ALS Action Canada Position Paper
| Executive Summary |
For 100+ years, thousands and thousands of people diagnosed with Amyotrophic Lateral Sclerosis (ALS) were sent home by their doctors to die a horrific death because there were no meaningful treatments available. This represents an ongoing health crisis in Canada and around the world; a health crisis that has become more acute during the COVID-19 pandemic.
ALS patients across Canada are genuinely and deeply grateful for those who have dedicated their lives and resources to caring for the ALS community. In recent years, the ALS story has changed. It is no longer just about wheelchairs and medically-assisted dying. It now includes unprecedented hope given that there are over 160 drug companies working on ALS projects; there are several promising ALS therapies in the late stages of the clinical trial pipeline; there is a Phase 3 clinical trial therapy that appears to be stopping the progression of a certain type of genetic ALS; there are new, innovative clinical trial formats and new, bold, patient-led advocacy organizations are demanding action, not just awareness. The reality, however, is that all of this activity has been largely happening outside of Canada.
Canadian patients are faced with a crisis of hope. Despite the prospect of scientific breakthroughs, the current Canadian drug approval process is longer than the expected lifespan of an ALS patient. In other words, if a scientifically validated cure is made available in the USA tomorrow, and a Canadian is diagnosed with ALS the following week, that Canadian may not survive to access the therapy. They will most certainly have to pay for it and if they cannot afford the therapy, they, in all probability, will die before provincial coverage is made available. Canadians are fighting for the right to live.
As such, ALS patients have formed ALS/SLAAction Canada to establish a patient-led advocacy movement that is committed to ensuring that the new ALS story of unprecedented hope is heard and that urgent action is taken to save the lives of thousands of innocent Canadians. ALS/SLA Action Canada is respectfully requesting that our federal and provincial governments, with the assistance of corporate partners and private donors, implement our 15 recommendations in order to end the ALS Crisis and save our lives.
Our 15 recommendations are grouped into the following categories:
1. Ensure immediate access to promising therapies once approved in other countries.
2. Ensure immediate provincial health care plan coverage for new ALS therapies.
3. Bring more, and better designed, clinical trials to Canada for ALS, that reflect the timely progression and fatality of the disease.
4. Increase the funding of ALS research.
The Canadian government has mobilized quickly and capably to address the urgent needs of the COVID 19 pandemic. Both the financial commitment from the government to many sectors of Canadian society, coupled with the generosity and community-minded spirit of Canadian companies and citizens, has been staggering. After 100+ years and tens of thousands of deaths, it is time for the same commitment, urgency and compassion to be shown to people with ALS. Canadian patients want to work with all stakeholders to make ALS treatable and curable. Time is of the essence. ALS is not an incurable disease. It is an ignored and underfunded disease, especially in Canada.
| Background & Context for this Position Paper |
We are Canadians with ALS. We have written this paper to draw your immediate attention to an ongoing health crisis in Canada that only became more acute with the COVID-19 pandemic.
We are your doctors, firefighters, lawyers, teachers, business owners, executives, military members, managers, tradespeople and home-makers. We are your families, your neighbours and your friends. We are diagnosed with ALS and sent home to die. Year, after year, after year.
We, along with our families, friends and communities, no longer accept the status quo which has rendered us expendable for so many decades and which has seen us in Canada receive substandard care, compared to other health conditions, for far too long. Oncology, for example, has dedicated approval pathways enabling more efficient regulatory reviews, and utilizes collaborative frameworks (see discussion of Project Orbis below) that harmonize review processes with international partners.
ALS / SLA Action Canada
ALS / SLA Action Canada is a new patient-led initiative advocating for urgent access to promising therapies for Canadians living with ALS.
We, the patients, have unique and valuable insight into ALS: we live with it every day. Our voices and lived experience must significantly inform what the research priorities are, where funding should go, and what barriers need to be removed in the current therapy approval and clinical trial processes.
While we support, and are highly appreciative of, the programs and services offered by the ALS societies across Canada, these societies lack the resources to address the all of the priorities of all Canadians with ALS, their families and their communities.
We formed ALS Action Canada because we saw a gap in patient-led advocacy to pursue rapid access to promising new ALS therapies and clinical trials. We believe there is an ALS Crisis, and therefore crisis management strategies and tactics should be brought to bear.
Amyotrophic Lateral Sclerosis Overview
For 100+ years, thousands and thousands of people diagnosed with ALS were sent home by their doctors to die a horrific death because there were no meaningful treatments available. This represents an ongoing health crisis in Canada and around the world.
ALS (also known as Lou Gehrig’s disease) gradually paralyzes people because the brain is no longer able to communicate with the muscles of the body that we are typically able to move at will. Over time, as the muscles of the body break down, we lose the ability to walk, talk, eat, swallow and eventually breathe.
Eighty percent (80%) of people with ALS die within two to five years of being diagnosed. Those who live for longer than five years usually rely on a ventilator through a tracheotomy and can only communicate with their eyes and eye-gaze technology. It has been described as living in a “glass coffin”.
Approximately 3,000 people in Canada at any given time have ALS, and each year approximately 1,000 people in Canada die from ALS and a similar number are newly diagnosed with ALS.
As such, we knew on January 1, 2020, before the COVID 19 pandemic, that approximately 1,000 people in Canada would die this year from ALS because that is approximately how many died last year and the year before that.
According to the National Center for Biotechnology Information, the lifetime risk of developing ALS is 1 in 400, which is about equal to Multiple Sclerosis and is five times higher than Huntington’s disease. However, the rapid progression and deaths of people with ALS have prevented the establishment of a critical mass and a loud collective voice. Often, one of the first things taken from us is our ability to speak. This dynamic is driving our demands for urgent action.
Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. Many members of ALS Action Canada were diagnosed in their 20s.
There are no known lifestyle choices associated with ALS – we have not brought this on ourselves. In fact, there is a higher incidence of ALS in people who are first responders, high-level athletes and those who have served in the military.
There are two types of ALS: “sporadic” ALS which afflicts 90% to 95% of people with ALS and “genetic” or hereditary ALS which afflicts the balance.
At present, there are only two approved drugs in Canada to treat ALS: (1) riluzole (Rilutek), approved in November, 2000, which may extend life in the range of 6 to 19 months; and (2) edaravone (Radicava), approved nearly 18 years later in October, 2018, which may make a modest difference in the rate of progression for some people.
The Federal Government’s Motion 105
In August 2016, Member of Parliament Mauril Bélanger passed away eight months after being diagnosed with ALS. Shortly thereafter, a group of MPs and Senators formed an all-party ALS Caucus. Then, in April 2017 Motion 105 (M-105), sponsored by Judy Sgro, MP, was unanimously passed by the House of Commons. It provides:
“That, in light of the death of over 1000 Canadians each year, including the tragic loss of the Honourable Mauril Bélanger, former MP for Ottawa—Vanier on August 16, 2016, as a consequence of Amyotrophic Lateral Sclerosis (ALS), the House: (a) reiterate its desire and commitment to, in collaboration with provincial and territorial stakeholders, combat ALS via research and awareness; and (b) call upon the government to play a leadership role in supporting ALS research, and to support national efforts to find a cure for ALS at the earliest opportunity.”
While we are grateful that M-105 was passed, we believe that it has never had life – our lives – breathed into it. We are committed to see this now happen.
ALS Research and Treatment Options Benefit Other Brain Diseases
ALS has biological commonalities with other neurodegenerative diseases such as Parkinson’s, Multiple Sclerosis, Huntington’s Disease and Frontotemporal Dementia, although ALS typically has a faster progression to end of life, and is 100% fatal.
Advancing ALS research and treatment breakthroughs could benefit all Canadians living with Parkinson’s Disease (100,000 Canadians), MS (77,000), Huntington’s Disease (21,000) and Frontotemporal Dementia (15,000) – totaling in excess today of 200,000 Canadians who could benefit.
| The ALS Therapy Approval Process in Canada |
This is a time of unprecedented hope for ALS. For the first time ever there are numerous promising therapies in the clinical trial processes for sporadic ALS. There is also a phase 3 clinical trial therapy that appears to be stopping the progression of a certain type of genetic ALS.
However, Canada’s ALS therapy approval is slow, overly complex and potentially punitive to therapy developers, relative to jurisdictions elsewhere in the world. ALS therapy sponsors who want to bring their therapies to Canada face barriers. As a result Canadians with ALS do not have access to ALS therapies at the same time as Americans, Europeans and people in other countries.
That said, we are encouraged by two recent developments: first, Canada is a participant in an international agreement that allows for the fast tracking of oncology therapies, which is a model that would serve the discovery of new ALS therapies. Second, recent changes to the Canada Food and Drug Act provide a new pathway for accelerating the approvals of ALS therapies. These developments / programs are discussed in further detail below.
Promising New Therapies
There are approximately 80 ALS clinical trials in various stages worldwide and several late stage trials, listed below, are scheduled to complete in late 2020 or early 20211. However, only one of these trials (for sporadic ALS) is taking place in Canada.
| Therapy | Company / Sponsor | Trial Sites in Canada |
| NurOwn | Brainstorm Cell Therapeutics Inc. | No |
| RNS60 | Revalesio /Mario Negri Institute | No |
| Arimoclomol | Orphazyme | Yes |
| AMX0035 | Amylyx Pharmaceuticals Inc. | No |
NurOwn is the most anticipated of these phase 3 trials. It is being conducted in the US by Brainstorm Cell Therapeutics Inc. It is a stem cell therapy and the trial is scheduled to complete in November 2020. We are aware that there is a company in Montreal willing to provide a facility to allow for the NurOwn therapy to be administered in Canada, if it is proven to have efficacy.
Given Canada’s cumbersome regulatory system for approving and publicly reimbursing new therapies, we have no confidence that Brainstorm and the other sponsors of new therapies will immediately apply to bring them to Canada should they be approved by the FDA or the equivalent regulator in other countries.
1 Dr. Merit Cudkowicz, MD, Chief of Neurology Massachusetts General, Director of the Seam M. Healey Center for ALS, Professor, of Neurology, Harvard Medical School Webinar, Hosted by Everything ALS, June 3, 2020.
Canada’s Poor Record for Approving ALS Therapies
Canada has an ineffective, sluggish process for timely approval of ALS therapies after they are approved in the US. Riluzole was approved by the US Food & Drug Administration (“FDA”) in December 1995 but was not approved by Health Canada until November 2000.
Radicava (edaravone), the first ALS-related drug to receive FDA approval in over 20 years, was approved by the FDA in May 2017 but not approved by Health Canada until October 2018. Furthermore, as of August 2020, two provinces have still failed to approve edaravone for public funding.
Project Orbis – The Oncology Framework Example
Where we are hopeful for an intervention is on the application of a policy framework already in use for cancer treatments. Canada is a signatory to several international reciprocal agreements, treaties, and conventions that provide excellent precedent frameworks for rapid development and deployment of an ALS focused-agreement that would fast track access to ALS therapies in Canada.
