Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease in the US

Ross, E. Clarke; Weinberg, Marc S.; Arnold, Steven E.

doi:10.1001/jamaneurol.2022.0315

“…For example, the US Food and Drug Administration approved a new amyloid beta-directed antibody aducanumab (Aduhelm; BiogenInc) for treating AD recently in July 2021 [ 39 ]. The cost-effectiveness of aducanumab compared to current standard care can depend largely on the pricing of drug and requires intensive research [ 40 ]. Study designs of further studies should also be improved with non-industrial sponsorships, long-term follow-ups, reliable measurements in HRQoL of patients, and cost collection from both healthcare and societal perspectives.…”

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness of pharmacological therapies for people with Alzheimer’s disease and other dementias: a systematic review and meta-analysis

Huo

¹

,

Lin

²

,

Bat

³

et al. 2022

Cost Eff Resour Alloc

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Objectives This study aims to synthesize the empirical economic evidence of pharmaceutical therapies for people with dementia. Study design Systematic review and meta-analysis. Literature evaluating the costs and effects of drug therapies for dementia was indexed until December 2021. Quality of study was assessed using the Cochrane Risk of Bias Tool and Consensus on Health Economic Criteria list. Cost data were standardized to 2020 US dollars and analyzed from healthcare service and societal perspectives. Random-effects models were used to synthesize economic and clinical data, based on mean differences (MDs) and standardized MDs. Results Ten unique studies were identified from 11,771 records. Acetylcholinesterase inhibitors (AChEIs) and memantine improved dementia-related symptoms, alongside nonsignificant savings in societal cost (AChEIs: MD-2002 [− 4944 ~ 939]; memantine: MD-6322 [− 14355 ~ 1711]). Despite decreases in cost, antidepressants of mirtazapine and sertraline and second-generation antipsychotics were limited by their significant side effects on patients’ cognitive and activity functions. Subgroup analysis indicated that the impacts of AChEIs on cost were affected by different analytical perspectives, follow-up periods, and participant age. Conclusions AChEIs and memantine are cost-effective with improvements in dementia-related symptoms and trends of cost-savings. More empirical evidence with non-industrial sponsorships and rigorous design in different settings is warranted.

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“…Part of the discrepancy is the low estimate of a treatment effect by Ross et al of 0.11, but another component is the erroneous interpretation of their source for QALY loss with disease severity. Their source, Neumann et al, indeed reports the QALYs for patients with mild, moderate, and severe dementia that the authors used.…”

mentioning

confidence: 99%

“…To the Editor In their recent article “Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease in the US,” Ross et al provide much needed insights into an important question given the potentially large treatment-eligible population and the expected budget impact of an Alzheimer treatment. However, their analysis has several methodologic flaws that may lead them to understate the value of such treatments.…”

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confidence: 99%

Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease—Estimating the True Value

Mattke

¹

2022

JAMA Neurol

1

0

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To the Editor Alzheimer disease (AD) can be clinically devastating and costly, given its potential to profoundly impair quality of life and activities of daily living. Ross et al 1 sought to evaluate cost-effectiveness of controversial novel antiamyloid monoclonal antibodies aducanumab and donanemab, which aim to slow AD progression. The US Food and Drug Administration (FDA), despite dissent of its expert advisory committee, approved aducanumab under the accelerated approval pathway in 2021, based on the surrogate end point of reduction in cerebral amyloid-β plaque, and is currently considering donanemab for accelerated approval on similar grounds.Fundamentally, a drug that is not effective cannot be cost-effective. Thus, engaging in and publishing costeffectiveness analyses (CEAs) of an unproven class of drugs lends them undue legitimacy. In designing this model, the authors used clinical outcomes to calculate model efficacy, as described in quality-adjusted life-years. Dementia stages were assigned utility values and state transitions were based on changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) and Mini-Mental State Examination (MMSE) over the course of the trials. 1 However, the clinical outcomes from the 2 phase 3 aducanumab trials are discordant and statistically insignificant by meta-analysis, emphasizing that the efficacy of aducanumab remains unclear, as the FDA also acknowledges. 2 Similarly, the authors conclude that donanemab would be cost-effective at a price of $20 000 per year, based on a single, phase 2 trial that found a 3.2-point between-group difference in the integrated Alzheimer's Disease Rating Scale, a score out of 144 points. 3 However, this trial showed no difference between the donanemab and control groups in MMSE or CDR-SB. 3 The discordance between cognitive assessment tools seen with both drugs further undermines whether either drug is having a clinically significant effect. This uncertainty is not reflected in this model nor this cost-effective price of $20 000. The authors further comment that donanemab's timelimited dosing scheme may improve the cost-effectiveness of all antiamyloid drugs, yet this notion rests on the contested amyloid cascade hypothesis: that lowering amyloid will slow progression of AD. 4,5 Although decision-science approaches can be useful to determine the value of gathering further information, this is not formally quantified by the authors, although the US Centers for Medicare and Medicaid has already recognized the value of further information in their decision to fund aducanumab only for patients in clinical trials. We question the appropriateness of a cost-effectiveness analysis before demonstration of a therapy's effectiveness.

