Lecanemab, also called BAN2401, is a potential immunotherapy for Alzheimer’s disease that is being jointly developed by the U.S.-based biotechnology company Biogen and the Japanese healthcare company Eisai.
The experimental treatment consists of a monoclonal antibody against a form of beta-amyloid protein that accumulates in the brain of people with Alzheimer’s disease, causing the hallmark cognitive impairment and functional disability. The antibody binds to amyloid, which could reduce the protein’s presence in the brain and potentially slow the progress of the disease.
In September 2021, Eisai started work on a rolling submission to the U.S. Food and Drug Administration (FDA) for a Biologics License Application (BLA) for lecanemab for early Alzheimer’s. Under the normal process, the entire BLA application would be submitted as one package to federal regulators. Here, as a rolling submission, Eisai will turn in each portion of its application as it’s completed.
Once the BLA is accepted by the regulatory agency, a Prescription Drug User Fee Act (PDUFA) date can be set. That date, known as the FDA action date, is expected to mark the end of the agency’s review.
The submission is being done under the accelerated approval pathway. Lecanemab was granted Breakthrough Therapy status by the FDA in June 2021, a designation that expedites the development and review of medicines for serious or life-threatening conditions.
Meanwhile, lecanemab has been added to the Tau Next Generation (Tau NexGen) clinical trial, which is now evaluating the anti-amyloid antibody in addition to an anti-tau antibody as a potential treatment for early Alzheimer’s. The team of scientists leading the Tau NexGen trial — known as the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) — chose the therapy in agreement with the FDA and the European Medicines Agency.
How BAN2401 works
Alzheimer’s symptoms result from both brain cell death and a loss of connections between these cells. It is not fully understood what causes this cell death, but the disease is characterized by the accumulation of certain proteins in the brain. One of these proteins is beta-amyloid, which can form clumps called plaques that disrupt the communication between brain cells and may trigger inflammation, which leads to cell death.
BAN2401 is an antibody designed to bind to a soluble, toxic version of beta-amyloid. It is hoped that this binding can neutralize beta-amyloid and help “tag” it, so the immune system can clear it from the brain before it clumps and forms plaques.
BAN2401 in clinical trials
BAN2401 has been tested in two Phase 1 clinical trials (NCT01230853 and NCT02094729) to assess its safety, tolerability, and pharmacokinetics (how the body absorbs, circulates, and processes a medication). Results published for one of these trials (NCT01230853) showed that BAN2401 was reasonably safe and well-tolerated at various doses.
A large, ongoing Phase 2 clinical trial (NCT01767311), called Study 201, examined the effectiveness of various intravenous doses of BAN2401 as well as their safety and tolerability. The initial study took place over 18 months, followed by a now-underway extension phase. Results of the initial 18-month study in 856 patients were positive at the highest twice-monthly (10 mg/kg) dose, showing a statistically significant 30% decrease in cognitive decline as well as a lower accumulation of beta-amyloid in the brain compared to those given a placebo. Cognitive decline was measured by an assessment tool called ADCOMS, and the amount of beta-amyloid in the brain was assessed using positron emission tomography (PET) specific for amyloid. More detailed results were announced in July 2018. The study is now in its extension phase.
A new Phase 3 clinical trial (NCT03887455), called Clarity AD, is now testing the safety and efficacy of BAN2401 (10 mg/kg drug every two weeks) against placebo in people with mild Alzheimer’s disease, Eisai announced in Match 2019. The 18-month study, to be followed by a long-term and open-label extension phase, aims to recruit 1,566 patients, who will be split evenly into treatment and control groups. Its primary endpoint, or goal, is changes from baseline in the Clinical Dementia Rating–Sum of Boxes (CDR-SB). Secondary endpoints include changes in other cognitive tests, such as ADCOMS and the AD Assessment Scale-Cognitive Subscale (ADAS-cog), and beta-amyloid levels measured by PET. The study is expected to finish in March 2024.
Clarity AD will enroll patients with mild cognitive impairment due to Alzheimer’s disease at sites across the U.S., Europe, Canada, Japan and Korea.
Last updated: December 6, 2021
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