Reimbursement Recommendation

Donanemab (Kisunla)

Indication: For the treatment of adults with a clinical diagnosis of mild cognitive impairment or mild dementia due to Alzheimer’s disease, who are apolipoprotein E epsilon 4 (APOE4) heterozygotes or noncarriers, and who have confirmed amyloid pathology.

Sponsor: Eli Lilly Canada Inc.

Final Recommendation: Reimburse with conditions

What Is the Reimbursement Recommendation for Kisunla?

Canada’s Drug Agency (CDA-AMC) recommends that Kisunla be reimbursed by public drug plans for the treatment of adult patients in the early stages of Alzheimer disease (AD) (i.e., mild cognitive impairment [MCI] or mild dementia) who have evidence of amyloid in the brain and who are APOE epsilon 4 (APOE4) noncarriers or heterozygotes, if certain conditions are met.

Why Did CDA-AMC Recommend Reimbursement?

The Canadian Drug Expert Committee (CDEC) determined that Kisunla demonstrates acceptable clinical value versus placebo in adult patients with a clinical diagnosis of MCI or mild dementia due to AD, who are APOE4 heterozygotes or noncarriers, and who have confirmed amyloid pathology. This determination was enough for CDEC to recommend that Kisunla be reimbursed. Given that Kisunla is expected to be an additive treatment to best supportive care (BSC), acceptable clinical value refers to added value versus BSC alone.

Evidence from a clinical trial showed that, compared with placebo, treatment with Kisunla for up to 76 weeks provided a clinical benefit in slowing cognitive and functional decline in adults with MCI or mild dementia due to AD who were APOE4 heterozygotes or noncarriers and had confirmation of amyloid in the brain. CDEC determined that the evidence showed that Kisunla addresses a significant unmet clinical need in this patient population.

Which Patients Are Eligible for Coverage?

Kisunla should only be covered to treat adult patients aged 50 years or older who have a clinical diagnosis of MCI or mild dementia due to AD with confirmed amyloid pathology using a validated method, and who are APOE4 noncarriers or heterozygotes.

What Are the Conditions for Reimbursement?

Kisunla should only be reimbursed if prescribed by clinicians with expertise and experience in the diagnosis, management, and treatment of AD, in a setting with timely access to MRI. Infusions should be administered by qualified health care professionals trained to monitor for, recognize, and manage infusion-related reactions. Reimbursement should be continued after every 6 months of treatment, up to a maximum of 18 months, if there is evidence of ongoing benefit and patient safety can be ensured. Treatment should be discontinued if the patient’s condition progresses to moderate dementia, if they do not undergo the required MRI surveillance, or if they develop symptomatic amyloid-related imaging abnormalities (ARIAs) or moderate to severe radiographic ARIAs. Kisunla should not be used in combination with other monoclonal antibody therapies for AD and should only be reimbursed if its price is reduced.

Important budget impact considerations and organizational implications must be addressed for health systems to be able to adopt Kisunla.

Review Background

• Disease background: AD is a progressive and irreversible neurodegenerative disorder and the most common cause of dementia. It is characterized by worsening cognitive decline, functional impairment, and loss of independence that ultimately lead to complete dependence and substantial effects on patients’ health-related quality of life (HRQoL) and caregiver burden. As of 2025, an estimated 771,939 people in Canada were living with dementia, with AD accounting for approximately 60% to 80% of cases.

• Indication and reimbursement request: Donanemab (Kisunla) has been approved by Health Canada “for the treatment of adults with a clinical diagnosis of mild cognitive impairment or mild dementia due to Alzheimer’s disease, who are apolipoprotein E [epsilon 4] (ApoE [epsilon 4]) heterozygotes or non-carriers, and who have confirmed amyloid pathology.” The sponsor is seeking reimbursement for this patient population.

• Drug under review: Donanemab is an IgG1 monoclonal antibody directed against insoluble N-truncated pyroglutamate amyloid beta. It is available as a 17.5 mg/mL solution administered by IV infusion after dilution. According to the product monograph recommendations, donanemab is to be administered every 4 weeks as follows: 350 mg for infusion 1 (week 0), 700 mg for infusion 2 (week 4), 1,050 mg for infusion 3 (week 8), and 1,400 mg for infusion 4 (week 12) and beyond, to a maximum of 18 months.

