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July 31, 2023

Are New Alzheimer Drugs Better Than Older Drugs?

Author Affiliations
  • 1Georgetown University Medical Center, Washington, DC
  • 2Department of Pharmacology and Physiology, Department of Family Medicine, Georgetown University Medical Center, Washington, DC
JAMA Intern Med. 2023;183(9):902-903. doi:10.1001/jamainternmed.2023.3061

In July 2023, the US Food and Drug Administration (FDA) provided full approval for an amyloid-β–directed antibody, lecanemab (Leqembi), for treating Alzheimer disease. The prescribing information states that treatment, which is administered as an intravenous infusion, should be initiated in patients with mild cognitive impairment or the mild dementia stage of the disease, which is the population in which the treatment was studied in clinical trials. Lecanemab is the second monoclonal antibody targeting β-amyloid protein to be approved; the first was aducanumab (Aduhelm) in 2021. The FDA approved lecanemab via its accelerated approval program in January 2023 based solely on the decline in β-amyloid as estimated on positron emission tomography scans in the brains of patients taking the drug compared with placebo. The agency granted full approval of lecanemab based on clinical efficacy data from a clinical trial with 1795 participants.1 Advocacy groups were pressuring the US Centers for Medicare & Medicaid Services to pay for the drug.

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4 Comments for this article
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A very cogent summary!
David Karpf, MD | Stanford University School of Medicine
The review entitled "Are New Alzheimer Drugs Better Than Older Drugs?" provides convincing arguments in support of the conclusion that newer Alzheimer Disease drugs are not meaningfully better than older Alzheimer Disease drugs, and reasonably convincing arguments that neither class of drugs provides clinically meaningful benefits. And convinces me, at least, that the new drugs should not be routinely prescribed nor universally reimbursed.
CONFLICT OF INTEREST: None Reported
Great article
Simret Nanda, M.D | Simret Nanda, M.D.
I totally agree in reducting modifiable lifestyle risk factors first before spending money on these new medicines that barely work.
CONFLICT OF INTEREST: None Reported
Bull's eye
Wietse Wiels, MD | OLV Hospital
I commend the authors on this crystal clear, commonsensical yet thorougly scientific take on the AD drug issues.

Even if one should always try to avoid positing false dichotomies, it is truly worrying how industry, advocacy groups and above all AD researchers are pressuring public opinion to applaud the emperor's new clothes.

And this while, as the authors point out, more powerful and cheap interventions are already available. For the price of these drugs and their logistical consequences, one might as well distribute free hearing aids and access to sports or social facilities to half of
our ageing citizens.
CONFLICT OF INTEREST: None Reported
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AD immunotherapy
Markku Kurkinen, PhD | NeuroActiva, San Jose, California, USA
In evaluating the clinical benefit of anti-amyloid antibodies in the treatment of AD patients the control group should be receiving the standard treatment of memantine, donepezil or galantamine [1.2], and not placebo saline solution.

1. Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A, Barber R, Burns A, Dening T, Findlay D, Holmes C, Hughes A, Jacoby R, Jones R, Jones R, McKeith I, Macharouthu A, O’Brien J, Passmore P, Sheehan B, Juszczak E, Katona C, Hills R, Knapp M, Ballard C, Brown R, Banerjee S, Onions C, Griffin M, Adams J, Gray R, Johnson T, Bentham P,
Phillips P (2012) Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med 366, 893–903.
2. Xu H, Garcia-Ptacek S, Jönsson L, Wimo A, Nordström P, Eriksdotter M (2021) Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality. Neurology 96, e2220–e2230.
CONFLICT OF INTEREST: None Reported
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