28 June 2025
Suzanne McGurn
President and CEO Director
Canada’s Drug Agency
E‑mail:Suzanne.McGurn@cda-amc.ca
Re: Health Technology Review, Cerliponase Alfa for Pediatric Patients With Neuronal Ceroid Lipofuscinosis Type 2 Disease
Dear Ms. McGurn,
The Canadian Organization for Rare Disorders is writing to express our concerns with the Health Technology Review: Cerliponase Alfa for Pediatric Patients With Neuronal Ceroid Lipofuscinosis Type 2 Disease published in Canadian Journal of Health Technologies, June 2025, Volume 5, Issue 6. The report was prepared by Canada’s Drug Agency in response to a request by British Columbia Ministry of Health to provide an “updated evidence review to support reimbursement decisions for cerliponase alfa, with a focus on evaluating their current discontinuation criteria” in application to the decision to terminate treatment for a specific patient, 9-year-old Charleigh Pollock.
According to Health Minister Josie Osborne, “Given the extraordinary circumstances, the ministry wanted to make sure no stone was left unturned in determining whether continuing treatment would benefit Charleigh.” As reported by Capital Daily (June 18, 2025), the Ministry interpreted the “CDA’s comprehensive review of the latest evidence in Canada and around the globe” as finding “no evidence to support the ministry continuing to provide coverage for Brineura, given the advanced stage of Charleigh’s condition.”
CORD has no insight as to whom the Ministry consulted to arrive at their extrapolation but, clearly, the CDA report was not a comprehensive review, but a rapid review conducted by one researcher. Notwithstanding the interviews with healthcare professionals and patient families to document real-world experience and evidence, the report’s conclusions are based on three primary studies (two observational with historical controls, one single-arm extension study) and two evidence-based clinical practice guidelines.
In 2019, CADTH proposed “trial-based stopping rules” for public reimbursement discontinuation, acknowledging that these were pragmatic rather than validated. Post-approval monitoring was recommended to collect real-world data to confirm and validate these clinical-trial measures. However, there was no systematic plan to collect and analyze real-world data, including patient outcomes.
In their 2025 review of updated real-world evidence, CDA confirmed:
- There is insufficient evidence to determine whether Brineura remains effective for patients with severe functional loss.
- There are no comparative studies that have tested the effect of continued vs. discontinued therapy after reaching a low motor-language score.
- The reported real-world outcomes (e.g., seizure control, alertness, quality of life) were not captured by the original motor-language scoring.
The CDA was given, and accepted, a very narrow question to apply to an updated evidence review: was there sufficient evidence to recommend a change in the 2019 discontinuation criteria? They were not asked more important “real-world” questions. Was there real-world evidence (healthcare professional and family) to indicate that Charleigh was or was not benefitting from treatment, based on other patient-relevant outcomes such as seizure control and social engagement, despite decline in the motor-language scores? How were other jurisdictions addressing patients relative to discontinuation criteria, patient outcomes, and potential impact of stopping treatment?
Under the expanded remit of CDA for appropriate use, we feel it is important for CDA to consider impact in addition to technology assessment. We would like to emphasize that international practice and evolving expert consensus support a more nuanced, individualized approach to therapy continuation decisions, particularly in ultra-rare conditions where statistical power is inherently limited. Decisions made solely on narrow trial-based criteria may not align with the values of patient-centered care and real-world impact.
We feel a truly comprehensive review is necessary in cases of discontinuation where the criteria are not based on validated measures and thresholds. Indeed, this very small patient population with limited patient history and experience with therapy demands this a different approach that is based on consensus rather than narrow body of evidence from clinical trial type designs that are neither feasible nor timely.
CORD is reaching out to the BC Health Ministry with a request for reconsideration and a process for conducting a prospective cohort study over a reasonable period to generate the evidence to determine the impact of Brineura on patients, including those with declining motor-language scores.
Thank you in advance for your support in this urgent matter. I look forward to your response. We all want what is truly best for the child.