• Treatment costs: At the submitted price of $1,027.17 per 20 mL vial, the annual cost of Kisunla is expected to be $51,359 per patient in the first year of treatment and $24,652 in the second year of treatment, based on the Health Canada–recommended dosage.

Highlights of Input From Interested Parties

The patient groups (the Alzheimer Society of Canada, the Alzheimer Society of Ontario, the International Federation on Ageing, and Dementia Network Calgary) noted the following regarding impacts of the disease, unmet needs, and important outcomes:

• MCI and AD affect memory, cognition, independence, emotional well-being, social participation, and identity, with progressive loss of autonomy and increasing dependence as the disease advances and substantial effects on family and caregivers.

• Existing treatments offer only modest, temporary, or uncertain benefits, with notable side effects and no meaningful impact on disease progression.

• The most important goals to patients and caregivers in the treatment of early AD are to halt or slow disease progression, preserve cognition and functional capacity, prevent memory loss, maintain quality of life, and reduce caregiver burden and the impact on caregivers’ own quality of life. Patients and caregivers emphasized the importance of extending the amount of time lived well.

The clinician groups (the Cognitive Neurosciences Clinic [at the University of Calgary], the Covenant Community Health Centre Lakewood, the Douglas Mental Health University Institute Memory Clinic [in Montréal, Quebec], Trillium Health Partners, the University of British Columbia Hospital Clinic for Alzheimers and Related Disorders, the Canadian Consortium on Neurodegeneration in Aging [CCNA], and the Consortium of Canadian Centres for Clinical Cognitive Research) and the clinical experts consulted by CDA-AMC noted the following regarding unmet needs arising from the disease and place in therapy for the drug under review:

• There is a need for publicly reimbursed and accessible disease-modifying therapies for patients with MCI and mild dementia due to AD that maintain or slow the decline in cognition, function, and independence.

• Donanemab is a disease-modifying therapy that is anticipated to be used as a first-line treatment for MCI or mild dementia due to AD and which may be used in combination with symptomatic treatments for mild dementia.

The participating public drug programs provided input regarding considerations for initiation and prescribing of therapy; health system implementation considerations; relevant comparators; and system and economic considerations.

Person With Lived Experience

A person with lived experience from New Brunswick shared his journey as a caregiver to both his parents, who were diagnosed with dementia and have since passed away. In 2005, his mother was diagnosed with dementia following brain biopsy, medical imaging, and clinical testing. His father had an unconfirmed diagnosis of MCI in the final 4 years of life; his father’s care team was uncertain if the cognitive decline was a sign of dementia or if it was related to the stress of his prior treatment with chemotherapy for stage IV colon cancer. Neither of his parents had been presented with drug options to manage their cognitive declines. He expressed his discouragement with the available support and resultant outcomes.

Patient navigation was almost nonexistent. He noted that the most challenging aspect for his parents and for himself as a caregiver was isolation. He recalled an interview with another caregiver that had occurred as part of a research study; the caregiver commented that she had wished her husband had been diagnosed with cancer instead of dementia because of the isolation and lack of available support for patients and families dealing with dementia. Living in New Brunswick meant they had to travel to Halifax, Nova Scotia, for specialized care. He expressed frustration that because of the state of the province, residents of New Brunswick do not have access to specialized clinics that could become trial sites for early access to dementia treatment. He noted that as a long-term caregiver, self-care was just not possible, which has affected his current physical and emotional well-being. He believes that having access to an effective early-onset medication for his parents would have given him time as the caregiver to develop a care plan for his parents and a regimen to look after himself.

Note: The perspectives shared by people with lived experience who present to the committee reflect their individual experiences and are not necessarily representative of all people with the same condition or course of treatment. Their insights provide valuable context about what a patient, support person, or caregiver might go through with this condition or treatment, helping to inform the committee’s deliberations. These narratives complement other forms of evidence and input and should be considered as 1 element contributing to a broader understanding of the condition and treatment under review.

