This chapter provides an overview of Health Canada’s proposed orphan drug framework, reviews some innovations in the treatment of rare diseases, and addresses strengths of and challenges facing Canadian research on rare diseases. The chapter concludes with the Committee’s observations and recommendations to support innovation in research and treatment for rare diseases.

A. Rare Diseases in Canada[142]

Rare diseases are defined as diseases that affect less than one in 2000 individuals worldwide.[143] A specific rare disease may affect fewer than 12 people in Canada. Despite the low prevalence of individual rare diseases, however, because approximately 7,000 rare diseases have been identified, many Canadians are living with rare diseases. It is estimated that 1 in 12 Canadians has been diagnosed with a rare disease. Rare diseases are often serious chronic conditions that may be debilitating or even life-threatening. Many have very early onset and can be diagnosed in childhood. About 80% of rare diseases have a genetic basis.[144]

Rare diseases present challenges to patients, clinicians and researchers that are distinct from those associated with more common illnesses. From the patient’s perspective, people living with rare diseases usually do not have access to the resources of charities, associations and support groups available to individuals living with common diseases. Patients may also experience years of misdiagnosis and social isolation.[145] Many clinicians including family physicians and paediatricians may not be sufficiently familiar with rare diseases to be able to diagnose them.[146] For researchers, the small population size makes conducting clinical trials of potential treatments very difficult.

The drugs that are used to treat rare diseases are referred to as “orphan drugs.” Currently, there is no approval process for orphan drugs in Canada, so physicians face challenges in obtaining these drugs for patients. Health Canada announced on 3 October 2012, however, that it is developing a modern framework for orphan drugs in Canada.

B. Canada’s Proposed Orphan Drug Framework

Mr. David Lee of Health Canada’s Office of Legislative and Regulatory Modernization, Policy, Planning and International Affairs Directorate explained Health Canada’s forthcoming orphan drug framework to the Committee.[147] The framework was specifically designed with the knowledge that rare diseases have “small, vulnerable patient populations.” The framework is intended to allow Health Canada greater flexibility in the approval of orphan drugs, given the challenges associated with rare disease research.

First, the framework will align Canada’s drug regulations with those established in the United States and Europe, which is intended to help scientists pool resources in rare disease research and treatment. Reduced regulatory barriers are also expected to facilitate international collaboration and enable increased innovation. Second, the framework will allow for increased post-market surveillance of orphan drugs to ensure their safety and effectiveness. Third, the framework will allow for patient input into the decision-making process. Most importantly, the proposed framework is intended to increase access to drug treatments for rare diseases. Mr. Lee reported that the Department would soon be engaging in public consultation on the framework and would incorporate feedback into the final framework proposal.

Each witness who appeared before the Committee to discuss rare diseases expressed strong support for the proposed orphan drug framework.

C. Innovations in the Treatment of Rare Diseases

At the same time that Health Canada announced its proposed orphan drug framework, it announced that the CIHR would fund Canada’s participation in Orphanet, an international reference portal focused on rare diseases.[148] Dr. Micheil Innes, National Coordinator of Orphanet Canada explained to the Committee the innovation that Orphanet brings to the rare diseases community in Canada. Orphanet provides comprehensive information on rare diseases and is accessed over 20,000 times daily. The Canadian portal provides rare disease information in French and English, including an inventory of orphan drugs and a directory of services such as clinics, laboratories, research projects, registries and family support groups where available. Dr. Innes told the Committee that Orphanet can also be a particularly useful tool for primary care physicians who may not be familiar with rare diseases.

Dr. Innes also spoke more broadly about how advances in genetic technologies will lead to increased access and faster diagnosis for individuals with rare diseases.[149] For example, he explained that currently testing for one gene of the approximately 22,000 genes in the human genome costs between $1,000 and $3,000. However, individuals with rare diseases have to undergo multiple genetic tests to identify which specific gene they might have in order to determine which condition they have, which could cost in excess of $10,000. There are currently about 2,500 genes for which there are tests and of these, about 150 tests are available in Canada. Now with advances in new technology and next generation genome sequencing, which were described in chapter 3, it is possible to sequence the entire genetic code, which is the equivalent of having approximately 22,000 genes tested at once, at a cost ranging from $2,000-$3,000 for research purposes[150] to $5,000.[151]

