Estimated cost-effectiveness of anti-amyloid monoclonal antibodies

All of the anti-amyloid monoclonal antibodies currently approved (Aduhelm) or in phase 3 clinical trials (donanemab, lecanumab, and gantenerumab) are effective at removing beta-amyloid from the brain, but effects so far on slowing cognitive decline in early-stage Alzheimer’s disease have been relatively small if present at all. A recent paper in JAMA Neurology compares estimates of cost-effectiveness of two of these, Aduhelm, aka aducanumab, and donanemab, currently undergoing several phase 3 trials. Donanemab is even more effective than Aduhelm in removing amyloid from the brain, and in the current phase 3 trials, treatment is stopped once amyloid is removed, unlike Aduhelm which requires ongoing treatment. The authors used a decision-analytic model of Alzheimer’s treatment, incorporating published data on Alzheimer’s natural history, its health care and societal costs, and the efficacy and adverse effects of anti–amyloid antibody treatments to estimate cost-effectiveness. The findings suggest “that at their current expected prices [$25,000 per year], neither aducanumab nor donanemab would be cost-effective for the treatment of early AD in the US. Although aducanumab’s price would need to fall to less than $3000/y to become cost-effective, donanemab—if its efficacy is confirmed in phase 3 trials—could be cost-effective when priced at $20,000/y. The limited-duration dosing scheme used with donanemab [drug is stopped as soon as amyloid becomes undetectable] is critical to its greater health-economic value; this approach may provide a rubric by which sufficiently effective anti-amyloid drugs could be economically viable in the US health care system, even when priced comparably to other biologics.” 

Despite the furor over the controversial FDA approval of Aduhelm, I haven’t given up on this class of drugs. The anti-amyloid monoclonal antibodies may yet be shown to be effective at slowing cognitive decline in some people with Alzheimer’s disease. For example, they may work better on the pre-symptomatic stage of Alzheimer’s, before too many neurons have died off. Phase 3 trials testing this hypothesis are currently under way for donanemab and gantenerumab. There are hints that APOE-4 carriers may get a better response to these drugs, but on the other hand these APOE-4 carriers are more likely to have the ARIA side effects of swelling and/or bleeding in the brain. Perhaps having ARIA is a prerequisite for having an effective response.  This possibility is not as outlandish as it might seem and is worth a post of its own at a later time. Once we have identified drugs that are effective and safe, we should ask at what price point will they be cost-effective? It will undoubtedly take time and careful clinical trials to sort this all out.