Recommendation

With a vote of 11 in favour to 3 against, CDEC recommends that donanemab be reimbursed for the treatment of adults with a clinical diagnosis of MCI or mild dementia due to AD, who are APOE epsilon 4 (APOE4) noncarriers or heterozygotes, and who have confirmed amyloid pathology, only if the conditions listed in Table 1 are met.

Table 1: Reimbursement Conditions and Reasons

AD = Alzheimer disease; APOE4 = apolipoprotein E epsilon 4; ARIA = amyloid-related imaging abnormality; BSC = best supportive care; CDA‑AMC = Canada’s Drug Agency; CDEC = Canadian Drug Expert Committee; CL = Centiloid; CSF = cerebrospinal fluid; ICER = incremental cost-effectiveness ratio; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; MoCA = Montreal Cognitive Assessment; QALY = quality-adjusted life-year.

^aFor the statement regarding the size of the price reduction required, band 1 = 1% to 24%, band 2 = 25% to 49%, band 3 = 50% to 74%, and band 4 = 75% or greater.

Rationale for the Recommendation

Clinical Value

Based on the totality of the reviewed clinical evidence, CDEC concluded that donanemab demonstrates acceptable clinical value compared with placebo in adult patients with a clinical diagnosis of MCI or mild dementia due to AD, who are APOE4 heterozygotes or noncarriers, and who have confirmed amyloid pathology. Given that donanemab is expected to be an additive treatment to BSC, acceptable clinical value refers to added value versus BSC alone.

CDEC reviewed evidence from the TRAILBLAZER-ALZ 2 phase III trial (N = 1,736), a randomized, double-blind, controlled study in patients with early symptomatic AD and confirmed amyloid pathology. The committee focused on post hoc analyses of APOE4 heterozygotes and noncarriers (N = 1,447), consistent with the Health Canada–approved indication and the sponsor’s reimbursement request. Based on this evidence, CDEC determined that, compared with placebo, treatment with donanemab for up to 76 weeks provided a clinical benefit by slowing cognitive and functional decline in adults with MCI or mild dementia due to AD who were APOE4 heterozygotes or noncarriers and had confirmed amyloid pathology. Specifically, the between-group difference in the change from baseline in Integrated Alzheimer’s Disease Rating Scale (iADRS) scores at week 76, the primary end point, favoured donanemab and was considered clinically meaningful by the clinical experts consulted by CDA-AMC. Similarly, the between-group difference in the change from baseline in Clinical Dementia Rating Scale – Sum of Boxes (CDR-SB) scores at week 76, a secondary end point of key relevance to the review, favoured donanemab and was considered clinically meaningful. Results for other measures of cognition and function — including the Alzheimer’s Disease Assessment Scale – 13-item Cognitive Subscale (ADAS-Cog13), the Alzheimer’s Disease Cooperative Study – Instrumental Activities of Daily Living (ADCS-iADL) scale, and the Mini-Mental State Examination (MMSE) — were aligned with the findings for the iADRS and CDR-SB in favouring donanemab and supported a consistent pattern of benefit in slowing cognitive and functional decline. Furthermore, CDR-SB results from the TRAILBLAZER-ALZ 2 long-term extension (LTE) study suggest that the treatment effect of donanemab in slowing cognitive and functional decline in the indicated population may be maintained through 36 months relative to modelled natural disease progression. However, considerable uncertainty remains with the findings from the LTE study.

CDEC noted that donanemab was associated with a higher incidence of serious adverse events (SAEs) and ARIAs compared with placebo in the TRAILBLAZER-ALZ 2 trial. Notably, ARIA with edema or effusions (ARIA-E) events and ARIA with hemorrhage or hemosiderin deposition (ARIA-H) events occurred more frequently in the donanemab group than in the placebo group, with ARIA-E reported in 20.6% versus 1.8% of patients and ARIA-H reported in 27.6% versus 12.2% of patients, respectively. However, the committee recognized that early AD is a progressive and debilitating condition with limited treatment options. The committee also emphasized the importance of informed patient choice, with treatment decisions made in consultation with health care providers after considering the potential benefits and risks of therapy.

CDEC discussed that sources of uncertainty in the submitted evidence included the absence of established between-group minimal important differences (MIDs) for iADRS and CDR-SB scores; the lack of direct assessment of the effect of donanemab on patient HRQoL and caregiver burden; substantial missing data; and methodological limitations associated with evaluating long-term cognitive decline through comparisons of CDR-SB scores between patients treated with donanemab and an external Alzheimer’s Disease Neuroimaging Initiative cohort.

