Seeking Timely Access to Medical Innovation
“The speed at which scientific discoveries are taking place has increased exponentially, and the system was simply not built to adapt to these rapid medical advances” Andrew McFadyen, Executive Director, The Isaac Foundation
By D.F. McCourt
In Canada, our health care system is a point of national pride. The idea that all Canadians should have fair and equal access to the best health care possible is core to our civic identity. Unfortunately, for Canadians with rare diseases, the reality often fails to live up to the ideal.
Though each individual rare disease is—by definition—rare, collectively these conditions affect millions of Canadians. While many rare diseases still lack treatment options, innovation is progressing rapidly and an overwhelming number of families are in urgent need of access to treatments that can be life-changing and even life-saving.
In 2006, Andrew McFadyen’s son Isaac was diagnosed with mucopolysaccharidosis (MPS) VI, a rare and progressive genetic disease. The year prior, the U.S. Food and Drug Administration (FDA) approved an enzyme replacement therapy specifically for MPS VI. Despite the existence of this beneficial treatment, the McFadyens had a lengthy fight in order for Isaac to receive access to it in his home province of Ontario. Realizing that parents had little influence in the political arena where health care access decisions are made, Andrew founded The Isaac Foundation with the mission of helping families affected by rare diseases. “It’s very difficult to get anywhere as patients or parents in the political system,” says Andrew. “An organization has a much more powerful ability to advocate for patients’ needs. Parents and patients should have a voice at the table where the decisions are happening. I also feel that parents should have time to be parents, rather than needing to be full-time advocates.”
Though Isaac was eventually able to gain access to the MPS VI treatment, too many families are still living in limbo. In Halifax, Kim Mason is watching her two sons, Denver and Jaxom, slowly lose their health and independence to Batten disease, a progressive disorder of the nervous system. Until very recently, no treatment for Batten disease existed, but a treatment that was approved by the FDA in 2017 changed everything. “Of course we got excited, and our genetics doctor put in an application to pharmacare here in Nova Scotia to see if our boys would be candidates for treatment,” says Kim. “It was denied. I really don’t know what we’re supposed to do next. It’s a race against time with a disease like this. We’re afraid that by the time the treatment is approved, it may be too late.”
Many Stakeholders, One Goal
It’s only natural in situations like this to look for a villain. It would be easy to blame the government or the drug manufacturers for the plight of the Mason brothers. Through his work with The Isaac Foundation, however, Andrew has become convinced that everyone, really, is fighting on the same team. “No one on any side of the table wants to block access for patients with rare diseases,” he says. “They desperately want to ensure access. But the processes in place can make it very difficult for things to move quickly. The speed at which scientific discoveries are taking place has increased exponentially, and the system was simply not built to adapt to these rapid medical advances.”
These advances come in many forms. Winnipeg-based lawyer Martin Pollock has been living with Gaucher disease, a genetic disease that shares some similar conditions to MPS, for his entire life. Since 2000, he has been receiving bi-weekly intravenous enzyme replacement treatment and it has given him his life back. But now, after over 400 IV treatments, he’s reaching the physical limits of what his body can handle. “There’s only so much my veins can take,” he says. “I’ll take the needles as long as I can, but I’m at the point now where they can no longer use the veins in the back of my arms. I get coldness and numbness in my fingers and hands. It’s not going to be sustainable.”
A newly-developed drug that replaces the intravenous infusion with a twice daily pill now exists, after being approved by the FDA in 2014 and Health Canada in 2017. However, so far only the IV treatment has been approved for reimbursement in Manitoba. “I want to see anyone who has this disease be able to receive the pill early on in their treatment,” says Martin, “so they don’t have to go through what I have.”
Many Stakeholders, One Goal
Five-year-old Jordan McInerney of Barrie has been battling acute lymphocytic leukemia (ALL) since before her first birthday. While her disease is not rare itself, the course it’s taken has placed her in a very distinct patient population needing specialized treatment. First-line treatments, including chemotherapy and bone marrow transplants, failed to halt Jordan’s leukemia. Around this same time, a clinical trial for a new innovative gene therapy was taking place at the Children’s Hospital of Philadelphia. Having exhausted existing treatment options, Jordan’s best chance was participation in this trial. She was fortunately able to enroll and access this new treatment.
Known as chimeric antigen receptor T cell (CAR-T) therapy, the treatment uses genetically engineered variants of Jordan’s own T cells to precisely target and eliminate her specific leukemia. And, for Jordan, it has been working. “Jordan’s life after CAR-T cell therapy has been so much more than we ever dared to hope for,” says Jordan’s father, Stephen. “She spends her time in a kindergarten class instead of a hospital room. She dances, plays with her brothers, and is all smiles and laughter. There was a time when that was only a dream for her. Now she’s living that dream.”
Despite the difficulties involved in travelling back and forth to the U.S., Jordan’s story is one of successful and timely access when it was needed most.
