Submitted to Suzanne McGurn, President and CEO, Canadian Agency for Drugs and Technologies in Health (CADTH), and Minister of Health, Mark Holland
November 30, 2023
Suzanne McGurn
President and CEO
Canadian Agency for Drugs and Technologies in Health (CADTH)
865 Carling Ave., Suite 600
Ottawa, ON, Canada, K1S 5S8
Dear Ms. McGurn,
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive, terminal motor neuron disease affecting
approximately 3,000 Canadians and their loved ones. ALS does not discriminate, anyone can receive a
diagnosis of ALS regardless of age, gender, socioeconomic status, geography or race. The disease can
move with startling swiftness, causing progressive paralysis. On average over a two-to-five-year period a
person living with ALS will lose the ability to walk, talk, eat, move, swallow and finally, to breathe.
Receiving an ALS diagnosis is devastating and the disease’s physical, emotional and financial impact on a
person and their family are immense. Yet the unique and complex care needs of Canadians living with
ALS continue to go unmet, especially as it relates to access to treatments under public drug plans.
Health Canada’s approval of two therapies for the treatment of ALS in 2022 was an important and
hopeful milestone for people living with ALS. Yet this moment was quickly overshadowed by the reality
that Canadians living with ALS do not have immediate access and many may never have access to the
approved therapies through publicly funded drug programs.
CADTH’s current use of highly restrictive clinical inclusion criteria as the basis for its reimbursement
decisions overlooks the heterogeneity of ALS and creates an environment of inequity where Canadians
living with ALS are excluded from having access to safe and effective drug treatments. Furthermore, due
to the restrictive eligibility criteria recommended by CADTH, thousands of Canadians will die of ALS
without being able to access new drugs which could affect the course of their disease and prolong their
lives.
Several promising drug therapies for ALS are currently in the pharmaceutical development pipeline, any
one of which could prove effective and become standard of care. As such, it is expected that the number
of drugs submitted to Health Canada for the treatment of ALS will continue to increase in the near
future.
With this influx of potential therapies, it is imperative that CADTH’s reimbursement review process is
conducted in a way that responds to the needs of a population with a rare disease and limited
therapeutic options. The considerations are different and should be reflective of the need for timely and
equitable access to the treatments they desperately need now and in the future. This would include
broader access criteria that are flexible enough to accommodate new evidence and consider the unique
scientific and clinical issues in the diagnosis and treatment of ALS as it is both essential and urgent to
ensure equitable access to provincially funded ALS therapies for all Canadians who may benefit from
treatment with a Health Canada approved drug.
That is why we are calling on CADTH to work alongside ALS clinicians and the community, to pave the
way for current and future therapies by creating a framework that will address the restrictive and clinically inappropriate eligibility criteria that are currently resulting from CADTH’s reviews, to ensure
people living with ALS have equitable and timely access to new therapies once they are approved.
ALS Therapies: Two Case Studies in Inequitable Access (Albrioza and Radicava)
As an example, the negative effects of aligning reimbursement and clinical inclusion criteria are
exemplified by CADTH’s review of Albrioza, which received a Notice of Compliance with Conditions
(NOC/c) from Health Canada in June 2022.
Even though Health Canada did not impose any restrictions on the patients’ time of diagnosis and
symptom onset for its use for the treatment of ALS, CADTH’s reimbursement criteria for Albrioza
recommended that only people who have had ALS symptoms for less than 18 months and have a
diagnosis of definite ALS (according to El Escorial criteria), as well as meet other restrictive diagnostic
criteria, should be eligible for reimbursement of drug costs under the publicly funded provincial plans.
ALS is a heterogeneous disease, meaning the disease varies from person to person, including where
symptoms first appear in the body, age of onset and rate of disease progression. It can affect different
areas of the body at different rates, meaning that someone with ALS may have significant paralysis in
one body part while maintaining function in another.
In Canada, it takes up to 20 months from first symptom on average for an individual to be diagnosed
with ALS1. As there are no confirmed biomarkers for the disease, current methods for diagnosing ALS
involve ruling out other diseases that share similar symptoms, which is often a long process. The
timelines to get referred to an ALS specialist varies by province and territory depending on the
availability of appropriate specialists and testing facilities, or systematic issues within healthcare
systems, including the lack of timely and available healthcare for rural and Indigenous populations.
In addition, at its early stages, ALS symptoms may be associated with only one body part, may go
unrecognized or even attributed to other causes. Alternatively, people may be diagnosed with ALS, yet
experience slow progression of the disease with longer intervals between symptom onset in additional
areas of their body – these may be the individuals who would stand to benefit most from therapies that
slow symptom onset.
The heterogeneity of the disease means that time since symptom onset and the requirement for a
‘definite’ ALS diagnosis are inaccurate and invalid measures of a person’s functional state and capacity
for response to effective drug treatment. Failure to meet these criteria, as proposed by CADTH, does
therefore not preclude a person’s ability to respond to an effective drug.
In fact, it has been demonstrated that CADTH’s restrictive criteria – which are not grounded in the
reality of living with ALS in Canada – will result in less than 10% of Canadians with a confirmed
diagnosis of ALS being able to access Albrioza through public drug plans2
.
CADTH’s current criteria do not account for the lengthy and complicated diagnosis process. In addition,
it fails to recognize the heterogeneity of the disease and creates an environment where people who
have slow progression of the disease with longer intervals from symptom onset to diagnosis will not be
eligible to access this therapy.