CDEC acknowledged that patients identified a need for disease-modifying therapies with acceptable safety profiles that maintain or prolong independence, preserve HRQoL, support cognitive function, slow or halt disease progression, and prevent memory loss. The committee noted that iADRS and CDR-SB outcomes of the TRAILBLAZER-ALZ 2 trial, as well as other measures of cognition and function, consistently favoured donanemab and were considered clinically meaningful for patients with early AD by the clinical experts consulted by CDA-AMC. CDEC determined that the reviewed evidence indicates that donanemab addresses some of the needs identified by patients by slowing cognitive and functional decline. However, uncertainty remains regarding the effects of donanemab on patient HRQoL, independence, and caregiver burden because these outcomes were not directly assessed in the submitted evidence. CDEC concluded that the totality of evidence demonstrates that donanemab addresses a significant unmet clinical need in patients with early AD and confirmed amyloid pathology who are APOE4 noncarriers or heterozygotes.

Further information on the committee’s discussion around clinical value is provided in the Summary of Deliberation section.

Developing the Recommendation

The determination of acceptable clinical value was sufficient for CDEC to recommend reimbursement of donanemab. As part of the deliberation on whether to recommend reimbursement, the committee also considered unmet clinical need, unmet nonclinical need, and health inequity. Information on this discussion is provided in the Unmet Clinical Need and Distinct Social and Ethical Considerations domains in the Summary of Deliberation section.

Because CDEC recommended that donanemab be reimbursed, the committee also deliberated on whether reimbursement conditions should be added to address important economic considerations, health system impacts, or social and ethical considerations, or to ensure clinical value is realized. The resulting reimbursement conditions, with accompanying reasons and implementation guidance, are stated in Table 1.

Summary of Deliberation

CDEC considered all domains of value of the deliberative framework before developing its recommendation: clinical value, unmet clinical need, distinct social and ethical considerations, economic considerations, and impacts on health systems. For further information on the domains of value, refer to Expert Committee Deliberation at Canada’s Drug Agency.

The committee considered the following key discussion points, organized by the 5 domains of value.

Clinical Value

• Appropriate comparators: At the time the submission was received, there were no disease-modifying therapies for AD that were reimbursed by public drug plans or that had received a recommendation to reimburse from CDEC. Given this, placebo plus BSC (including symptomatic medications for AD) was considered an appropriate comparator for donanemab plus BSC.

• Efficacy versus placebo: Evidence from 1 randomized, controlled, phase III trial (the TRAILBLAZER-ALZ 2 trial) demonstrated that in adult patients with MCI or mild dementia due to AD and confirmed amyloid pathology who were APOE4 heterozygotes or noncarriers, treatment with donanemab resulted in less cognitive and functional decline compared to placebo, as measured by iADRS and CDR-SB scores. For iADRS scores (primary end point), the between-group difference in the mean change from baseline to week 76 was 3.38 points (95% CI, 1.832 points to 4.924 points; P < 0.001) in favour of donanemab. iADRS scores range from 0 to 144 points, with lower scores indicating greater impairment. The committee noted that the iADRS tool was developed by the sponsor and that evidence on the validity and reliability of this outcome measure from sources external to the sponsor were not identified. For CDR-SB scores (secondary end point), the between-group difference in the mean change from baseline to week 76 was −0.77 points (95% CI, −1.04 points to −0.49 points; P < 0.001) in favour of donanemab. CDR-SB scores range from 0 to 18, with higher scores indicating greater impairment. CDEC noted that although the CDR-SB is a well-established and validated questionnaire in patients with early AD, it does not have a clearly defined between-group MID. Results for other end points evaluating cognition or function in the trial (i.e., ADAS-Cog13, ADCS-iADL, and MMSE scores) were consistent with iADRS and CDR-SB results in showing less cognitive and functional decline with donanemab compared with placebo.