Project Orbis – a collaborative initiated in September, 2019 involving Health Canada, the US FDA Oncology Center of Excellence (OCE), the Australian Therapeutic Goods Administration, Singapore’s Health Sciences Authority (HSA) and Swissmedic – provides a framework for concurrent submission and review of oncology products among these international partners. 2
The first therapy approved under Project Orbis occurred in April 2020, which allowed for the immediate use of the treatment in all signatory countries. Applying this type of framework to ALS therapies would eliminate the standard 180-day review period under Health Canada’s Priority Review, during which 500
Canadians, including several members of ALS/SLA Action Canada, will likely die. Canadians with ALS do not have the 180 days to wait for a review period.
Canada Food and Drug Act Changes: Mechanisms to Accelerate Access
We are encouraged that in May 2020 changes were made to the regulations under the Canada Food and Drug Act that could create a mechanism for accelerated access to ALS therapies by easing the pathway for companies offering ALS therapies and treatments.3
Currently, the federal-provincial-territorial reimbursement approach adds tremendous administrative and a time burden on ALS patients and caregivers, when quality time, days and weeks with loved ones, is the priority. We believe this burden can be mitigated if Health Canada utilizes the newly introduced pathway to create a centralized and simplified mechanism for all ALS patients in Canada to administer the public reimbursement process.
2https://www.canada.ca/en/health-canada/news/2019/12/international-collaboration-among-canadian-us-and-australian regulators-leads-to-new-options-for-the-treatment-of-cancer.html, https://www.fda.gov/about-fda/oncology-center excellence/project-orbis
3Specifically, a regulatory amendment was made by Health Canada, giving the Minister of Health the authority to add or delete a description of a therapeutic product, or a class of therapeutic products, to schedule G at their discretion.
Special Access Programme
The Special Access Programme (SAP) under the Canada Food and Drug Act4 which considers requests for access to unauthorized drugs on a case by case basis, is intended for serious or life-threatening conditions where conventional therapies have failed, are unsuitable, or are unavailable in Canada either as marketed products or through enrollment in clinical trials.. This is another mechanism that we believe is worth exploring in order to quickly get FDA approved therapies or phase 2 and 3 ALS therapies, such as those being employed in platform trial models, into the bodies of Canadians en masse.
We acknowledge that the federal government currently states that the SAP is not intended to be a mechanism to: (a) promote or encourage the early use of drugs, or (b) conduct research or to circumvent the clinical trial or drug review process. However, we would like to fully explore the possibilities of this program, or an amended program, to cover all ALS patients in one SAP application, as opposed to thousands of individual applications.
The Patented Medicine Prices Review Board: Proposed New Pricing Regulations
We are extremely concerned that the federal Patented Medicine Prices Review Board’s (PMPRB) proposed new pricing regulations will lower the likelihood of ALS treatments coming to Canada, rather than increase them. Based on the regulations initially proposed, for approximately 80% of new therapies, the price set arbitrarily by the PMPRB would be far below the drug sponsors’ cost of product research and development. As a result, many drug companies have indicated they will not bring new therapies to Canada on a priority basis5.
The PMPRB’s new pricing regulations were scheduled to come into effect on July 1, 2020. However, the PMPRB recently announced that the new pricing regulations will be delayed until January 1, 2021. On June 19, 2020 a revised set of draft guidelines were issued (referred to as the “June 2020 Guidelines”), followed by a consultation period.
We respect PMPRB’s consumer price protection mandate and legislative intent to reduce the cost of patented medicines, with one caveat: we are a small group of terminally ill Canadians with rapid progression. For us, ensuring the implementation of the proposed PMPRB guidelines don’t impede urgent access to promising therapies for ALS, is literally a matter of life and death. We therefore support the following recommendations:
1. That the Federal Government require PMPRB to engage an independent third party to conduct a formal assessment of the real-time and potential impacts of the reforms on access to therapies and research investment in Canada (including clinical trials), with specific consideration to therapies for rare diseases, before the PMPRB guidelines are implemented.
2. That the PMPRB undertake a phased approach to enacting proposed reforms as contemplated under the formal assessment as set out in 1. above. This ensures the impact of each change on research investment and access to therapies for both rare and
4 The SAP is supported by sections C.08.010 and C.08.011 of the Food and Drug Regulations.
5 Canadian Organization of Rare Disorders (CORD) webinar -Drug Launches: What Influences the Decision to Deploy New Medicines?, May 6, 2020
non-rare disease therapies can be fully assessed. Only then should additional reforms be considered. For people living with ALS, the impact of these changes has life and death consequences. We therefore further ask that the PMPRB compassionately provides any and all potential drugs and treatments for ALS with an exception status to PMPRB regulations.
3. That the PMPRB implements a distinct pathway for medicines for rare disease, recognizing, a) the devastating implications of our disease requires rapid approvals, b) the need for specialized expertise to provide input to the decision-making process, and c) the small patient population associated with such drugs imposes a relatively nominal impact on the overall health care spending in Canada.
4. That the Federal Government require that PMPRB decision-making and processes include patient representatives.
| Coverage by Provinces for Approved ALS Therapies |
Although Radicava (edaravone) was approved in October 2018 by Health Canada it took until April 15, 2020 for the pan-Canadian Pharmaceutical Alliance negotiation process6for this drug to conclude.
Following the pan-Canadian Pharmaceutical Alliance negotiation process the provincial governments must still each approve Radicava before it is covered through their respective provincial health care programs and available to all Canadians.
