Aduhelm Approval Brings Potential for an Evolving Alzheimer’s Disease Treatment Market and Challenges for Healthcare Costs
On June 7th, the FDA granted accelerated approval for Biogen’s amyloid beta-directed anti-body Aduhelm (aducanumab), the first potentially disease-modifying treatment and first approval for Alzheimer’s disease (AD) in nearly two decades. The approval brings new hope for patients, in addition to uncertainties within the medical community and healthcare budget impact concerns.[1]
Accelerated approval is typically granted for products that treat serious conditions and fulfill an unmet need. The accelerated approval for Aduhelm requires Biogen to conduct a Phase IV follow-up study to confirm effectiveness, expected to be completed by 2030 – if the study fails, Aduhelm may be pulled from the market.[1,2] As the study read-out is almost a decade away, there may also be opportunity for Biogen to collect read-world evidence to determine Aduhelm’s efficacy outside clinical trials.
The road to approval has been long for Aduhelm, and its current approval is based on a surrogate endpoint (amyloid plaque destruction). It is “reasonably likely to predict clinical benefit” but has not been conclusively linked to patient-relevant outcomes, such as cognitive and functional ability that are key for AD patients.[3,4] Biogen initially halted two trials with disappointing results in 2019, but restarted both with higher doses after a post-hoc analysis and consultation with the FDA. Additionally, in November 2020, an FDA advisory panel rejected the drug based on conflicting efficacies, as patients had a modest improvement in dementia symptoms in one trial, but those on aducanumab fared worse compared with placebo. [1,2]
There is concern that the approval based on a surrogate endpoint lowers the bar and sets a precedent for other treatments of uncertain benefit. [1,4] Aduhelm was developed to treat patients with mild cases of cognitive impairment or dementia and efficacy has not been demonstrated in a broader population, while the FDA’s approval does not specify the specific population eligible for treatment. [5]
In addition to uncertain benefit, Aduhelm’s price of $4,312 per infusion for a patient of average weight, or $56,000 per year*, has also sparked backlash, especially in the context of a mostly Medicare population, some of whom will have to pay $11,500 out-of-pocket cost for one year of coinsurance while using the drug. [5] The Institute for Clinical and Economic Review (ICER), has previously stated the cost-effective recommended price for Aduhelm to be $2,500-8,300 per year, given the “insufficient” clinical trial evidence. [7] Biogen’s argument is the high unmet need and cost that AD and dementia pose a major burden on the US healthcare system – around $250 billion annually for conditions that affect over 6 million Americans, with cases and spending expected to double by 2050. [4,7] The argument is only valid if Biogen can demonstrate an improvement in cognitive and functional ability and a corresponding reduction in some of these healthcare costs. Cost-offsets data is currently lacking, and it is unclear if Aduhelm will be able to reduce healthcare costs in the real-world, alongside dispelling patient benefit uncertainties.
Note: * Average weight assumed at 77kg, price assumption assumes vial splitting is allowed.
Marketing Authorization Application
The marketing authorization application for Aduhelm has been accepted by the European Medicines Agency (EMA) last November, and its decision is still pending. [9] In line with the FDA approval, if EMA approval is granted, it is expected to be with the requirement to provide the Phase IV study data. The high unmet need and data uncertainties make Aduhelm a good candidate for outcomes-based agreements through reimbursement with evidence development in some European markets. In fact, Biogen has already entered into an outcomes-based agreement with Cigna Corporation in the US, and a similar strategy is anticipated in Europe. [10] Price-volume agreements may also be required in some markets, such as France, given the high budget impact concern. Reimbursement is likely to also come with population restrictions to limit prescription to those patients who meet the clinical trial inclusion / exclusion criteria trial population in many markets, in line with how some US private plans such as Cigna, expect to cover the product. [6] Biogen’s pricing strategy for ex-US markets, however, will also be a key variable, and remains to be seen.
The AD and dementia market is expected to further grow as potentially disease-modifying treatments for AD with similar mechanisms of action already in the pipeline - Eli Lilly’s donanemab, Roche’s gantenerumab, Pfizer and Johnson & Johnson’s bapineuzumab, and Eisei’s lecanemab. [3,4] They are likely to face similar challenges to Aduhelm. They should aim to demonstrate robust efficacy in patient-related outcomes, as well as cost-offsets, to gain approval and reimbursement, as well as to compete in the new evolving space.
Windrose’s Take:
Aduhelm represents a modest improvement, but is a major step forward in a disease area with a very high unmet need and characterized by several drug failures
Although the price certainly exceeds ICER’s assessments of a cost-effective price based on the available data, and raises patient and healthcare affordability concerns, the list price appears to be in line with other “disease-modifying” drugs in neurology, such as Ocrevus, Tecfidera, and Tysabri for multiple sclerosis
The price could potentially be justified if Aduhelm can delay the progression of the disease for some patients even by a year or two, given the significant cost and quality of life burden of Alzheimer's disease
While Aduhelm’s innovation is incremental, it is important as many manufacturers have stopped investing in Alzheimer’s disease, despite significant unmet needs
Breakthrough innovation is sometimes achieved through incremental improvements, so we hope that the approval of this product will reignite investment in this important disease area
Article written by Elizaveta Tchebaniouk, Senior Analyst Windrose Consulting Group