• Clinical importance of treatment effects: The committee reviewed input from the patient groups, clinician groups, and clinical experts consulted for this review that indicated the key goals in the treatment of patients with early AD are to halt or slow disease progression; maintain cognition, functional capacity, and independence; prevent memory loss; maintain quality of life; and reduce caregiver burden and the impact on caregivers’ own quality of life. Based on the submitted efficacy evidence, CDEC concluded that donanemab is a disease-modifying therapy that addresses an unmet clinical need in patients with early AD by reducing cognitive and functional decline.

• Certainty of the evidence: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to rate the certainty of the iADRS and CDR-SB outcomes from the TRAILBLAZER-ALZ 2 trial in the indicated population. The committee noted that the absence of a published or estimated between-group MID for iADRS scores was a limitation that caused rating down for serious imprecision, resulting in moderate certainty in the evidence for this outcome; the absence of a MID presented challenges in assessing the certainty in the clinical meaningfulness of the treatment effect. However, CDEC considered input from the clinical experts consulted by CDA-AMC who generally agreed that the iADRS findings were clinically meaningful. CDEC noted that the GRADE assessment for CDR-SB applied a between-group MID of 0.5 points, which CDA‑AMC implemented based on published within-group MID estimates for the scale and input from clinical experts, who indicated that a 0.5-point difference is clinically meaningful in patients with early AD. Using this threshold, the certainty of the evidence for CDR-SB was rated as high.

• Long-term efficacy: CDEC reviewed analyses comparing changes from baseline in CDR-SB scores among patients treated with donanemab during the core and LTE phases of the TRAILBLAZER-ALZ 2 study with those of an external cohort from the Alzheimer’s Disease Neuroimaging Initiative. The results favoured donanemab, with between-group differences in change from baseline in CDR-SB scores of −0.6 points (95% CI, −0.9 points to −0.2 points) at 18 months and −1.0 point (95% CI, −1.5 points to −0.4 points) at 36 months. These findings suggest that the effect of donanemab in slowing cognitive and functional decline may persist beyond the 18-month core trial period compared with modelled natural disease progression. However, CDEC noted considerable uncertainty in these results due to the lack of a randomized comparator, reliance on an external control cohort, small effective sample sizes, incomplete statistical reporting, and resulting uncertainty in the estimated treatment effects.

• Harms findings: CDEC noted that evidence of moderate certainty from the TRAILBLAZER-ALZ 2 trial demonstrated that, compared with placebo, donanemab was associated with higher rates of SAEs, ARIA-E events, and ARIA-H events. Notably, ARIA-E and ARIA-H events occurred more frequently in the donanemab group than in the placebo group, with ARIA-E events reported in 20.6% versus 1.8% of patients and ARIA-H events reported in 27.6% versus 12.2% of patients, respectively. The committee discussed that ARIA events occurred primarily during the first 24 weeks of treatment and that limited access to MRI in some jurisdictions may pose challenges for monitoring. CDEC also reviewed safety data from the TRAILBLAZER-ALZ 2 LTE study, which were generally consistent with those observed in the core trial and did not identify any new safety signals, although interpretation was limited by the absence of a control group and the potential for selective attrition. While recognizing that the safety profile of donanemab is an important consideration, CDEC noted that early AD is a progressive and debilitating condition with limited treatment options and emphasized the importance of informed patient decision-making regarding the potential benefits and risks of treatment.

• Health Canada–approved dosing: CDEC discussed that the donanemab dosing regimen used in the TRAILBLAZER-ALZ 2 trials differs from the Health Canada–approved regimen, which recommends a more gradual titration during the first 3 doses. The committee reviewed evidence from the TRAILBLAZER-ALZ 6 phase IIIb trial, a multicentre, randomized, double-blind study, which demonstrated that the Health Canada–approved regimen was associated with a lower frequency of ARIA-E events than the standard dosing regimen used in the TRAILBLAZER-ALZ 2 trial while maintaining comparable donanemab exposure and pharmacodynamic effects on amyloid plaque reduction.

• Gaps in the available evidence: CDEC noted that patients and clinicians identified HRQoL and caregiver burden as important outcomes in the treatment of AD. However, these outcomes could not be evaluated because the sponsor did not provide evidence on the effects of donanemab on patient HRQoL or caregiver burden. The committee also noted that the CDA-AMC review was based primarily on evidence from a placebo-controlled trial and that no comparative evidence (direct or indirect) with another disease-modifying therapy was reviewed. However, CDEC considered the placebo-controlled evidence acceptable because, at the time of the review, no disease-modifying therapies met the relevant comparator designation under the CDA‑AMC reimbursement review procedures.