Sincerely,
Durhane Wong-Rieger, PhD
President & CEO
Canadian Organization for Rare Disorders
durhane@raredisorders.ca
cc: The Honourable Josie Osborne, BC Minister of Health
cc: Jori Fales
CORD CDA Cerliponase_Alfa_Appeal letter.pdf
28 June 2025
The Honourable Josie Osborne
Ministry of Health
British Colombia
PO Box 9050, Stn Prov Govt
Victoria BC V8W 9E2
Phone: 250‑953‑3547
E‑mail: HLTH.Minister@gov.bc.ca
Re: Reconsideration of Discontinuance of Brineura for CLN2 patient
Dear Minister Osborne,
The Canadian Organization for Rare Disorders is the national alliance of rare disease patient organizations and individuals across Canada. We are writing to request a reconsideration of British Colombia’s decision to discontinue reimbursement of Brineura (cerliponase alfa) for BC patient 9-year-old Charleigh Pollack.
We appreciate that you have personally intervened a couple of times to extend access after the original drug termination decision was announced in February 2025, pending additional review. This included request to Canada’s Drug Agency to conduct a comprehensive review of new evidence to determine whether to change the discontinuation criteria, set at the same time as the access criteria in 2019 based on the clinical trial protocols. The specific question the CDA was asked to address was whether there was evidence that the discontinuation criteria should be changed. This, of course, was not the appropriate question to ask to determine whether Charleigh should remain on therapy.
There was very little likelihood of finding robust real-world that would validate, or not, performance on motor-language scores as thresholds for discontinuance. This is a very small patient population lacking natural history data. It was not surprising to find there were no prospective longitudinal post-market studies and similarly a lack of research to validate linkage between the clinical trial measures of motor-language scores and patient relevant outcomes.
The CDA report released in June 2025 found only three primary studies (two observational with historical controls, one single-arm extension study) and two evidence-based clinical practice guidelines that met the high standards for methodological rigor and relevance.
The CDA collected feedback from treating physicians and families, who reported benefits of improved seizure control, alertness, and quality of life, patient-relevant outcomes that were not measured in the original clinical trials. These outcomes did not factor into the analysis and conclusion of the sole research who had been commissioned to conduct, not a comprehensive review, but a rapid review. Seemingly, no other researchers or stakeholders were involved in the search, the analysis, and the writing of the conclusion. The conclusion of insufficient evidence to change the discontinuation criteria was inevitable. However, an equally valid conclusion, if a different question were asked, is that there is insufficient evidence to justify exercising the discontinuation criteria and taking Charleigh off therapy. Based on the information gathered, there is also insufficient evidence to conclude that Charleigh would not continue to benefit in terms of other outcome measures by staying on therapy. It is also true that there is insufficient evidence to conclude that Charleigh, or any other child with similar motor-language scores, would not suffer serious adverse effects, including resumption of seizures and withdrawal, if Brineura were discontinued.
In 2019, CADTH proposed “trial-based stopping rules” for public reimbursement discontinuation, acknowledging that these were pragmatic rather than validated. Post-approval monitoring was recommended to collect real-world data to confirm and validate these clinical-trial measures. However, there was no systematic plan to collect and analyze real-world data, including patient outcomes.
In their 2025 review of updated real-world evidence, CDA confirmed:
- There is insufficient evidence to determine whether Brineura remains effective for patients with severe functional loss.
- There are no comparative studies that have tested the effect of continued vs. discontinued therapy after reaching a low motor-language score.
- The reported real-world outcomes (e.g., seizure control, alertness, quality of life) were not captured by the original motor-language scoring.
The Canadian Organization for Rare Disorders posits that taking Charleigh off therapy at this time, based on the CDA Review, is unjustified, unconscionable, and a violation of her human rights.
We respectfully request your leadership to direct an appropriate review body, including healthcare professionals and patient representatives, to convene a case-level reconsideration and provide temporary continuation of therapy while this is conducted.
Thank you in advance for your support in this urgent matter. I look forward to your response. We all want what is truly best for the child.
Sincerely,
Durhane Wong-Rieger, PhD
President & CEO
Canadian Organization for Rare Disorders
durhane@raredisorders.ca
cc: Jori Fales