Ms. Jacquie Micallef with the Neurological Health Charities Canada described an innovation that has been used to enable communication for non-verbal individuals.[152] She used the example of Rett syndrome, which is associated with certain physical and cognitive impairments, including an inability to speak. Ms. Micallef described a communication device based on eye gaze technology, which enabled a 25-year old woman, previously assumed to have the cognitive capacity of a six-month-old, to communicate preferences to her mother. For this woman and others living with similar challenges, this technology can contribute to greater autonomy and a better quality of life. Ms. Micallef reported that the technology was validated in a study of 100 individuals and has been used for children as young as three years of age.

In a brief submitted to the Committee, Mr. Darren Bidulka, President of the Canadian Fabry Association, described innovations that affect people suffering from Fabry disease.[153] Fabry disease is a rare condition that affects an estimated 362 known individuals in Canada. Without treatment, the disease leads to heart and kidney failure in early middle age, as well as strokes and other complications. Mr. Bidulka explained that the most recent innovations in Fabry treatment have led to enzyme replacement therapy, which addresses many of the complications associated with the disease. However, he suggested that additional innovations are needed as the treatment does not appear to address the risk of stroke and the enzyme replacement therapy requires intravenous treatment every two weeks.

D. Strengths of and Challenges Facing Rare Disease Research and Treatment in Canada

The Committee heard from Dr. Durhane Wong-Reiger that Canada is a leader in genetic research, and given that 80% of rare diseases have a genetic basis, Canada is well-placed to make significant contributions to rare disease research.[154] She noted, however, that while Canada contributes heavily to our understanding of the mechanisms underlying rare diseases, especially through CIHR and Genome Canada, Canada is behind other nations in developing treatments and screening tests, particularly for newborns.

The Committee heard that that the rare disease community is one that relies on international collaboration, in part out of necessity because of the small patient populations, and in part because the small number of clinicians who specialize in a particular disorder often know each other.[155] Mr. David Lee suggested that the proposed orphan drug framework would be responsive to new developments in other countries, with safety data flowing from international sources, and consistency in regulations across international jurisdictions. Dr. Wong-Reiger noted that because of Canada’s ethnic diversity and its “pockets of geographic isolation,” a particular rare disease may be overrepresented, making Canada an ideal place to conduct rare disease clinical trials.

As Dr. Micheil Innes of Orphanet Canada explained to the Committee, one of the most difficult challenges for people living with rare diseases is getting a diagnosis; in fact, estimates suggest that over 50% of individuals with rare diseases do not have a correct diagnosis of their condition. Dr. Innes added that beyond the challenges of diagnosis, only about 200 therapies have been developed for thousands of rare diseases.

Both Ms. Micallef of the Neurological Health Charities Canada and Dr. Innes of Orphanet expressed concern about some of the social effects that advances in genetic testing might have on individuals found to have a genetic predisposition to certain rare disorders. Specifically, they expressed concern that given the increased availability of genetic testing, individuals found to have certain genetic differences might experience discrimination on that basis.

E. Committee Observations and Recommendations

The Committee heard that Health Canada has recently taken valuable steps toward increasing our understanding of rare diseases and increasing access to treatments for individuals living with rare diseases. It heard that Canadian researchers are international leaders in some areas of research of particular importance to rare diseases, but that more innovation is needed in the areas of screening and treatment. Given the importance of diagnosis to individuals living with rare diseases, the Committee believes that innovation in this area must be fostered.

Reflecting these findings, the Committee therefore recommends that:

14. Health Canada, in addition to its support of Orphanet, participate in and contribute to international rare disease registries to facilitate international cooperation on the treatment of rare diseases.

15. Canadian Institutes for Health Research and the Public Health Agency of Canada, in collaboration with the Networks of Centres of Excellence, consider identifying clusters of rare disease research in Canada, and consider formalizing some of them as Centres of Excellence within the Network.

16. Health Canada consider whether it is necessary to establish a framework for non-pharmaceutical treatments such as medical devices used to treat rare diseases in the orphan drug framework or whether it is necessary to create a parallel framework for non-pharmaceutical treatments.