Leqembi approval offers renewed hope for novel Alzheimer's disease treatments

US officials have granted full approval to Leqembi, the first medication to demonstrate modest effectiveness in slowing cognitive decline associated with Alzheimer’s disease.

Developed by Japanese drug-maker Eisai and comarketed with Biogen Inc (NASDAQ:BIIB), the American pharmaceutical giant, the FDA's endorsement paves the way for Medicare and other insurance plans to cover the treatment for individuals with mild dementia and early symptoms of Alzheimer's disease.

That’s good news for Alzheimer’s patients because Leqembi doesn’t come cheap. Eligible patients will be responsible for paying the standard 20% coinsurance, which amounts to approximately $5,300 based on Leqembi's annual cost of $26,500.

Thankfully, the Centers for Medicare and Medicaid Services (CMS) announced that Leqembi will be covered broadly through a CMS-facilitated registry, which will gather data on the treatment's effectiveness. To qualify for Medicare coverage, patients must be enrolled in Medicare, diagnosed with mild cognitive impairment or mild Alzheimer's disease dementia, show evidence of beta-amyloid plaque in the brain, and have a physician participating in a qualifying registry with an appropriate clinical team and follow-up care.

The approval was widely anticipated following a positive recommendation from the Advisory Committee (AdCom) and unanimous support for the confirmed clinical benefit of Leqembi. The drug slowed disease progression by 27% over 18 months in those with mild cognitive impairment or early-stage Alzheimer's.

But Leqembi has been linked to brain swelling, hemorrhages, and even three deaths during trials. The label for Leqembi will include a black-box warning, highlighting the risk of symptomatic, serious or severe ARIA (amyloid-related imaging abnormalities) in patients who are homozygotes for the ApoE4 gene. The label also cautions against the concurrent use of anticoagulants and notes the association of cerebral amyloid angiopathy (CAA) with an increased risk of intracerebral hemorrhage.

Important breakthrough

For Alzheimer’s patients, the approval represents a significant milestone as prior medications only addressed disease symptoms. Unlike its predecessors, Leqembi targets the brain's beta-amyloid protein, a potential Alzheimer's culprit.

Patients with mild cognitive impairment or early-stage Alzheimer's are eligible for Leqembi, administered intravenously biweekly.

For analysts, the approval is an important milestone in de-risking the launch of Leqembi.

“Given approval/reimbursement was entirely consensus expectation, we do not expect a significant stock reaction though would highlight this is an important de-risking event for the Leqembi launch,” analysts at UBS wrote recently.

“Focus now will likely shift to the launch and cost-cutting and business development.”

New frontiers for Alzheimer’s treatment

Leqembi’s approval is shining a spotlight on other treatment avenues for Alzheimer’s, a devastating disease that has confounded the medical community.

Here’s a look at other pharmaceutical companies working on their own drug discovery programs:

• Eli Lilly and Co (NYSE:LLY) is advancing donanemab, another monoclonal antibody that has shown promising results in a Phase 3 TRAILBLAZER-ALZ 2 study, significantly slowing cognitive and functional decline in individuals with early symptomatic Alzheimer's disease. The study's primary endpoint, which measured change from baseline until 18 months on the integrated Alzheimer's Disease Rating Scale (iADRS), was successfully met.
• Saracatinib is another candidate being developed by AstraZeneca PLC (LSE:AZN). Trials in mice initially turned off a protein that allowed synapses to start working again. The animals in the study experienced a reversal of some memory loss. Human trials for saracatinib as a possible Alzheimer's treatment are now underway.
• Leukine is currently being investigated by Partner Therapeutics as a potential treatment for cognitive problems related to Alzheimer’s disease. Originally developed by Sanofi SA (ADR) (NYSE:SNY), the immune system stimulator works to boost the number and function of white blood cells and so reduce the risk of infection.
• BioVie Inc (NASDAQ:BIVI) is studying its novel molecule, NE3107, in people diagnosed with Alzheimer’s Disease. According to BioVie’s hypothesis, selective modulation of inflammation, and the enhancement of energy transfer (insulin sensitivity) in the brain, may be able to improve memory and thinking, and may protect against neurodegeneration. NE3107 is the only anti-inflammatory agent currently in Phase 3 development for Alzheimer’s.
• Tiziana Life Sciences Ltd (NASDAQ:TLSA) is planning to file an Investigational New Drug Application for Intranasal Foralumab as a treatment for Alzheimer's. There are no FDA-approved treatments for Alzheimer’s disease specific to neuroinflammation, and Tiziana is planning to study three months' administration of intranasal foralumab in Alzheimer’s disease patients to see if neuroinflammatory activated microglia will return to the baseline homeostatic state.

Contact Angela at angela@proactiveinvestors.com

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