Rethinking Rare: A Call for Innovation and Advocacy

Imagine having a life-threatening disease that only one in a million people worldwide understand or study. For patients with rare diseases, finding effective treatments can feel like a race against time, with limited research, delayed diagnoses, and high costs of development standing in the way. When I worked in a phase III clinical trial testing a novel therapeutic for paroxysmal nocturnal hemoglobinuria (PNH), I came to understand the unique challenges and the critical need for innovation and advocacy in rare disease drug development.

For any new drug to reach patients, it must demonstrate both efficacy and safety through a rigorous progression of in-vitro studies, animal testing, and clinical trials across three major phases. On average, these steps take a decade or more, cost billions of dollars, and yet over 90% of drugs never make it to the market. For rare diseases, these challenges intensify due to the small patient population and limited clinical data, which often require studies to be conducted internationally. Additionally, rare diseases frequently require extended Phase IV trials, further delaying market entry and shrinking profit-earning years for an already small market potential. The high cost and low financial return on investment make it challenging for companies and investors to support rare disease drug development.

To help offset these hurdles, some countries provide support through orphan drug designation which includes measures that make drug development far more feasible. With this status, companies gain access to specialized grants, tax credits, fee waivers for applications (which can reach up to $3 million), closer collaboration with regulatory bodies, and 5 to 10 years of market exclusivity. While the U.S., Europe, Japan, and other nations have orphan drug programs, Canada does not. As a result, the estimated 1 in 12 Canadians affected by rare diseases, often experience delayed access to these essential treatments.

Canada's approach to drug pricing presents further challenges. The Patented Medicines Price Review Board (PMPRB) controls drug pricing in Canada but does not provide a separate framework for pricing orphan drugs. Unlike drugs for more common conditions, orphan drugs are typically priced higher to offset the high research and development costs in relation to a smaller market size and limited competition. For example, PNH treatments can cost as much as half a million dollars per year. As a result, patients who aren’t eligible for support programs due to limited availability must rely on blood transfusions just to survive. Moreover, because rare disease drugs typically lack generic counterparts, this monopoly on the rare disease market further inflates prices.

While lowering drug costs is essential to expanding patient access, the absence of an orphan drug framework and competitive incentives in Canada creates an environment that both restricts new treatments from emerging and monopolizes the market for those that exist. This lack of market incentives diminishes the attractiveness of Canada’s rare disease drug landscape and, in turn, limits treatment options for Canadian patients.

So, why focus on rare disease research at all? Rare diseases are often linked to genetic pathways shared by more common illnesses, allowing us to uncover mechanisms underlying multiple disorders. For instance, the defect in glycosylphosphatidylinositol anchor formation seen in PNH also appears in specific seizure types, cardiomyopathies, and intellectual disabilities. The limited competition in this field also leaves ample room for innovation. Beyond these scientific opportunities, advancing rare disease research raises awareness within the medical community, which can shorten diagnostic timelines and improve patient outcomes. Living with a rare disease is often isolating, as even healthcare professionals may lack understanding. It can take up to five years to diagnose a PNH patient, during which patients undergo multiple emergency departments visits, severe fatigue, and ongoing organ damage from hemolysis. With increased research, we can enhance awareness, reduce diagnostic delays, and connect patients with the care they urgently need.

We have made significant strides in supporting biotechnology innovation and safeguarding patient safety. But to truly ensure treatment accessibility, Canada must reconsider how it supports orphan drug development and its pricing policies. As medical students and future healthcare providers, we can push for more research and policy changes to encourage innovation and make treatments accessible to all. It is our duty to ensure that patients with rare diseases are not left behind in the innovation of new therapies.