To date, eight provinces have approved edaravone (Radicava): Quebec (April), Ontario (May), Alberta (June), Saskatchewan (June), Manitoba (June), New Brunswick (June), Nova Scotia (July), Manitoba (July) and British Columbia (August). However, this public funding comes with restrictive eligibility, typically, 1) a diagnosis of probable or definite ALS, based on standardized criteria; 2) less than 2 years since symptom onset; 3) normal lung function; and 4) a score of at least 2 on each element of the ALS functional rating scale. As a result, not only did it take over eighteen months before the majority of provinces approved edaravone, but these approvals exclude a significant portion of Canadians living with ALS. For these patients the only options are to either not take the medication, or pay privately. While importing edaravone from Japan is cheaper than purchasing it in Canada, it still comes at great personal cost (~ $10,000 / year).
This approval process must be amended immediately.
| ALS Clinical Trials in Canada |
The Canada Health Actsets out the primary objective of Canadian health care policy, which is “to protect, promote and restore the physical and mental well-being of residents of Canada and to facilitate reasonable access to health services without financial or other barriers.” At present, access to ALS clinical trials is one of the very few “health services” available to someone newly diagnosed with ALS, and these are rare in Canada.
6 The pan-Canadian Pharmaceutical Alliance is an alliance of the provincial, territorial and federal governments that collaborates on a range of public drug plan initiatives to increase and manage access to clinically effective and affordable drug treatments.
ALS Clinical Trials Currently Available in Canada
While the number of ALS clinical trials is increasing worldwide, we need to be prepared to ensure these new trials have operational sites in Canada (See Appendix A). Further, not all provinces within Canada host clinical trials; British Columbia (see Appendix B) and Manitoba are the two most prominent examples of provinces that do not offer trials.
This means that Canadians with ALS must, in most cases, travel out-of-province or out-of-country to participate in clinical trials. Yet, as ALS progresses travel becomes much more arduous if not impossible. Further, the COVID-19 pandemic has significantly restricted travel to the US, as well as in Canada, as the Public Health Agency of Canada has recognized people living with ALS as a vulnerable population amidst this pandemic.
The Canadian Clinical Trial Network
The Canadian Clinical Trial Network project is spearheaded by the Montreal Neurological Hospital (“MNH”). The Clinical Research Unit at the MNH is the largest in Canada with ~15% of all Canadian clinical trials across all fields of medicine taking place there (over 100 trials in 2018-2019). Currently, there are no national networks supporting early-stage clinical trials for new therapies for ALS and other rare neurological diseases. The MNH is spearheading a project that would create a national network of clinical trial sites capable of conducting early-phase and proof-of-concept trials for ALS and other rare neurological diseases that will support and foster clinical trial excellence in neurology in Canada. Given their expertise and knowledge, the MNH will be the coordinating hub for the Canadian Clinical Trial Network with satellite locations overseen by the MNH across the country.
Among other efficiencies, this will allow for a centralized and singular “independent review board” (IRB) process instead of an IRB at each trial site (e.g., Montreal, Toronto, Edmonton) having to engage in essentially the same review. By way of example, the phase 3 Ultomiris clinical trial by Alexion has been reviewed and approved by the IRB at MNH and MNH is starting to screen and enroll patients. The IRB in Edmonton has not yet completed its review and so Edmonton is not yet screening and enrolling patients. The total estimated cost for the entire Network creation is $14.5 million of which over $8 million will be invested at the MNH with the rest invested at the hub sites across Canada. The MNH has already raised over $1 million and is looking for additional funding.
At present, we are unclear how the Clinical Trial Network fits with the Canadian ALS Research Network (“CALS”) which we understand may have a similar focus. It is our intent to lend our support to the network that is most expedient at bringing ALS clinical trials to Canada, and engages with clinicians interested in ALS research.
| ALS Research in Canada |
It appears that Motion-105 has not yet led to any direct government funding for ALS research and as a result ALS research in Canada is largely dependent on private donations. This has resulted in an incredibly bleak and piecemeal ALS research landscape in Canada.
ALS Canada Research Program
ALS research in Canada is primarily funded through the ALS Canada Research Program. The ALS Canada Research Program is supported by donors to the ALS Society of Canada and from provincial societies through a portion of the proceeds from the annual Walk to End ALS. Further support is provided by
ALS/SLA Action Canada www.alsaction.org @alsactionCanada 10 | Page
Brain Canada (through a matched funding arrangement), and past funding contributors include the Canadian Institutes of Health Research (CIHR), the ALS Association and the Muscular Dystrophy Association (MDA).
The current level of public and private funding of ALS research only enabled the ALS Society of Canada to allocate $1.4 million to research in its 2019 funding program; $1.4 million is grossly inadequate to fund a research program that affects tens of thousands of Canadians with neurodegenerative disease.
CAPTURE ALS
In each of the last several years the ALS Society of Canada has requested the federal government to provide $7 million in annual funding (for five years) to CAPTURE (Comprehensive Analysis Platform To Understand, Remedy, and Eliminate) ALS, but this request has been repeatedly ignored.
CAPTURE ALS would allow researchers around the world to study underlying disease pathology in order to develop personalized medicine and determine drug efficacy in different patients. This project would make Canada a key contributor to landmark medical discoveries and Canadians one of the first beneficiaries. CAPTURE ALS is a national initiative and will be delivered through four ALS clinics at institutions across Canada. Funding of CAPTURE ALS will also allow the government to act on the National Dementia Strategy, established in 2017.
The federal governmentshould consider this: not only does CAPTURE ALS lend to the data analysis so desperately required to ‘solve’ ALS; it can also make Canada a world leader in foundational ALS research with the secondary benefits of attracting pharmaceutical companies and scientists alike.
That said, before adding our support to this funding request we would like to understand it better and determine the potential for how it fits with the Precision Medicine Program already underway at the ALS Therapy Development Institute in the US.
Project MinE
The ALS Society of Canada is also leading Canada’s fundraising efforts for Project MinE to support the mapping and analysis of up to 1,000 DNA profiles.
