ANA Past President David Holtzman with Alzheimer’s Disease Update: CMS Limits Coverage of Aduhelm
Earlier this month, the Centers for Medicare & Medicaid Services (CMS) announced a decision to limit coverage of Biogen's Alzheimer's drug Aduhelm™ (aducanumab) to patients enrolled in clinical trials.
With a listed price tag of $28,200 a year, the monoclonal antibody was directed against amyloid beta and showed effectiveness during clinical trials in dissolving plaques in the brain. However, its clinical impact on the functioning of patients in earlier stages of Alzheimer’s disease was not clear such that in November 2020 an expert panel voted overwhelmingly to advise the FDA to reject it. (The intravenous drug also produced brain swelling or microhemorrhages in 41 percent of patients who received the high dose of the drug, although Biogen’s research showed that these side effects resolved with no apparent harm in most cases.)
Nevertheless, the FDA did approve Adulhem, and the CMS decision not to cover the therapy has angered some patient advocates and members of the drug industry. In addition, many of the nation’s most prestigious hospitals — including the Cleveland Clinic, Johns Hopkins Hospital, Barnes-Jewish, and Massachusetts General — have declined to offer it to patients.
“CMS’ final decision is very similar to what we and lots of people suggested,” said ANA Past President David M. Holtzman, MD, FANA, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology and Scientific Director of the Hope Center for Neurological Disorders at Washington University School of Medicine. His hospital didn’t make Aduhelm available in its formulary, so he and other neurologists at his institution have not prescribed it, although he has referred Alzheimer’s patients for clinical trials that are ongoing of different monoclonal antibodies targeting amyloid.
“The clinical evidence isn’t yet convincing that Aduhelm showed a clinical benefit, so I think deciding that for it to be paid for that would have to be in a randomized clinical trial makes sense,” Holtzman said. “With regard to the other agents in phase III trials, three are close to completion. If the FDA approves any of those based on clinical evidence, it would seem they should pay for those agents.”
On July 14, 2021, the ANA Executive Committee issued a statement urging the FDA to ensure that Biogen complete a phase IV confirmatory study as soon as possible to confirm whether clinical efficacy is observed.
If phase II studies bear out for both Eli Lilly’s donanemab and Eisai’s lecanemab — both treatments showed clinical benefit in smaller studies — Holtzman thinks it’s possible that one of those agents, or Hoffmann-LaRoche’s gantenerumab, could be approved by the end of 2023.
If that happens, “I think it will be the beginning of a whole new era,” Holtzman said. The antibodies would be given during the first clinical stage of Alzheimer’s disease to slow its progression, Holtzman said, noting that the compounds don’t reverse cognitive impairment. As is the case in cancer treatment, it’s likely that for mild dementia, a combination of drugs on top of monoclonal antibodies will have greater benefit.
For now, Holtzman says he’ll watch what happens with the other anti-amyloid antibodies over the next year. “We’ll see what the [clinical trial] results show and hopefully discover how we can do better for our patients.”