Leqembi Injection, an Easier Alzheimer’s Treatment, Awaits FDA Approval
LEQEMBI® is the newest Alzheimer's drug. It is administered in hospitals via IV. Biogen applied to the FDA for approval of a home version using an "Autoinjector". See how it works and learn its advantages.
Eisai has initiated the rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for generic lecanemab-irmb (U.S. brand name: LEQEMBI®) subcutaneous autoinjector for weekly maintenance dosing. LEQEMBI® was granted Fast Track designation by the FDA. LEQEMBI is indicated for the treatment of Alzheimer’s disease (AD)in patients with Mild Cognitive Impairment (MCI)or mild dementia stage of disease (collectively referred to as early AD).
The BLA is based on data from the Clarity AD (Study 301) open-label extension (OLE) and modeling of observed data.
Using Leqembi® at Home
If approved by the FDA, the LEQEMBI autoinjector could be used to administer LEQEMBI at home or at medical facilities. The injection process requires less time than the IV formulation. As part of the subcutaneous autoinjector 360 mg weekly maintenance regimen under review, patients who have completed the biweekly IV initiation phase would receive weekly doses that maintain effective drug concentrations to sustain the clearance of highly toxic protofibrils* which can continue to cause neuronal injury even after the amyloid-beta (Aβ) plaque has been cleared from the brain.
Easier, Fewer Hospital Visits, Less Nursing
Alzheimer’s is an ongoing neurotoxic process that begins before and continues after plaque deposition. Data suggest that early and continuing treatment may prolong the benefit even after plaque is cleared from the brain.
This SC autoinjector offers a number of obvious advantages:
It is easier for patients and their care partners to use,
It may reduce the need for hospital visits and nursing care compared to intravenous (IV) administration.
This could save the patient money.
In addition, it could potentially help maintain the clinical and biomarker benefits,
Subcutaneous maintenance dosing may be more convenient for patients and their care partners to continue the treatment.
Approval Process
LEQEMBI, administered via IV, is now approved in the U.S., Japan and China, and applications have been submitted for review in the European Union, Australia, Brazil, Canada, Hong Kong, Great Britain, India, Israel, Russia, Saudi Arabia, South Korea, Taiwan, Singapore and Switzerland. Eisai submitted to the FDA a Supplemental Biologics License Application (sBLA) for monthly LEQEMBI intravenous (IV) maintenance dosing in March 2024.
Eisai serves as the lead for lecanemab’s development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
* Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive, debilitating condition.1 Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction.2
More Information
Indication
LEQEMBI® [(lecanemab-irmb) 100 mg/mL injection for intravenous use] is indicated for the treatment of Alzheimer’s disease (AD). Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.
Monoclonal antibodies directed against aggregated forms of amyloid beta, including LEQEMBI, can cause ARIA, characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing of ARIA vary among treatments. ARIA usually occurs early in treatment and is asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. Serious intracerebral hemorrhages >1 cm, some fatal, have been observed with this class of medications.Apolipoprotein E ε4 (ApoE ε4) Homozygotes: Patients who are ApoE ε4 homozygotes (~15% of patients with AD) treated with this class of medications have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Prescribers should inform patients that if genotype testing is not performed, they can still be treated with LEQEMBI; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA.Consider the benefit of LEQEMBI for the treatment of AD and the potential risk of serious ARIA events when deciding to initiate treatment with LEQEMBI.
CONTRAINDICATION
LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI. Reactions have included angioedema and anaphylaxis.
WARNINGS AND PRECAUTIONS
AMYLOID-RELATEDIMAGINGABNORMALITIES
LEQEMBI can cause ARIA-E and ARIA-H, which can occur together. ARIA-E can be observed on magnetic resonance imaging (MRI) as brain edema or sulcal effusions and ARIA-H as microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD. With this class of medications, ARIA-H generally occurs in association with ARIA-E. Reported ARIA symptoms may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms usually resolve over time.
IncidenceofARIA
Symptomatic ARIA occurred in 3% (29/898) and serious ARIA symptoms in 0.7% (6/898) with LEQEMBI. Clinical ARIA symptoms resolved in 79% (23/29) of patients during the period of observation. ARIA, including asymptomatic radiographic events, was observed: LEQEMBI, 21% (191/898); placebo, 9% (84/897). ARIA-E was observed: LEQEMBI, 13% (113/898); placebo, 2% (15/897). ARIA-H was observed: LEQEMBI, 17% (152/898); placebo, 9% (80/897). No increase in isolated ARIA-H was observed for LEQEMBI vs placebo.
ApoEε4CarrierStatusandRiskofARIA
Of the patients taking LEQEMBI, 16% (141/898) were ApoE ε4 homozygotes, 53% (479/898) were heterozygotes, and 31% (278/898) were noncarriers. With LEQEMBI, the incidence of ARIA was higher in ApoE ε4 homozygotes (LEQEMBI: 45%; placebo: 22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI: 13%; placebo: 4%). Symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes vs 2% of heterozygotes and 1% of noncarriers. Serious ARIA events occurred in 3% of ApoE ε4 homozygotes and in ~1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.