• Clinical value: Based on the submitted evidence and all the preceding considerations, CDEC considered that donanemab has acceptable clinical value compared with BSC in adult patients with a clinical diagnosis of MCI or mild dementia due to AD, who are APOE4 heterozygotes or noncarriers, and who have confirmed amyloid pathology.

Unmet Clinical Need

• Input on unmet clinical need: Patients and clinicians identified a need for accessible, publicly reimbursed, disease-modifying treatments for early AD (including MCI) that can maintain, or slow declines in, cognition, function, and independence.

• Severity of the disease: CDEC discussed that AD is a progressive and irreversible neurodegenerative disorder, characterized by worsening cognitive decline, functional impairment, significant psychological and behavioural symptoms, and loss of independence and identity. AD ultimately leads to complete dependence and has substantial impacts on patients’ HRQoL and caregiver and family burden.

• Availability of treatment options: The current pharmacologic treatments for MCI or mild dementia due to AD are acetylcholinesterase inhibitors (i.e., donepezil, galantamine, and rivastigmine) and lecanemab. Memantine is an available treatment for AD but is only approved for the treatment of moderate to severe disease. The clinical experts consulted by CDA‑AMC noted that acetylcholinesterase inhibitors are symptomatic therapies that provide only temporary and modest improvements, are associated with adverse effects, do not alter the course of the disease, and are not approved for the treatment of MCI. Lecanemab is a disease-modifying therapy indicated for MCI and mild dementia stages of AD, but it is not currently publicly reimbursed and therefore is not widely accessible.

Distinct Social and Ethical Considerations

• Input on unmet nonclinical need: The committee acknowledged patient group input indicating serious physical and psychological burdens associated with caregiving and the financial strain faced by many caregivers due to the need to decrease work hours or leave the workforce altogether. CDEC noted that uncertainty regarding the effects of donanemab on caregiver burden and caregiver quality of life remains an important evidence gap because these outcomes were not directly evaluated in the submitted evidence.

• Equity considerations: CDEC acknowledged existing disparities in timely diagnosis and access to care experienced by many systemically marginalized and equity-deserving groups. In particular, they discussed challenges faced by Indigenous Peoples, populations with low incomes, and those living in rural or remote locations with limited access to specialized care and increased financial burdens associated with travel. They discussed the possibility that donanemab may exacerbate disparities in AD care for some given the additional requirements associated with treatment initiation, administration, and monitoring (i.e., accessing specialized care, confirmation of amyloid pathology, APOE4 testing, infusion schedule, and MRI monitoring). The committee also considered the limited racial and ethnic diversity of the TRAILBLAZER-ALZ 2 trial population and resulting uncertainty regarding benefits and harms across diverse populations.

• Ethical implications: CDEC discussed the importance of shared decision-making given the potential benefits, risks, treatment burdens, and uncertainties associated with donanemab. This includes ensuring realistic expectations by considering whether the potential degree of slowing disease progression is meaningful to an individual patient in light of their own goals, their understanding of treatment burden, and their tolerance for risk of experiencing SAEs such as ARIAs. They also discussed how the implementation of donanemab would require expanding and reorganizing health system resource capacity in Canada to support timely, safe, appropriate, and equitable access.

Economic Considerations

• Health impacts of donanemab versus relevant comparators: Based on the evidence reviewed for this submission, donanemab plus BSC is predicted to be associated with a gain of 0.35 life-years compared to BSC alone and may result in a gain of 0.44 quality-adjusted life-years (QALYs) compared to BSC over a lifetime (27-year) horizon.

• Cost of donanemab versus relevant comparators: Donanemab plus BSC is predicted to be associated with higher costs to the health care system than BSC alone (incremental costs = $59,480) over a lifetime (27-year) horizon, primarily driven by increased costs associated with donanemab treatment (i.e., drug acquisition, administration, diagnostic testing, and AEs).

