands. The Canadian Organization for Rare Disorders uses the metric of fewer than 1 in 2,000 people affected to define a rare disease, while in the United States, a rare disease is a condition affecting fewer than 200,000 Americans – a definition created by Congress in the Orphan Drug Act of 1983.

Advancements in molecular genetics have allowed us to identify and name rare diseases that were not known to medicine when Dr. Clarke began practicing 55 years ago. In fact, he estimates that up to 95% of rare diseases that we recognize today were not known to exist 50 years ago. The ability to isolate and identify individual mutations affecting metabolic enzymes, cells that are necessary to perform many life-sustaining functions, has dramatically increased the number of rare diseases for which the cause is now understood. The progress in that time period of how some rare diseases can be effectively managed has been remarkable – for instance, Tay-Sachs disease, a condition that causes progressive brain damage resulting in death in early childhood, has been almost eliminated since the 1960’s as a result of the ability to identify parents whose children are at risk for the disease and ways to prevent it. The complications of Gaucher disease, another rare disorder for which the basic cause was discovered 50 years ago, are now almost completely preventable by treatment discovered only 30 years ago.

One of the challenges in treating rare diseases is that the treatment is almost never cost-effective by conventional criteria. But Dr. Clarke feels strongly that the benefit to patients, which can be lifesaving, is often well worth the costs – this view is shared by most provinces. Taking the example of Gaucher disease, much of the initial research to establish what’s known as “proof of principle” (confirmation that something works, in this case enzyme replacement therapy) was funded by the United States’ National Institutes of Health. As the initial research was not borne by manufacturers, there shouldn’t be a need for an eye-popping price tag to recover those costs, but that hasn’t been reflected in the price of treating the disease, which ranges from about $150,000 – $300,000 per patient per year and higher. In fact, the basic research on most rare diseases is funded by governments or academic institutions, while the profits from commercialization is often made by companies that may have invested relatively little in the development of an effective treatment.

Further leadership in developing a national strategy could help relieve some of the pressures in several ways. One continuing problem is the uncertainty surrounding how the pricing of newly development treatments for rare diseases is established. By aligning efforts across the country, not only could Canada move towards fair pricing and increased purchasing power by presenting a united front in negotiations with suppliers, but patients would have greater clarity on what medications might be covered for them and not be subject to some of the inequities that come from the current patchwork, such as coverage varying by where they live.

National leadership could also move the needle on support for research and development of treatments for rare diseases, which is one of the biggest underlying factors behind cost and access. Strategic decisions around supporting research into promising treatments could defray costs to patients and other payers over the long term. A strategy that sets national standards for evidence and funding decisions, as well as tracking patient outcomes and health data, can also serve to provide clarity to both patients and manufacturers as newer medications emerge.

Adequately supporting Canadians affected by rare diseases requires a comprehensive approach with input from government, the pharmaceutical industry and patient groups. Dr. Clarke is buoyed by the fact that over his long career, stakeholders have overwhelmingly wanted to do the right thing and make treatments for rare diseases accessible to more Canadians. As key pieces of the puzzle, like a National Rare Disease Strategy, come to the forefront in the next little while, we know that consultation with appropriate experts will be critical to getting it right.