Project MinE is a multi-national initiative with more than 15 participating countries. It will map the full DNA profiles of 15,000 people with ALS and 7,500 control subjects, establishing a global resource of human data that will enable scientists worldwide to understand the genetic signature that leads someone to develop ALS.
Before adding our support to this funding request we would like to understand it better. Research Undertaken at Canadian Universities and Hospitals
ALS research in Canada is undertaken at Canadian universities and hospitals. However, to our knowledge, there is no central registry that sets out what this research is, who funds it and what level of funding it receives.
| ALS Resources in Canada |
ALS Societies Across Canada
In each province, there is an independent ALS society that offers programs and services to people with ALS and their families. The societies have adopted a federation model to work together. The ALS Society of Canada merged with the ALS Society of Ontario, giving the organization a combined mission for advocacy and support for people living with ALS in Ontario and a national mandate (e.g. advocacy, research).
We are very grateful to the societies and for the services and programs they provide. Given the long predicament of no promising ALS treatments and insufficient funding, the societies have had no option but to focus on community-based support rather than research and treatment options.
By way of example, the ALS Society of BC offers a myriad of services to people with ALS at no cost – an equipment loan program of medical equipment (wheelchairs, walkers, scooters, bathroom aids, lifts, hospital beds, technology, etc.), mobile clinics, psychological treatment, support groups, caregiver programs, a kids camp, transportation assistance, professional development opportunities for the ALS Clinic’s allied healthcare professionals and some funding for genetic ALS testing.
In 2019, the Society’s total revenue was only $2.627 million. Of this, $1.115 million was spent on the Patient Service/Quality of Life programs noted above. Only $225,000 of the monies received by the Society in 2019 (less than 10%) was allocated to research.
ALS Clinics – Provincial Disparities in Care and Treatments
There is an ALS clinic in most provinces that provide a range of care and services. The clinics at the Montreal Neurological Hospital and Sunnybrook Health Sciences Centre in Toronto are examples of CALS clinics that offer leading ALS care (within the constraints of the Canadian system outlined in this paper).
At the other end of the continuum, as an example, the BC ALS Clinic at the GF Strong Rehabilitation Centre provides a care environment that falls well short of that in other large provinces (see Appendix B.). While the recent announcement of the planned creation of the BC ALS Centre of Excellence is encouraging, this Centre will not become operational unless / until the ALS Society of BC raises another $3 million, an enormous sum of money given the Society’s fundraising history.
These provincial / regional disparities in care and treatment options persist, and must be addressed.
| A Time of Unprecedented Hope in the Fight Against ALS |
As noted, this is a time of unprecedented hope for people with ALS due to: 1) over 160 drug companies now working on projects in the ALS space; 2) promising ALS therapies in the clinical trial pipeline; 3) a breakthrough therapy in the fight against genetic ALS; 4) innovative new clinical trials formats; and 5) an explosion of new patient-led advocacy initiatives.
New Therapies That May Be Promising
In addition to the phase 3 clinical trials scheduled to be complete in late 2020 or early 2021, noted above, there are several other phase 3 trials focused on sporadic ALS enrolling patients now or about to enroll patients.7
There are also three different “Treg” therapies being developed at present, all leveraging Dr. Stanley Appel’s foundational work through the Methodist Hospital System. Dr. Merit Cudkowicz, a leading expert on ALS8 and head of the Healey Platform ALS Trial (see discussion below) is of the view that there is clear promise for the Tregs therapy, in some form, as far as stopping progression of ALS. The different versions currently are:
1) Dr. Appel’s process that, in a small Phase I trial of three people, was shown to have stopped ALS progression in patients while they received treatments. This is currently in a small Phase 2 trial with eight participants. It will likely be necessary for it to then move to a Phase 3 trial which will require several million dollars. The cost of the therapy currently is ~$100k/year per patient, which is clearly prohibitive without committed funding.
2) RAPA-501, developed by RAPA Therapeutics, LLC, is an “off-the-shelf” version of Tregs and has received FDA approval to initiate a Phase 1 trial.
Finally, there are other therapies that are being developed by non-profit organizations in the US that are solely focused on ALS research. These include Prosetin by Project ALS and AT-1501 by the ALS Therapy Development Institute. Given that the T-Reg, Prosetin and At-1501 trials are being conducted by hospitals or non-profits they are at risk of not having sufficient funding to complete their trials in a timely manner much less bring them to Canada. Canadians deserve access to these trials in Canada. This requires a streamlined regulatory environment and funding availability sufficient to incent clinicians in Canada to conduct such trials.
A Breakthrough Therapy for Genetic ALS
Chris Snow, the Assistant General Manager for the Calgary Flames, publically announced in December 2019 that he had been diagnosed with ALS in June 2019. Chris has a type of genetic ALS that affects 2 percent of ALS patients and that had already killed his father, two uncles and his 28 year-old cousin. The average life expectancy for this type of ALS is 6 to 18 months.
Almost immediately after his diagnosis Chris enrolled in a Phase III clinical trial at Sunnybrook Health Sciences Centre in Toronto for those with his type of genetic ALS. Chris has since been able to participate in this same clinical trial out of Calgary.
The therapy, tofersen by Biogen, seems to be working in that Chris’ ALS progression has essentially stopped since he has been in the trial.
Chris and his wife, working with the Calgary Flames Foundation, are now raising money for ALS research under the #SnowyStrong campaign and their #Trickshot4Snowy video campaign has recently gone viral on Twitter.