• Key findings of the economic evaluation: The incremental cost-effectiveness ratio (ICER) of donanemab plus BSC compared to BSC alone was $136,669 per QALY gained in the CDA-AMC base case adopting a health care payer perspective. The estimated ICER was sensitive to treatment effect waning assumptions and the starting disease severity of patients. If considering a societal perspective that includes out-of-pocket costs and caregiver HRQoL impacts, the ICER of donanemab plus BSC compared to BSC alone was $128,612 per QALY gained.

  Figure 1: Estimate of the ICER Used by CDEC to Inform the Price Condition

  

  CDEC = Canadian Drug Expert Committee; ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year.

• Certainty of the evidence: As donanemab is associated with a fixed treatment duration of 18 months, a substantial portion of health benefits are largely driven by assuming a sustained treatment benefit beyond the 18-month treatment course. CDEC noted that given the absence of long-term clinical evidence beyond 3 years, the effect of donanemab following treatment discontinuation remains highly uncertain and additional price reductions may be required.

• Societal value: The committee discussed that treatment with donanemab may have an important impact on societal considerations such as caregiver HRQoL and out-of-pocket costs. Thus, CDA-AMC presented a cost-effectiveness analysis adopting a societal perspective that included these outcomes. The committee agreed that there was sufficient evidence to support that there may be an impact of donanemab on caregiver HRQoL and out-of-pocket costs.

• Other considerations: CDEC also discussed that while lecanemab was not publicly reimbursed at the time of this review, if lecanemab were to be publicly funded, the cost-effectiveness of donanemab compared to lecanemab is unknown and it is uncertain how the introduction of lecanemab will affect market share expectations and subsequently the budget impact of donanemab.

Impacts on Health Systems

• Anticipated budget impact: CDA-AMC estimated that 36,319 patients would be eligible for donanemab plus BSC over a 3-year period (year 1 = 7,578; year 2 = 11,600; year 3 = 17,141), of whom 16,822 would be expected to receive donanemab plus BSC (year 1 = 3,031; year 2 = 5,220; year 3 = 8,570). The estimated incremental budget impact of reimbursing donanemab plus BSC is predicted to be approximately $642 million over the first 3 years, with an expected expenditure of $644 million on donanemab alone. The actual budget impact of reimbursing donanemab will depend on the number of patients eligible for treatment, which is influenced by access to clinical assessments and diagnostic testing (which were uncertain in the budget impact analysis).

• Organizational implications: CDEC discussed that confirmation of amyloid pathology is required for initiation of treatment with donanemab. The committee discussed that there are disparities in amyloid PET access and variability in reimbursement of amyloid PET and cerebrospinal fluid and blood-based AD biomarker testing across jurisdictions in Canada, which leads to inequities in access. CDEC also discussed training requirements related to infusion administration, tools for patient assessment and evaluation of treatment response, and safety monitoring. CDEC noted input from the clinical experts regarding the need for close monitoring for ARIA events and the MRI monitoring requirements stated in the donanemab product monograph. The committee discussed MRI capacity constraints that exist in various provinces and territories across the country, including limited and variable access to MRI, which may pose challenges for safe and equitable treatment initiation, and adequate and timely monitoring for all eligible patients. System capacity constraints along the continuum of care for AD raise questions about who will be responsible for prioritizing eligible patients for access to treatment and supporting infrastructures. The committee also considered that a 10-minute MRI sequence can screen for ARIAs, which could help mitigate capacity constraints. The committee noted concerns regarding current resources and that health care system changes would be required to accommodate the required monitoring, and that MRI capacity remains a practical consideration across jurisdictions. CDEC also discussed discontinuation of donanemab based on amyloid plaque clearance. The committee noted that in the TRAILBLAZER-ALZ 2 trial, patients whose amyloid plaque levels met certain criteria, as measured by amyloid PET performed at 24 weeks and 52 weeks, discontinued treatment with donanemab. CDEC noted input from the clinical experts that this currently would not be feasible in routine clinical practice in Canada due to the variability in, and limited access to, PET scans across the country.