Currently, one CAR-T cell therapy has been approved by Health Canada for pediatric ALL and, once access negotiations are complete, it could open up a new option for children and adolescents whose disease has relapsed or failed to respond to conventional treatments.
With so many new therapies being developed every year, our health care system must adapt in order to ensure Canadians in need have access to these innovative treatments. We must strive for more stories like Jordan’s—stories where the barriers to treatment, if they exist, are manageable rather than insurmountable.
Collaboration is Key
Responding to this need, steps are being taken to develop a new model for access to rare disease treatments. “In 2014, Health Ministers recommended establishing a provincial/territorial Expensive Drugs for Rare Diseases Working Group (EDRD WG),” says Ontario’s Assistant Deputy Minister of Drugs and Devices Division, Suzanne McGurn, one of the driving forces behind the effort. “The working group was asked to explore how to manage access to, and the cost of, drugs for rare diseases with evidence-based approaches.”
Last spring, years of work by the EDRD WG culminated in a new proposed supplemental process to streamline patient access to complex and specialized medications. “The primary objective of this supplemental process is to implement a proactive, consistent, fair, and transparent process,” says McGurn. “Stakeholder feedback is being used to refine the proposal.”
This level of collaboration in action signifies the potential for real change in an area of health care that has been stalled for far too long. It is proof that a new framework for patient access—one that lives up to the Canadian ideals of equal health care access for all—is achievable. We owe it to Isaac, Denver, Jaxom, Martin, Jordan, and the millions of Canadians living similar journeys to turn the potential for change into a reality.
There is no reason our health care system cannot evolve to deliver on its fundamental promises for all Canadians—no matter how common or rare their health issues may be.
Getting a Rare Disease Drug to Market
The cost to develop drugs can be astronomical, especially when a company undertakes research and development in the rare disease space. It’s a risky endeavour, with the failure rate very high. While it’s difficult to pin down the exact dollar figure on what it takes to bring a drug from the lab to market – there are many differing studies showing figures in the billions vs. figures in the hundreds of millions – what we do know is that it’s expensive and very risky. Working together, I’m sure that the pharmaceutical industry and payers can come together to ensure that research, these potential cures and life-saving treatments, can be made available to patients in need in an expeditious, ethical, and equitable fashion. Andrew McFadyen, Executive Director, The Isaac Foundation
Developing a drug in hopes of market approval – through research, clinical trial phases, and the FDA application process – includes a tremendous amount of time, cost, and labour. And there is still no guarantee that a given drug will be approved by the FDA for market.
Further complicating the process, rare disease drugs come with their own set of unique challenges and circumstances, including smaller patient populations, which affect not only clinical trial sizes, but the market potential for a drug post-approval. Moreover, the 1983 Orphan Drug Act dramatically changed the scene in regards to rare disease drug development in the U.S., which is discussed in greater detail below.
Inherently Fickle: Drug Development Statistics
Statistics quoted around pharmaceutical development – including costs, profits, and timelines – are often in dispute. When discussing the overall cost of developing a drug, estimates often roll in the costs of drugs that failed to win approval. Estimates often disregard the cost of capital that is required to begin the Research & Development stage.
Overall statistics and data are just as nuanced as the drug development process itself. For instance, the cost of R&D for an average drug is estimated at $1.4 billion. Yet, successful drugs often cost less than this figure. In addition, there are far more casualties in drug development than there are success stories, affecting this overall average. The odds that a drug in preclinical testing will eventually be approved are 1 in 5,000, and with drugs dying at various stages in the development process – from preclinical, to in-human trials – determining average numbers or statistics is a complicated task.
In the case of rare disease drugs, more orphan drugs are being approved on an annual basis by the FDA. That statistic alone points to the narrative that drug manufacturers are trying to capitalize on the higher price they can charge for these novel treatments and therapies. However, between 2006 and 2010, the approval rates were similar for rare disease and common disease applications (2012), which suggests that it’s science that’s the driving force, our ability to find and treat these diseases is rapidly increasingly, rather than financial considerations driving the innovation.
In terms of costs for rare disease drugs, it is true that most products receiving an orphan approval start out as rare disease treatments, and do not expand their use to non-rare conditions. In essence, these drugs are not being used to treat large sections of the population (FDA, 2017) and the only way to recoup potentially steep R&D costs for companies (including costs for failed attempts at treating a specific disease or family of diseases) is to charge higher costs for these rare drugs.
In the end, the resistance to rare disease drugs, simply because of their price tag, poses a threat to the very development of these drugs that patients are in desperate need of and we implore companies and payers to work together to get these innovative drugs into the hands of patients in need. Whatever the cost of collaboration, our patients are worth it.