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“…To the Editor Alzheimer disease (AD) can be clinically devastating and costly, given its potential to profoundly impair quality of life and activities of daily living. Ross et al sought to evaluate cost-effectiveness of controversial novel antiamyloid monoclonal antibodies aducanumab and donanemab, which aim to slow AD progression. The US Food and Drug Administration (FDA), despite dissent of its expert advisory committee, approved aducanumab under the accelerated approval pathway in 2021, based on the surrogate end point of reduction in cerebral amyloid-β plaque, and is currently considering donanemab for accelerated approval on similar grounds.…”

mentioning

confidence: 99%

“…In designing this model, the authors used clinical outcomes to calculate model efficacy, as described in quality-adjusted life-years. Dementia stages were assigned utility values and state transitions were based on changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) and Mini-Mental State Examination (MMSE) over the course of the trials . However, the clinical outcomes from the 2 phase 3 aducanumab trials are discordant and statistically insignificant by meta-analysis, emphasizing that the efficacy of aducanumab remains unclear, as the FDA also acknowledges …”

mentioning

confidence: 99%

Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease—Estimating the True Value

Cliff

¹

,

Kelkar

²

2022

JAMA Neurol

2

0

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To the Editor Alzheimer disease (AD) can be clinically devastating and costly, given its potential to profoundly impair quality of life and activities of daily living. Ross et al 1 sought to evaluate cost-effectiveness of controversial novel antiamyloid monoclonal antibodies aducanumab and donanemab, which aim to slow AD progression. The US Food and Drug Administration (FDA), despite dissent of its expert advisory committee, approved aducanumab under the accelerated approval pathway in 2021, based on the surrogate end point of reduction in cerebral amyloid-β plaque, and is currently considering donanemab for accelerated approval on similar grounds.Fundamentally, a drug that is not effective cannot be cost-effective. Thus, engaging in and publishing costeffectiveness analyses (CEAs) of an unproven class of drugs lends them undue legitimacy. In designing this model, the authors used clinical outcomes to calculate model efficacy, as described in quality-adjusted life-years. Dementia stages were assigned utility values and state transitions were based on changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) and Mini-Mental State Examination (MMSE) over the course of the trials. 1 However, the clinical outcomes from the 2 phase 3 aducanumab trials are discordant and statistically insignificant by meta-analysis, emphasizing that the efficacy of aducanumab remains unclear, as the FDA also acknowledges. 2 Similarly, the authors conclude that donanemab would be cost-effective at a price of $20 000 per year, based on a single, phase 2 trial that found a 3.2-point between-group difference in the integrated Alzheimer's Disease Rating Scale, a score out of 144 points. 3 However, this trial showed no difference between the donanemab and control groups in MMSE or CDR-SB. 3 The discordance between cognitive assessment tools seen with both drugs further undermines whether either drug is having a clinically significant effect. This uncertainty is not reflected in this model nor this cost-effective price of $20 000. The authors further comment that donanemab's timelimited dosing scheme may improve the cost-effectiveness of all antiamyloid drugs, yet this notion rests on the contested amyloid cascade hypothesis: that lowering amyloid will slow progression of AD. 4,5 Although decision-science approaches can be useful to determine the value of gathering further information, this is not formally quantified by the authors, although the US Centers for Medicare and Medicaid has already recognized the value of further information in their decision to fund aducanumab only for patients in clinical trials. We question the appropriateness of a cost-effectiveness analysis before demonstration of a therapy's effectiveness.

show abstract

Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease in the US

Cited by 53 publications

References 63 publications

Cost-effectiveness of pharmacological therapies for people with Alzheimer’s disease and other dementias: a systematic review and meta-analysis

Cost-effectiveness of pharmacological therapies for people with Alzheimer’s disease and other dementias: a systematic review and meta-analysis

Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease—Estimating the True Value

Cost-effectiveness of Aducanumab and Donanemab for Early Alzheimer Disease—Estimating the True Value

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