1 https://pubmed.ncbi.nlm.nih.gov/30430962/
2 https://onlinelibrary.wiley.com/doi/abs/10.1002/mus.27723
Furthermore, CADTH’s clinical experts advised CADTH that there is no evidence that people with ALS
outside the clinical trial criteria would not respond to the drug treatment. The CADTH clinical expert
noted that “all patients diagnosed with ALS would be suitable for treatment with PB-TURSO” – a
statement supported by the Canadian ALS Research Network (CALS) in their clinical group input.
Albrioza is not the only ALS therapy to face restrictive access due to reimbursement criteria that do not
align with the reality of diagnosis and treatment of ALS in Canada. In March 2019 CADTH published
reimbursement recommendations for the intravenous formulation of Radicava (edaravone), the second
ALS therapy to be approved in Canada – and the first in approximately 20 years. The reimbursement
criteria outlined in the recommendations restricted eligibility based on patients’ scores on individual
items on the revised ALS Functional Rating Scale (ALSFRS-R).
Specifically, patients who have functional impairment in a single domain and score less than 2 on a
single item on the ALSFRS-R, but are otherwise adequately functional, are precluded from access to
Radicava under provincial drug benefit plans. These eligibility criteria were once again reflected in the
reimbursement recommendations published in January 2023 for the oral formulation of Radicava
(edaravone).
As an example of the invalidity of this approach, a patient who can be fully functional with regard to
such activities as speech, swallowing, ambulation and dressing, but may require help with cutting food.
would have a score of less than 2 on that item of the ALSFRS-R, leading to ineligibility for reimbursement
under provincial drug benefit programs.
Moreover, as our understanding of ALS has evolved, so has the clinical approach to diagnosis, treatment
and care. As such, the ALS community, including clinicians, has been vocal about the ALSFRS-R not being
an ideal way to measure disease progression due to the heterogeneity of the disease. Yet, there has
been no commensurate evolution in CADTH’s approach to setting eligibility criteria.
When considering these factors, it is evident that reimbursement criteria based on time since symptom
onset, restrictive El Escorial definitions and individual ALSFRS-R scores places restrictions on drug access
that are unjustifiable, scientifically, clinically and ethically. These criteria do not reflect the real-world
experiences of people living with ALS in Canada, and their implementation further reinforces the
inequality within our healthcare system.
Real World Evidence and the barriers to generating it
We know that in recent years the implementation of Real World Evidence (RWE) has become an
important area of focus for regulatory and reimbursement decision-making bodies such as CADTH.
Especially for rare diseases like ALS, RWE is a critical aspect of evaluating a therapy’s use, safety and
effectiveness given the various challenges experienced by researchers during clinical trial stages (i.e.,
smaller sample sizes, poor survival rates, etc.).
By collecting RWE, we can expand our knowledge of patient outcomes and develop our understanding
of available treatment options. A prerequisite for understanding how patients respond to drug therapies
and their impact on their day-to-day lives is having patients being able to access these therapies.
However, given the current restrictive eligibility criteria for ALS drug therapies, collecting RWE that
will expand our insights in the disease will not be possible in Canada.
Without the ability to collect RWE for a broader group of patients, there will be a negative effect on our
understanding of the disease, the usage and potential benefits or risks of ALS drug therapies. CADTH must consider expanding eligibility criteria beyond that of clinical trial inclusion criteria for ALS drugs or
risk the ability to collect vital RWE.
In Summary
ALS is a heterogeneous disease in which symptoms and signs, rate of progression and life expectancy of
individuals vary significantly, a reality that must be taken into consideration when considering criteria
for drug reimbursement.
No one should lose their life while waiting to see if a newly approved treatment will be covered by the
provincial formulary. As shown above, inequity of access to drug therapies further perpetuates the
various challenges that Canadians living with ALS face and creates significant barriers to opportunities to
improve our understanding of the disease.
We are requesting that CADTH demonstrate commitment to equitable and timely access to ALS
therapies for Canadians by working with the ALS clinical and patient community to amend the current
practice of using only clinical trial inclusion criteria for reimbursement recommendations. A
framework must be put in place that establishes reimbursement criteria based on the clinical
expertise of ALS neurologists.
If changes are not made immediately within the CADTH process, thousands more Canadians will die
without access to life-prolonging drug treatments because they could not access health services in time
to meet the restrictive criteria set by CADTH.
Now is the time for CADTH to eliminate the barriers preventing Canadians living with ALS from having
timely, equitable and affordable access to the drugs they need.
Our organizations are committed to equitable access to treatments for people living with ALS. We would
like to meet with you and your scientific staff to discuss how the approach being used by CADTH to
evaluate therapies for ALS can be better aligned with the clinical realities of diagnosis, treatment and
with our current understanding of the neuropathology of this disease as discussed in a recent
publication in the Canadian Journal of Neurological Sciences (attached).
Thank you for your consideration.
Sincerely,
Tammy Moore, CEO, ALS Society of Canada
Jida El Hajjar, Executive Director, ALS Action Canada
CC: The Honourable Mark Holland, Minister of Health
CC: Michèle de Guise, Présidente-Directrice Générale de l’Institut national d’excellence en santé et en services sociaux (INESSS)