Personalized medicine is defined as treatment tailored to one or a few patients with life-threatening diseases, for example cancer that no longer responds to chemotherapy or an infection resistant to several antibiotics.
Although personalized medicine is promising, it is labor intensive and costly, and regulatory approval and reimbursement procedures are complex. This is because the development of clinical trials is limited by the small number of eligible patients.
Drawing on recent examples of chimeric antigen receptor T cell (CAR-T) therapy for recurrent cancers, and phage therapy for antibiotic-resistant bacterial infections, we will illustrate how Canadians could benefit from these solutions. personalized.
Challenges include ensuring equitable access and determining who should cover the cost of these important medical advances.
CAR-T therapy for recurrent cancers after chemotherapy
CAR-T therapy was first approved in 2017. In this treatment, the patient’s white blood cells are collected and modified in the laboratory to better identify and destroy the specific tumor. The modified cells are then injected back into the patient, where they attack the cancer.
CAR-T therapy shows great promise for certain types of advanced leukemia or lymphoma. Many patients achieve remission after treatment, and some even achieve long-term recovery.
For example, the first CAR-T therapy has already achieved a remission of more than 80% three months after treatment and 62% two years later. Emily Whitehead, the first pediatric patient to receive CAR-T cells, still has no signs of cancer, 12 years after her treatment in 2012, when her life expectancy before therapy was only a few weeks.
Phage therapy for antibiotic-resistant superbugs
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Another treatment adapted to the patient is based on the use of phages, these viruses which kill bacteria, but which are harmless to humans and animals. They were discovered more than a century ago by the French-Canadian microbiologist, Félix d’Hérelle; It was used to treat infections before the discovery of antibiotics.
With rates of antibiotic resistance increasing worldwide, people are once again turning to phages to treat otherwise untreatable “superbug” infections.
Phages are finicky, so it is necessary to associate them with prey that they can recognize among the bacteria causing the infection. Several types of phages are generally combined in a “cocktail”, to reduce the risk of the bacteria escaping their detection.
In 2023, the first modern Canadian trial of phage therapy to treat a drug-resistant UTI proved to be a success. The patient had already lost a kidney as a result of this infection, which antibiotics alone were unable to cure.
In another recent example, a man suffering from a complex infection in his artificial hip was successfully treated using phage therapy.
Many issues
Personalized medicine is expensive. This is partly explained by the complexity inherent in the design of adapted therapies and by the constraints linked to individualization which restrict the possibility of achieving economies of scale likely to lower costs. Production methods could be standardized to a certain extent, but there will always be characteristics specific to each patient.
For example, although phages are abundant and easy to find in nature, matching the right phages to a patient’s superbug requires a lot of time and effort. Few manufacturers are able to prepare clinical-grade phage cocktails in a very short time if conventional antibiotic treatments fail.
-In the case of CAR-T therapy, the patient’s cells must be taken and modified to target their specific tumor. This process requires rigorous quality control, advanced training and equipment, and a single infusion can cost more than US$350,000. Pre- and post-treatment expenses can bring the actual price to more than US$1 million. This high price places a heavy burden on the health system and constitutes a major obstacle to access to treatment.
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New manufacturing methods
To reduce costs associated with third-party production abroad, Canadian researchers have begun testing new methods of manufacturing CAR-T therapies directly at Canadian academic institutions.
Health Canada’s standardized regulatory approach to drugs was designed for the approval of a single treatment for many patients, based on data from large clinical trials. Personalized medicine, for its part, requires a new model that makes it possible to approve individualized treatments for a much smaller group, or even for a single person.
Therapies intended for small groups of patients can be evaluated under Health Canada’s new Notice of Compliance with Conditions (NOC-C) procedure, which allows promising treatments to benefit from conditional market access. Full authorization at a later date is dependent on the collection of additional clinical evidence.
This approach accelerates the approval process so that Canadians can more quickly access treatments for life-threatening or debilitating illnesses. Further changes to regulatory processes may be necessary to accommodate the increase in personalized medicines.
The example of Belgium
Another solution for Canada would be to follow the example of Belgium, which decided to pre-approve a large quantity of individual phages, which could then be combined differently for each patient without further regulatory formality. Belgium recently released data on the first 100 cases, reporting high success rates.
The small sample sizes and lack of standardization of personalized medicine can complicate assessments of its health economic effects that governments traditionally rely on to make approval and reimbursement decisions.
Canada has begun to optimize data and real-world evidence from clinical databases in cases where large-scale trials are not feasible. This information includes patient or health care delivery data that is already collected regularly from a variety of sources, including electronic health records or digital health technologies.
Strategies to improve access
However, there remain obstacles to overcome in the collection and integration of information in our various provincial health systems. The Canadian government recently invested $20M to improve the collection and use of real-world evidence for regulatory decision-making as part of a strategy to improve access to drugs for rare diseases , another example where the number of patients is low, but the effects of the disease are significant.
New methods for assessing the cost-effectiveness of personalized medicine will also be essential. These methods make it possible to determine the cost of a treatment based on the prevalence of the disease, the accuracy of diagnostic tests, its effectiveness, the likelihood of complications, the availability of better therapeutic solutions and the number of years of life adjusted for quality of life. Having a clearer idea of the cost-economics of personalized medicine will make it easier to justify the need to use limited healthcare resources.
Implementing an outcomes-based reimbursement model could also address cost, reimbursement, and access issues. In this case, payments would only be made if the patient responds to treatment within a certain time frame. Patient assistance programs will also be instrumental in offsetting some of the costs. They are sometimes offered by pharmaceutical companies to provide prescription drugs to eligible individuals at a low cost or even for free.
With the emergence of new solutions for a growing number of pathologies, the field of personalized medicine will continue to grow. Ensuring rapid and affordable access to these therapies will be of utmost importance, given their high cost and small patient populations. To achieve this, collaboration between pharmaceutical companies, government agencies, insurance companies and health care institutions will be essential.
