A new disease-modifying Alzheimer's drug, lecanemab — which will be distributed under the brand name Leqembi — today secured fast-tracked FDA approval.
Update: As of July 6, 2023, the drug has full, traditional FDA approval.
Today, the Food and Drug Administration approved Leqembi (generic name lecanemab), a new Alzheimer’s drug by drugmakers Eisai and Biogen. It is the second-ever monoclonal antibody therapy to receive FDA approval for Alzheimer’s disease. The first was Aduhelm, in summer of 2021. The FDA granted this application Fast Track, Priority Review and Breakthrough Therapy designations.
Monoclonal antibodies like lecanemab are designed to target the disease itself by targeting beta-amyloid protein plaques that build up in the brain during Alzheimer’s.
While it has been in the research phase for decades, this “anti-amyloid” approach is a disruptor when it comes to therapies on the market; all other available Alzheimer’s drugs are designed to treat the symptoms of Alzheimer’s, like brain fog, confusion and memory problems.
Data from the drug’s Phase 3 clinical trials shows Leqembi (lecanemab) was successful in helping to clear these toxic plaques from the brain, improving cognition by a small amount.
Does Leqembi (lecanemab) work?
Leqembi is designed to clear amyloid plaque from the brain — an approach the drugmakers believe can actually stop or prevent the cognitive decline caused by Alzheimer’s disease. Scientists still don’t know definitively whether this amyloid protein plaque is the cause of Alzheimer’s, or just a symptom. But, in trials, Leqembi’s (lecanemab)’s approach did appear to improve cognitive function in patients by just under half a point (0.45 points) on an 18-point scale. (Some clinician experts have said this may not be enough of an improvement for family members to notice a difference.)
How is Leqembi different from Aduhelm, the last disease-modifying drug to be approved by the FDA?
In principal, the drugs are similar and aim to dissolve or prevent beta-amyloid plaque from forming inside the brain. Lecanemab is targeting an earlier stage of the protein that contributes to the formation of these plaques.
Does Leqembi (lecanemab) have side effects?
Like its predecessor — monoclonal antibody drug Aduhelm (generic name aducanumab) — lecanemab carries the risk of side effects including ARIA — brain swelling or brain brain bleeds. ARIA is often asymptomatic. In rare cases it can be severe.
In the aducanumab trials leading up to Aduhelm’s FDA approval for Alzheimer’s treatment in the summer of 2021, ARIA occurred in more than one third of patients receiving the high dose of the drug. Comparatively, lecanemab appears safer: One in five people who received lecanemab experienced ARIA. Among these cases — only 3.5 percent were symptomatic.
Certain factors may increase a person’s likelihood of an adverse event while taking a monoclonal antibody drug for Alzheimer’s. These include, according to the drugmaker, carrying two copies of ApoE4, or the “Alzheimer’s Gene;” cerebral amyloid angiopathy; and blood thinners (anticoagulants).
Up to 80 percent of people with Alzheimer’s have a condition called cerebral amyloid angiopathy (CAA). In CAA, amyloid plaques crowd the brain’s blood vessels, replacing the muscles that normally surround them. Lecanemab and other anti-amyloid antibodies weaken the blood vessels by getting rid of these plaques. The blood vessels become weak and susceptible to hemorrhage. People living with Alzheimer’s and CAA might have a higher risk of brain bleeds if they opt for a monoclonal antibody treatment like lecanemab.
According to third-party experts who reviewed cases of lecanemab deaths during the open-label trial extension in 2022, anticoagulant use may have contributed to worsening of ARIA in the first two of three reported deaths from the open label-extension trial.
Where can you get Leqembi?
Lecanemab is administered by an intravenous infusion. Now that the drug has FDA approval, doctors will be able to prescribe lecanemab. However, monoclonal antibody drugs, this one included, have only been tested among people with mild cognitive impairment or patients in a very early stage of Alzheimer’s. It is still unknown what the impact may be for people in the later stages of Alzheimer’s disease.
These therapies are also quite complicated to produce, and they must be administered by a specialist, which makes them more expensive and not as accessible to people who live far from major metropolitan areas or research universities.
How much will Leqembi cost?
The cost will be approximately $26,500 per year.
Will it be covered by insurance?
The question of insurance coverage is also up in the air: Despite Aduhelm’s approval from the FDA, the Center for Medicare and Medicaid Services (CMS) declined to pay for Aduhelm after a series of hiccups and launched its own study to seek out better data. The big question remains whether the CMS will approve reimbursements for other Alzheimer’s -mab drugs, this one included.
Is Leqembi safe?
At this point, there is not yet enough data to determine whether any of the above factors increase the risk of developing complications during the course of Leqembi (lecanemab) treatment. Instead, it will be up to patients and their clinicians to be vigilant for signs of side effects and stay one step ahead.
“Assessment of an individual patient’s risk versus benefit profile is a crucial part of clinical decision making and I hope that the prescribing label for the drug, if approved, will provide detailed guidance on this issue,” Madhav Thambisetty, neurologist and senior clinical investigator at the National Institute of Aging, told Being Patient.
According to Eric Smith, a neurologist at the University of Calgary, patients who receive the drug will need to be monitored through several annual MRI scans and education may be needed to ensure that doctors outside of specialized clinics recognize the signs of ARIA.
Lecanemab’s trial protocol outlined that safety MRIs should be conducted at nine and 13 weeks of treatment, then every three months for the first six months, and every six months afterward. Lon Schneider, physician and professor of psychiatry at Keck School of Medicine tweeted that a Risk Evaluation and Mitigation Strategy (REMS) may need to be implemented.
This means that the FDA could also require Eisai and Biogen to develop strategies, like increased monitoring or physician education, to ensure the safety of the patients taking Leqembi (lecanemab).