Optum to payers: Two new Alzheimer's drugs are in the pipeline
According to Optum, there's a high unmet need for treatments for Alzheimer's disease, as current treatments have lacked efficacy.
Photo: Jeff Lagasse/Healthcare Finance News
A new Optum report highlighting upcoming medications in the drug pipeline is meant as a heads-up for payers as they track developments with a couple of therapies for Alzheimer's disease – lecanemab and donanemab.
Lecanemab, from Eisai/Biogen, is under review for the treatment of mild cognitive impairment (MCI) due to Alzheimer's disease. It's an antibody that binds to fibrillar amyloid, a soluble, toxic version of beta-amyloid, and by binding, lecanemab can neutralize the fibrillar amyloid and help "tag" it, so the immune system can clear it from the brain.
As part of the Aduhelm accelerated approval process, the FDA approved the drug by using reduction in beta-amyloid plaque as a surrogate endpoint that was "reasonably likely" to predict a clinical benefit to patients with early Alzheimer's disease.
Phase 2 trial data has been characterized as showing "robust plaque clearance" plus a "modest slowing" in cognitive decline.
Since that time, new Phase 3 trial results were published in the New England Journal of Medicine in November, which studied the effects of lecanemab in patients with early Alzheimer's. Patients were randomized to receive lecanemab or a placebo once every two weeks. At 18 months, patients taking lecanemab showed a 27% slower cognitive and functional decline compared with those taking a placebo in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. This corresponded with a -0.45-point difference versus placebo on the 18-point CDR-SB scale.
Like lecanemab – and Aduhelm – donanemab is a type of beta-amyloid targeted antibody. It works slightly differently than lecanemab in that it's designed to bind to beta-amyloid proteins that have already aggregated into plaques. It works by stimulating the immune system to attack beta-amyloid plaques and clear them from the brain
The FDA submission for accelerated approval for donanemab was based on TRAILBLAZER-ALZ, a Phase 2, randomized, double-blind, placebo-controlled study in 257 patients with early symptomatic Alzheimer's disease. Donanemab met its primary study objective, slowing the clinical decline of Alzheimer's disease by 32% relative to placebo on the Integrated Alzheimer's Disease Rating Scale (iADRS) at 76 weeks.
Also, there was a "substantial reduction" of amyloid plaque, with 68% of patients who received donanemab achieving complete amyloid clearance
That study also compared donanemab to Adulhelm. Almost 150 patients with early symptomatic Alzheimer's disease received one of the two drugs. At six months, patients receiving donanemab had cleared amyloid from the brain in approximately 38% of those treated, compared to approximately 2% for those given Aduhelm.
WHAT'S THE IMPACT
According to Optum, there's a high unmet need for treatments for Alzheimer's disease, since it's a leading cause of illness and death among the elderly. Existing treatment options have been ineffective.
In June 2021, the FDA approved Aduhelm (aducanumab), the first amyloid beta-directed antibody, via the accelerated approval pathway based on reductions in amyloid beta plaques. Subsequently, a Centers for Medicare and Medicaid Services National Coverage Determination limited Medicare coverage for Aduhelm and other beta-amyloid targeted therapies to patients enrolled in clinical trials because of unknown clinical benefit.
Lecanemab would be the second drug in the class with FDA approval through the accelerated approval pathway that was followed to approve Aduhelm, based on the surrogate of reductions in beta-amyloid plaques.
Like lecanemab, donanemab would be another beta-amyloid targeted therapy.
THE LARGER TREND
A December 2022 staff report by two House committees pointed to alleged irregularities in the Food and Drug Administration's approval of the Alzheimer's drug Aduhelm.
In January, CMS released a proposed National Coverage Determination decision memorandum that said the NCD would cover FDA-approved monoclonal antibodies that target amyloid for the treatment of Alzheimer's disease through coverage with evidence development, meaning for Medicare recipients enrolled in qualifying clinical trials.
Twitter: @JELagasse
Email the writer: Jeff.Lagasse@himssmedia.com