7 Dr. Merit Cudkowicz, MD, Chief of Neurology Massachusetts General, Director of the Seam M. Healey Center for ALS, Professorof Neurology, Harvard Medical School Webinar, Hosted by Everything ALS, June 3, 2020. 8 See above footnote
Innovative Clinical Trials – the HEALEY ALS Platform Trial
For the first time, there is an innovative clinical trial – the HEALEY ALS Platform Trial – about to commence in the US. Borrowing from successes in cancer drug development, the Sean M. Healey & AMG Center for ALS at the Massachusetts General Hospital, in partnership with the Northeast ALS Consortium (NEALS) and TackleALS, are leading the first Platform Trial initiative for ALS. Dr. Merit Cudkowicz is spearheading the trial.
Traditionally, each trial evaluates one drug at a time, and requires lengthy start-up and execution times. Platform trials, conversely, test multiple drugs at the same time, using specialized statistical algorithms and tools. New regimens (drugs) can be added as they become available thereby decreasing or eliminating the gap in time from identification of a rationale therapy to testing. Thus, the focus is on the disease, rather than any individual experimental agent, and the platform remains open long-term until successful cures are found.
The Platform trial will be hosted at 54 sites across the US and, while originally scheduled to start in March 2020, it is now expectedto start in summer 2020 due to the COVID-19 pandemic.
The Platform trial organizers and therapy sponsors have expressed an interest in expanding this trial into Canada but there is no funding in place to allow this to occur. If the trial does not come to Canada, Canadians with ALS will have to travel to the US, if possible, and at their own expense, to participate in it.
Right to Try / Expanded Access / Special Access Programme
We have been advised that several drug companies participating in the HEALEY ALS Platform Trial are willing to make their therapies available to Canadians in Canada if their costs – estimated to be $5,000 to $10,000 per person per year for current therapies – are covered. Drug companies would increase the size of their data pools and Canadians would get access to vetted therapies at a manageable cost. Canadians would have access to promising experimental therapies with none being placed in a placebo control group. This option would provide the federal government a low-cost, ready alternative to accelerate treatment optionsfor its citizens while concurrently developing Canadian solutions.
Unprecedented Mobilization and Advocacy in the US
This is a time of unprecedented patient led mobilization and advocacy in the US concerning the need for ALS treatments. By way of example:
● In January 2019, I AM ALS.org was launched by lawyer and former President Obama staffer and federal prosecutor, Brian Wallach who was diagnosed with ALS in 2017. Brian was profiled in People magazine and on the Today Show and CNN, among other national media outlets, and now has 43,000 followers on Twitter. I AM ALS has received support from President Obama and the Obama Foundation and the Chan–Zuckerberg Initiative. It has placed ads in Times Square and has been an instrumental player in most major ALS announcements and legislative developments over the last 12 months.
● Former NFL football player, Eric Stevens, was diagnosed with ALS in 2019 at the age of 29, a month after his wedding. Together with his wife, Amanda, they have formed Team StevensNation and have appeared on The Ellen Show and have received vocal support from golf legend, Fred Couples, among others. Amanda’s Ted Talks about ALS is one of the most powerful statements about the urgent need for ALS treatments ever produced.
● The No More Excuses group has taken a page from the aggressive ACT-UP movement that led the advocacy to find treatments for AIDS in the 1980s. Their Facebook and Twitter sites, as well their YouTube Channel (ALS News Now), are strongly advocating for immediate access to NurOwn and other promising therapies. They held their second rally in Washington, D.C. last months and received coverage in Newsweek, among other media.
Unprecedented Political Leadership / Legislation in the US
The patient-led mobilization and advocacy in the US has led to unprecedented political action and legislative results. By way of example:
● In January 2020, former NFL football player, Steve Gleason, was awarded the Congressional Gold Medal for his work as an advocate for people with ALS. Steve was diagnosed with ALS in 2011 and now uses his eyes and assistive technology to function. The Congressional Gold Medal is the highest honour that Congress can bestow on a civilian. Gleason and his foundation were the driving force behind The Steve Gleason Act, which was signed into law by President Obama in 2015 to make critical technology available to patients through Medicare and Medicaid.
● A bi-partisan House of Representatives ALS Caucus was formed in June 2019 and now has over 130 members. A bi-partisan Senate ALS Caucus was formed in January 2020 and has 18 members. As a result, almost 30% of the members of Congress are part of an ALS caucus.
● In May 2020, a bipartisan bill (Accelerating Access to Critical Therapies for ALS Act) was introduced in the House of Representatives that will create an infrastructure to fund early access to promising therapies discovered through clinical trials for patients suffering from fast progressing neurodegenerative and terminal diseases like ALS. Specifically, it will make $75 million available in FY 2021 and 2022 for a pilot program to support expanded access programs. It will bring treatments for rapidly progressing neurodegenerative diseases to patients beyond the ongoing clinical trial and establish a Center of Excellence for Neurodegenerative Diseases at the FDA to accelerate the development and approval of therapies for neurodegenerative diseases.
● Also in May 2020 a bill (Promising Pathway Act) was introduced in the Senate that will speed up the regulatory processes for getting drugs showing benefits to the patients who need them. The bill requires the FDA to establish a rolling, real-time, priority review pathway to evaluate provisional approval applications for drugs intended to treat, prevent, or diagnose serious or life-threatening diseases or conditions, including those that pose a threat of epidemic or pandemic. Under this pathway, provisional approval would be granted by the FDA to drugs demonstrating substantial evidence of safety and relevant early evidence of positive therapeutic outcome(s).
● In June 2020, the US National Institute of Health announced that it plans to invest $25 million over five years in a new program to spur innovative research on ALS. ALS will be part of the NIH Common Fund’s High Risk, High Reward program
| The Plan to End the ALS Crisis |
We are fighting for the right to live. ALS does not have to be an incurable disease. It is an underfunded and ignored disease, especially in Canada.
