John Bell is a senior scientist at the Ottawa Hospital Research Institute and a professor of medicine at the University of Ottawa. Alex MacKenzie is a pediatrician at CHEO and a professor of pediatrics at the University of Ottawa.
There exist as many as 10,000 rare diseases affecting approximately one million Canadians, more than half of whom are children. Rare diseases are often serious disorders, affecting one-third of pediatric hospital in-patients and accounting for one-third of all deaths in the first year of life in Canada. Given that they affect the very young, the number of life years lost due to rare diseases is greater than those attributed to infectious disease and diabetes combined. And sadly, therapies are available for fewer than 5 per cent of children with a rare-disease diagnosis.
The federal government recently announced $1.4-billion in funding to treat rare diseases. On the surface, this would seem to be a cause for optimism since the significant majority of rare diseases are caused by genetic mutations – entities that are becoming increasingly treatable.
Genetic mutations are either inherited or spontaneously occurring typographical errors in our DNA. Fortunately, the process of DNA sequencing has been declining in cost and increasing in speed. In combination with significant improvements in our ability to correct these genetic typos – either by “genome editing” or by introducing normal, unmutated DNA that the body can copy – the diagnosis and successful treatment of those affected by rare diseases is becoming increasingly possible.
One example is spinal muscular atrophy, or SMA – a pediatric ALS-like condition and the most common inherited cause of infant mortality. Most Canadian newborns are now screened at birth for SMA and a single dose of the gene therapy Zolgensma may be all that’s needed to replace early SMA death with what appears to be healthy life. However, the drug currently costs $2.8-million for one dose, making it, until recently, the most expensive drug in the world before its price was overtaken by the gene therapy costs for another rare disease – hemophilia. The arithmetic is not comforting: there exist a dozen – soon to be many dozens, ultimately hundreds – of similar therapies for severe rare diseases, all clinically promising and all unspeakably costly.
The government’s decision to pay pharmaceutical companies for these therapies is understandable given the demands for action from families of patients. But however welcome the new money, this is a reactive short-term solution at best, placing a very expensive bandage on a problem that’s only destined to grow. The prices for current gene therapies are extreme and certainly not sustainable within the Canadian health care system. It is true that rare-disease gene therapies cost a lot to develop and produce, but it is also clear that the sticker price is far higher than it needs to be, as it’s driven by returns to shareholders. The pharmaceutical industry’s current model of drug development and pricing is more appropriate when consumers number in the tens of millions as opposed to hundreds or even fewer.
Therefore, it is critical to augment the new money with an equal, forward-thinking, pro-active investment in Canadian science and infrastructure, to configure a lower-cost genomic therapy program yielding sustainable long-term solutions for Canadian children and families affected by rare diseases. A number of such undertakings are currently under way in Europe and the U.S., with initiatives involving academics, government labs and enlightened biotechnology companies. While the two-year-old Canadian Biomanufacturing and Life Sciences Strategy is an important first step in this direction, there is more that can and should be done.
Although these treatments will never be straightforward, the declining cost of DNA sequencing and our increasing ability to edit the genome, as well as target different organs and tissues, are wholly compatible with less costly and effective interventions.
For example, a class of DNA-related medications known as antisense oligonucleotides can be generated for a fraction of the cost of more traditional gene-therapy drugs. In addition, the infrastructure needed for such an initiative can be rapidly repurposed for mRNA vaccine generation when – not if – the next pandemic spillover event occurs.
Ultimately our increasingly sophisticated understanding of the human genome, when married to new means of genome editing, will have impacts that extend well beyond rare diseases. Common chronic conditions, including Type 2 diabetes, heart disease, and obesity, all of which disproportionally affect the disadvantaged in society, are candidates for effective one-time therapies if we can control prices.
What we need is consistent, visionary research funding to build the next generation of medicines – an initiative that will benefit all Canadians.