RadiographicFindings
The majority of ARIA-E radiographic events occurred within the first 7 doses, although ARIA can occur at any time, and patients can have >1 episode. Maximum radiographic severity of ARIA-E with LEQEMBI was mild in 4% (37/898), moderate in 7% (66/898), and severe in 1% (9/898) of patients. Resolution of ARIA-E on MRI occurred in 52% of patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection. Maximum radiographic severity of ARIA-H microhemorrhage with LEQEMBI was mild in 9% (79/898), moderate in 2% (19/898), and severe in 3% (28/898) of patients; superficial siderosis was mild in 4% (38/898), moderate in 1% (8/898), and severe in 0.4% (4/898) of patients. With LEQEMBI, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes (5%; 7/141) vs heterozygotes (0.4%; 2/479) or noncarriers (0%; 0/278). With LEQEMBI, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes (13.5%; 19/141) vs heterozygotes (2.1%; 10/479) or noncarriers (1.1%; 3/278).
IntracerebralHemorrhage
Intracerebral hemorrhage >1 cm in diameter was reported in 0.7% (6/898) with LEQEMBI vs 0.1% (1/897) with placebo. Fatal events of intracerebral hemorrhage in patients taking LEQEMBI have been reported.
ConcomitantAntithromboticMedication:
In Clarity AD, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed if the patient was on a stable dose. The majority of exposures to antithrombotic medications were to aspirin. Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of intracerebral hemorrhage was 0.9% (3/328) in patients taking LEQEMBI with a concomitant antithrombotic medication at the time of the event vs 0.6% (3/545) in those who did not receive an antithrombotic. Patients taking LEQEMBI with an anticoagulant alone or combined with an antiplatelet medication or aspirin had an incidence of intracerebral hemorrhage of 2.5% (2/79) vs none in patients receiving placebo. Caution should be exercised when considering the administration of anticoagulants or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI.
OtherRiskFactorsforIntracerebralHemorrhage:
Patients were excluded from enrollment in Clarity AD for findings on neuroimaging that indicated an increased risk for intracerebral hemorrhage. These included findings suggestive of cerebral amyloid angiopathy (prior cerebral hemorrhage >1 cm in greatest diameter, >4 microhemorrhages, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation). The presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy. Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for intracerebral hemorrhage and in patients who need to be on anticoagulant therapy.
ARIAMonitoringandDoseManagementGuidelines
Obtain a recent baseline brain MRI prior to initiating treatment with LEQEMBI and prior to the 5th, 7th, and 14th infusions. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. Depending on ARIA-E and ARIA-H clinical symptoms and radiographic severity, use clinical judgment when considering whether to continue dosing or to temporarily or permanently discontinue LEQEMBI. If a patient experiences ARIA symptoms, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.
HYPERSENSITIVITY REACTIONS
Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred with LEQEMBI. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy.
INFUSION-RELATED REACTIONS (IRRs)
IRRs were observed—LEQEMBI: 26% (237/898); placebo: 7% (66/897)—and the majority of cases with LEQEMBI (75%, 178/237) occurred with the first infusion. IRRs were mostly mild (69%) or moderate (28%) in severity. IRRs resulted in discontinuation of LEQEMBI in 1% (12/898). Symptoms of IRRs included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
In the event of an IRR, the infusion rate may be reduced or the infusion may be discontinued and appropriate therapy initiated as clinically indicated. Consider prophylactic treatment prior to future infusions with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids.
ADVERSE REACTIONS
The most common adverse reaction leading to discontinuation of LEQEMBI was ARIA-H microhemorrhages that led to discontinuation in 2% (15/898) with LEQEMBI vs <1% (1/897) with placebo.
The most common adverse reactions reported in ≥5% with LEQEMBI (N=898) and ≥2% higher than placebo (N=897) were IRRs (LEQEMBI: 26%; placebo: 7%), ARIA-H (LEQEMBI: 14%; placebo: 8%), ARIA-E (LEQEMBI: 13%; placebo: 2%), headache (LEQEMBI: 11%; placebo: 8%), superficial siderosis of central nervous system (LEQEMBI: 6%; placebo: 3%), rash (LEQEMBI: 6%; placebo: 4%), and nausea/vomiting (LEQEMBI: 6%; placebo: 4%).
This site was inspired by my Mom’s autoimmune dementia.
It is a place where we separate out the wheat from the chafe, the important articles & videos from each week’s river of news. Google gets a new post on Alzheimer’s or dementia every 7 minutes. That can overwhelm anyone looking for help. This site filters out, focuses on and offers only the best information. it has helped hundreds of thousands of people since it debuted in 2007. Thanks to our many subscribers for your supportive feedback.
The site is dedicated to all those preserving the dignity of the community of people living with dementia.
RECIPE: “Brain foods” are neuroprotective, fighting Alzheimer’s by lowering risk and helping to resist cognitive decline. This flavorful dish combines 4 of the best “brain foods”: fish, coconut oil, curry and fenugreek. Enjoy its Indian flair.
SLEEP VIDEO: See what kind of sleep fights Alzheimer’s and lowers its risk. Watch Harvard Alzheimer’s expert Dr. Rudy Tanzi and bestselling author Dr. Deepak
This site was inspired by my Mom’s autoimmune dementia.
It is a place where we separate out the wheat from the chafe, the important articles & videos from each week’s river of news. Google gets a new post on Alzheimer’s or dementia every 7 minutes. That can overwhelm anyone looking for help. This site filters out, focuses on and offers only the best information. it has helped hundreds of thousands of people since it debuted in 2007. Thanks to our many subscribers for your supportive feedback.
The site is dedicated to all those preserving the dignity of the community of people living with dementia.