By The Numbers – A Glimpse Into the Drug Development Process
$1 Billion USD
The estimated cost to develop an orphan drug. A mass market drug is estimated to cost $2.6 billion. (December 2016 report to U.S. Congress by the Department of Health and Human Services, accessed from NPR, 2017). The 1983 U.S. Orphan Drug Act was created to incentivize companies to develop orphan drugs considered not financially viable, because they treat rare diseases affecting fewer than 200,000 Americans. Those incentives include a waiver on millions of dollars in fees, seven years of market exclusivity, and a tax break for research and development costs.
Using US Centers for Medicaid & Medicare estimates, analysts suggest that orphan drugs represent only 0.5 % of US healthcare spending (Forbes, 2013).
The costs of bringing a drug to market is likely to only increase over time. Eroom’s Law suggests that drug discovery is not only becoming slower, but more expensive, over time. Despite improvements in technology, it’s becoming costlier and more time intensive to bring a drug to market. The trend, first observed in the 1980s, shows that the cost of developing a new drug roughly doubles every 9 years. (More on Eroom’s Law here).
The average time a drug spends in clinical development, though some analysts report that average may be upwards of 12 years (Report to Congress, 2016). This time includes: preclinical testing, using laboratory and animal studies, and safety evaluation (average 3.5 years), Phase 1 Clinical Trial: the first tests of a drug in healthy volunteers (average 1 year), Phase 2 Clinical Trial: larger studies done in patients to testing a drug’s effectiveness (average 2 years), and Phase 3 Clinical Trial: the broader trials submitted to the FDA to obtain drug approval (average 3 years).
$157 Billion USD
The estimated amount the global pharmaceutical industry spent on research and development by private and public companies alone in 2016. (PharmaTech)
600 and 1 in 5000
The number of new drugs that have received FDA approval to treat rare diseases since the 1983 Orphan Drug Act was introduced. In the decade before the passage of the Orphan Drug Act, which was created to incentivize drug developers to treat rare diseases, only 10 industry products for rare diseases were brought to market. 2017 saw over 50 drug approvals (as of September 2017), compared to just 2 in 1983 (FDA, 2017). As dramatic, the chance for a new drug to actually make it to market is 1 in 500. Estimates suggest only 5 in 5000 drugs that enter preclinical testing will progress to human testing. One of these 5 drugs tested in humans is approved (Medicinenet).
More Information – Important Resources
Reimbursement of Treatments for Rare Diseases in Canada – A Long and Arduous Process
From an access standpoint, there is no reason for delay, and no reason why patients who need access can’t receive it soon after regulatory approval from Health Canada. Patients suffering from these rare and progressive diseases don’t have the luxury of time on their side, and the current process is long and arduous. Companies and governments can and should help patients now while these processes play out, and I remain hopeful that true collaboration with all stakeholders can take place. Andrew McFadyen, Executive Director, The Isaac Foundation
If a drug receives a positive recommendation, the file then moves to the pCPA (Pan-Canadian Pharmaceutical Alliance) for bulk pricing negotiations. In this stage, negotiators assigned to represent all prices open discussions with the company in an attempt to come to terms on the cost. Because rare disease drugs are often some of the most expensive in the world, these negotiations take a very long time – anywhere from 6-18 months. If negotiations result in a deal, provinces can then decide to accept the deal and begin delivering the drug to patients on their drug plan. Occasionally, no deal is able to be struck between pCPA and the company, and the drug remains difficult or impossible to secure for patients in need.
While these processes undergo their reviews, Physicians with patients suffering from a rare disease may fill out a request for reimbursement application and submit it to the provincial Ministry of Health. From there, the application is reviewed and a decision to cover the cost of treatment is either approved or, in most cases, denied. Most reasons governments provide for denial are due to a lack of evidence of the benefits these treatments provide patients, especially while the CADTH reviews are in place. In many provinces, policies are in place that prevent these decisions from being rendered until the above reviews have been completed. Companies can work directly with governments to see how drugs can be accessed while reviews are taking place, and they are often encouraged to show a willingness to help provide access for their patient population by drugs on a compassionate use basis.
Bureaucratic Path to Reimbursement – Information and Estimated Timelines
Bureaucratic Path to Reimbursement Could Take 18-24 Months Longer
STEP 1 - Approval By Health Canada
A company submits their drug to Health Canada for review and approval for use in Canada. Many reviews for rare disease drugs are considered a “priority” review because of the potential impact the therapy could have on patients.
STEP 2 - Submission and Review to the Common Drug Review (CDR)
The Common Drug Review is a “process for conducting objective, rigorous reviews of the clinical, cost-effectiveness, and patient evidence for drugs.” The CDR completes their review and recommends to provinces whether a drug should be reimbursed or not.
STEP 3 - Negotiations Begin With the Pan-Canadian Pricing Alliance (pCPA)
The Pan-Canadian Pricing Alliance works to capitalize “on the combined ‘buying power’ of drug plans across multiple provinces and territories” to bring the cost of expensive treatments down. If a drug receives a recommendation at CDR to continue to the pCPA negotiation process, negotiations could take 12-18 months.