We have seen how quickly and capably Canadian governments can mobilize to address the COVID-19 pandemic and the financial commitment they have made to many, many sectors of Canadian society. We have also seen how generous and community-minded Canadian companies are.
After 100+ years and tens of thousands of deaths, we think it’s time for this same commitment, urgency and compassion to be shown to people with ALS.
We are respectfully requesting that the following action to be takento save our lives, the lives of the next 1000 Canadians who will be diagnosed this year, and end the ALS Crisis:
Federal Government
Ensure Immediate Access to Promising Therapies that Are Approved in Other Countries
1. Develop and implement a framework, similar to Project Orbis, to concurrently / immediately approve these therapies for use in Canada once they have been approved by the FDA or the equivalent regulator in other Five Eyes countries (US, Australia, New Zealand and the United Kingdom) or even G-20 countries. While there is currently a Priority Review process in place it is based on a 180-day timeline during which 500 Canadians will die of ALS.
2. Provide Canadians with access to therapies that will be made available through the HEALEY Platform ALS Trial leveraging the US Right to Try / Extended Access mechanisms and the Canadian Special Access Program. Also assess the use of the same Right to Try / Extended Access / Special Access Program for other therapies in phase 3 clinical trials such as NurOwn and AMX0035.
3. Ensure that the Patent Medicines Price Review Board’s regulations encourage the availability of ALS clinical trials and therapies in Canada, and/or exempt ALS therapies from the new pricing rules. Low pricing proposed in the new regulations will detersponsors, most of whom are in the US, from bringing their ALS clinical trials and new therapies to Canada.
4. Ensure that other regulations (e.g. packaging, marketing) do not de-incentivize these sponsors from bringing their therapies to Canada.
5. Work with the ALS community and industry to find other ways to incentivize these sponsors to immediately bring their therapies to Canada.
Play Leadership Role in Relation to Coverage Under Provincial Health Care Programs
6. Take all steps to ensure that all ALS therapies are immediately covered under provincial health care programs once approved by Health Canada.
The pan-Canadian Pharmaceutical Alliance9
Ensure Immediate Coverage for new ALS Therapies
7. Accelerate the pan-Canadian Pharmaceutical Alliance negotiation process so that it is no more than 60 days for ALS therapies.
Provincial Governments
Quickly Approve ALS Therapies for Coverage
8. Approve new ALS therapies for coverage under their respective provincial health care plans within 30 days of the pan-Canadian Pharmaceutical Alliance negotiation process concluding.
Provide Direct Funding to ALS Societies for Patient Service/Quality of Life Programs
9. Provide consistent and sufficient funding to their respective ALS societiesto operate their patient service/quality of life programs, so that all money raised by the societies through community fundraising can be directed to research, therapy development and clinical trials.
ALS Society of Canada
Modify Canada ALS Research Program funding criteria
10. Revise the Canada ALS Research Program funding criteria to include initiatives that are centrally important to people living with ALS today, such as treatment development and clinical trials.
Public / Private Partnerships
Bring More and Better Clinical Trials to Canada
11. Provide funding and any other necessary support to the Montreal Neurological Hospital (“MNH”) and other sites to bring the innovative Healey ALS Platform trial to multiple sites in Canada in 2020.
12. Provide funding and any other necessary support to non-profits in the US that have or will be initiating clinical trials for promising therapies, such that these trials can be brought to Canada in 2020 and 2021.
13. Provide funding and any other necessary to the Canadian Clinical Trial Network project being spearheaded by the MNH.
More ALS Research Funding
14. [Note: We are considering the most effective research funding target(s)]
9 The pan-Canadian Pharmaceutical Alliance is an alliance of the provincial, territorial and federal governments that collaborates on a range of public drug plan initiatives to increase and manage access to clinically effective and a ffordable drug treatments.
British Columbia Government
Establish the BC ALS Centre of Excellence and Offer Clinical Trials
15. Immediate and sufficient ongoing funding to transform the ALS Clinic at GF Strong into an ALS Centre of Excellence at the UBC Centre for Brain Health that is led by a full-time director and that conducts clinical trials, such that people in BC with ALS no longer have to travel out of province / out of country to receive treatment and thus hope. The recent announcement of the creation of the Centre is encouraging, but this Centre will not become operational unless / until the ALS Society of BC raises another $3 million, an enormous sum of money given the Society’s fundraising history.
| It’s Time for Canada to Collectively Fight to End the ALS Crisis |
We are fighting for the right to live. It is a human right, our human right as Canadians.
We, the patients, have unique and valuable insight into ALS: we live with it every day. Our voices and lived experience must significantly inform what the research priorities are, where funding should go, and what barriers need to be removed in the current therapy approval and clinical trial processes.
ALS should not be an incurable disease; it is an underfunded and ignored disease, especially in Canada.
We have seen how quickly and capably Canadian governments can mobilize together to address the COVID-19 pandemic and also provide the financial commitments to many sectors of Canadian society. We have also seen how generous, innovative and community-minded Canadian companies are.
After 100+ years and tens of thousands of Canadians who have died, we think It`s time. Time for this same level of commitment, urgency and compassion to be shown to Canadians who have ALS.
We would like to partner with you in supporting our efforts to enable the Plan in this document.