• Equity considerations: CDEC noted current systems-level gaps in AD diagnosis, care, and management in Canada. The committee also noted how these gaps tend to be exacerbated for those living in rural or remote areas and for racialized and other equity-deserving groups. The committee discussed how the implementation of donanemab would require expanding and reorganizing health system resource capacity in Canada to support timely, safe, appropriate, and equitable access. The committee discussed the principle of proportionality in relation to the balance of benefits and harms of donanemab, and they noted relevant health system challenges that should inform system-level planning. They also discussed the overall limited population of patients with MCI or mild dementia due to AD who would be eligible for treatment with donanemab as well as resource allocation challenges associated with providing this therapy alongside meeting the needs of those who are ineligible. CDEC also discussed health system capacity considerations and the potential for the implementation of donanemab to affect resources and timely access to care for other patients and conditions.

• Testing procedure considerations: APOE genotype testing is not currently performed as part of routine testing for patients with early AD in Canada. Because the testing infrastructure for APOE genotype testing is already established, additional medically necessary indications in Canada for APOE genotyping, including anti–amyloid-beta treatment eligibility and ARIA risk assessment, would be feasible and would not likely significantly impact human or health care resources.

• Need for real-world evidence generation: CDEC noted that important uncertainties remain regarding the long-term effectiveness, safety, utilization patterns, and health system impacts of donanemab. The committee discussed that clinical trial follow-up remains limited, particularly after treatment discontinuation, and that the real-world implications of treatment on cognitive outcomes, functional outcomes, caregiver burden, health care resource utilization, and ARIA monitoring remain uncertain. As such, CDEC considered the development of a sponsor-supported registry to be valuable for collecting real-world evidence and informing future assessments of clinical outcomes, safety, and system impact.

Sources of Information Used by the Committee

To make its recommendation, the committee considered the following information (links to the full documents for the review can be found on the project web page):

• the CDA-AMC review of the clinical and pharmacoeconomic evidence submitted by the sponsor, as well as relevant ethical issues and potential impacts of testing procedures related to donanemab (refer to the Main Report and the Supplemental Material document)

• the sponsor’s comments on the draft report and the CDA-AMC responses

• patients’ perspectives gathered by 4 patient groups, the Alzheimer Society of Canada, the Alzheimer Society of Ontario, the International Federation on Ageing, and Dementia Network Calgary (refer to the Patient and Clinician Group Input document)

• input from a person with lived experience who delivered a brief presentation and answered questions from the committee (refer to the Person With Lived Experience section earlier in this document)

• input from 7 clinician groups, the Cognitive Neurosciences Clinic (University of Calgary), the Covenant Community Health Centre Lakewood, the Douglas Mental Health University Institute Memory Clinic (Montréal, Quebec), Trillium Health Partners, the University of British Columbia Hospital Clinic for Alzheimers and Related Disorders, the CCNA, and the Consortium of Canadian Centres for Clinical Cognitive Research (refer to the Patient and Clinician Group Input document)

• input from public drug programs that participate in the reimbursement review process (refer to the Supplemental Material document)

• input from 7 clinical experts with expertise in the management of AD consulted by CDA-AMC.

Special thanks: CDA-AMC extends special thanks to the individual who presented directly to CDEC and to the patient group representing the community of those living with AD, including David Black and the Engagement of People with Lived Experience of Dementia (EPLED) program of the CCNA.

General note: CDA-AMC makes every attempt to engage with people with lived experience as closely to the indication under review as possible; however, at times, CDA-AMC is unable to do so and instead engages with individuals with similar treatment journeys to ensure lived experience perspectives are included and considered in Reimbursement Reviews. CDA-AMC is fortunate to be able to engage with individuals who are willing to share their treatment journeys with CDEC.

CDEC Information

Members of the Committee

Dr. Peter Jamieson (Chair), Dr. Kerry Mansell (Vice-Chair), Sally Bean, Daryl Bell, Dan Dunsky, Dr. Ran Goldman, Dr. Trudy Huyghebaert, Dr. Dennis Ko, Dr. Christine Leong, Alicia McCallum, Dr. Srinivas Murthy, Dr. Nicholas Myers, Dr. Krishnan Ramanathan, Dr. Marco Solmi, Carla Velastegui, Dr. Edward Xie, and Dr. Peter Zed.

Meeting date: August 27, 2026

Regrets: Two expert committee members did not attend.

Conflicts of interest: None