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Today, the FDA granted traditional approved to lecanemab (branded as Leqembi), a monoclonal antibody from Eisai and Biogen for adult patients with Alzheimer’s disease. The agency made the decision on the basis of a confirmatory trial that showed its clinical benefit.
The drug, which reduces the formation of amyloid plaques in the brain, is the first of its kind to transition from an accelerated approval to a traditional approval for Alzheimer’s treatment.
Leqembi’s annual launch price is $26,500.
Following approval, lecanemab stands to potentially gain Medicare coverage with qualifications.
The approval of Leqembi is a positive step forward and will spur further advances and investments in Alzheimer’s research, according to Dr. Howard Fillit, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF).
“We finally have clarity around amyloid’s modest effect on cognitive decline.” Dr. Fillit said in a press release. “Now, it is more important than ever to double down and widen our focus to developing the next generation of drugs based on the biology of aging that can lead to a combination therapy and precision medicine approach.”
ADDF got a $200 million gift earlier this year to help advance new therapies for Alzheimer’s.
In a recent survey from Sermo, 81% of more than 650 physicians supported lecanemab’s full approval. Nine out of ten felt it gives hope to patients, and 82% were optimistic about an Alzheimer’s cure.
Lecanemab: Promising drug with significant side effects
Lecanemab underwent a confirmatory trial to show its clinical benefit. The confirmation came from Study 301 (CLARITY AD), a phase 3 randomized, controlled clinical trial of 1,795 Alzheimer’s disease patients. It showed lecanemab significantly reduces cognitive decline over 18 months.
While promising, the drug has side effects including headaches, infusion-related reactions and amyloid-related imaging abnormalities (ARIA) — temporary swelling or small bleeds in the brain that may lack symptoms. Intracerebral hemorrhages can occur and be fatal. Patients with the ApoE ε4 allele have higher ARIA risk, so FDA recommends testing before starting lecanemab therapy.
Lecanemab’s indiction is limited to mild cognitive impairment or mild Alzheimer’s dementia.
The drug’s use is contraindicated in patients with serious hypersensitivity to lecanemab or its inactive ingredients. The FDA included a boxed warning about ARIA risks.
Here is a table summarizing some key experimental Alzheimer’s drugs, their development status, trial details and results:
| Drug Name | Mechanism of Action | Trial Phase | Trial Name | Number of Participants | Duration | Result |
|---|---|---|---|---|---|---|
| Aducanumab (Aduhelm) | Anti-amyloid beta antibody | Approved | ENGAGE, EMERGE | 3,285 | 78 weeks | Reduced brain amyloid plaque and slow cognitive and functional decline |
| Lecanemab (BAN2401) | Anti-amyloid beta antibody | Phase 3 | Clarity AD (NCT03887455), AHEAD 3-45 (NCT04468659) | Clarity AD: 1,795; AHEAD 3-45: 1,400 (planned) | Clarity AD: 78 weeks; AHEAD 3-45: 216 weeks | Moderate reduction in cognitive decline |
| Donanemab | Anti-amyloid beta antibody | Phase 2 | TRAILBLAZER-ALZ | 257 | 76 weeks | Reduced the amyloid plaque level and the global tau load; slowed cognitive decline |
| Gantenerumab | Anti-amyloid beta antibody | Phase 3 | GRADUATE I (NCT03444870), GRADUATE II (NCT03443973) | 1,965 | 116 weeks | Did not meet primary endpoint; slowed clinical decline but was not statistically significant. Had previously won Breakthrough Therapy designation from FDA. |
| Azeliragon (TTP488) | Inhibitor of the Receptor for Advanced Glycation Endproducts (RAGE) | Phase 3 | STEADFAST | 800 | 18 months | Trial terminated owing to lack of efficacy at the 5 mg/kg dose |
| Suvorexant (Belsomra) | Dual orexin receptor antagonist | Approved for insomnia | NCT02750306 | 285 | 4 weeks | Improved total sleep time and wake after sleep onset measures |
| Sodium oligomannate (GV-971) | Reconstitutes gut microbiota, reduces neuroinflammation | Phase 3 | NCT02293915 | 818 | 36 weeks | Improved cognition (unadjusted difference in ADAS-Cog-12 score between the experimental treatment and placebo groups was −2.54 points) |