Thank you for your consideration of our requests. We look forward to receiving your input on this Plan and how we might work with you to move forward.
| APPENDIX A: Promising ALS Therapies |
Late stage trials scheduled to conclude in 2020 or early 202110:
| Therapy | Company / Sponsor | Trial Sites in Canada |
| NurOwn | Brainstorm Cell Therapeutics Inc. | No |
| RNS60 | Revalesio /Mario Negri Institute | No |
| Arimoclomol | Orphazyme | Yes |
| AMX0035 | Amylyx Pharmaceuticals Inc. | No |
| Tofersen (BIIB067)11 | Biogen | Yes |
Phase III trials enrolling patients now or about to enroll patients:
| Therapy | Company / Sponsor | Trial Sites in Canada |
| Masitinib | AB Science SA | TBD |
| Ibudilast | MediciNova | Yes |
| Ultomiris | Alexion | Yes |
| Reldesemtiv | Cytokinetics | No |
| Triumeq | TRICALS | No |
| Neuronata-R | Corestem | No |
There is also the Phase II T-Regs trial. This treatment stopped ALS progression in the three Phase I participants:
| Therapy | Sponsor | Trial Sites in Canada |
| T-Regs | The Methodist Hospital System | No |
Therapies being developed by non-profit organizations in the US that are solely focused on ALS research:
| Therapy | Sponsor | Trial Sites in Canada |
| Prosetin | Project ALS | No |
| AT-1501 | ALS Therapy Development Institute | No |
A comprehensive listing of ALS related clinical trials, the ALS Signal: Clinical Research Dashboard, can be found on the I AM ALS website at https://iamals.org/alssignal/ .
10 Dr. Merit Cudkowicz, MD, Chief of Neurology Massachusetts General, Director of the Sea n M. Healey Center for ALS, Professor of Neurology, Harvard Medical School, Webinar, Hosted by Everything ALS, June 3, 2020. 11 This therapy targets a form of genetic ALS.
| APPENDIX B: Regional Disparities in Care – The British Columbia Example |
The ALS Clinic at GF Strong (the “BC ALS Clinic”) serves all British Columbians who have ALS. Based on our collective experience of those in British Columbia we know that the BC ALS Clinic provides substandard care to people with ALS, as compared to ALS clinics in other provinces and in the United States. In saying this, we point to the following, by way of example:
1. Physician Staffing: Unlike ALS clinics in other large provinces, the BC ALS Clinic does not have a dedicated full-time neurologist to oversee the clinic and to provide leadership to drive it forward. Rather, it is staffed with four neurologists who all see ALS patients on a part-time basis. While we appreciate their involvement, part-time care should not be the standard and is not the standard in other provinces.
2. Multi-Disciplinary Services. The BC ALS Clinic offers certain multi-disciplinary services such as an occupational therapist, a social worker, a speech pathologist and a dietician. Communication support and equipment is provided by CAYA in partnership with the ALS Society of BC, and respiratory care is provided through the Provincial Respiratory Outreach Program (PROP) However, many ALS patients have experienced a lack of consistency and coordination amongst the Clinic, the regional health authorities and other service providers, in the delivery of certain of these services.
3. Wait Times: The majority of people in BC who are told that they have ALS are sent to the BC ALS Clinic for confirmation of their diagnosis and to be provided with information about what comes next. The prelude to this appointment is incredibly difficult. The wait time for an appointment to get into the BC ALS Clinic can be significant (e.g. two to three months). People with ALS in BC can get into ALS clinics in other provinces far faster than they can get into the BC ALS Clinic.
4. Location: The BC ALS Clinic is located in a dreary set of rooms in the basement of GF Strong. For many people, this location heightens the emotional trauma of being diagnosed with ALS and they experience more trauma with each follow-up appointment. In contrast, BC’s Multiple Sclerosis Clinic, Alzheimer’s Clinic, and Huntington’s Disease Clinic are located in a beautiful new and modern building at UBC, the Djavad Mowafaghian Centre for Brain Health.
5. Clinical Trials: Unlike the ALS clinics in many other provinces, including Alberta, Ontario and Quebec, the BC ALS Clinic does not host clinical trials for experimental therapies. British Columbians with ALS must travel out of province or out of country to participate in these trials and, as you can imagine, travel becomes more and more difficult for people with ALS as the disease progresses.
Moreover, because the BC ALS Clinic does not offer clinical trials, it does not offer hope and is, in essence, a palliative care clinic. The difference in culture / feel between the other ALS clinics that we have attended in Canada and the US (“we will overturn any stone to see if we can help you live”) and the BC ALS Clinic (“we are here to support you as you progress and die”) has been striking to us.
6. Specialized Testing: Approximately 5% to 10% of people with ALS have “genetic” or hereditary ALS (as opposed to sporadic ALS). Encouragingly, there are now some therapies in the clinical trial process that appear to be essentially stopping progression of certain types of ALS. However, the BC ALS Clinic does not test for genetic ALS as a matter of course and when it does test, it can take two to three months to obtain the results because the blood samples are sent to Alberta and testing is delayed until there are enough samples to make a “batch”.
The ALS Society of BC has started a fundraising campaign to raise $5 million to transform the BC ALS Clinic into the BC ALS Centre of Excellence. In partnership with the UBC Faculty of Medicine, this would see the clinic being moved to the UBC Centre for Brain Health, staffed with a full-time clinician-scientist and properly resourced to offer clinical trials.
To date, the Society has raised slightly over $1 million and the Province has provided a one-time $1 million matching grant. While we are grateful for government funding, this one-time grant of $1 million still requires the Society to fund-raise another $3 million before it even begins to start the recruiting process for a clinic director. This $3 million is an untenable amount given the Society’s historical ability to raise money, the impact that the COVID-19 pandemic has had on the Society’s fundraising and the patient service / quality of life programs that the Society needs to continue to fund. We are significantly concerned that it will take a number of years before the Centre is operational and offering clinic trials.