Charting New Territories in Early Alzheimer’s Disease: Insights Into A Treating Physician’s Experience with LEQEMBI® (lecanemab-irmb)


Wendell Helveston, M.D.

Wendell Helveston, M.D.

Though an estimated five to seven million older Americans may have mild cognitive impairment (or MCI) due to Alzheimer’s disease (or AD), AD often remains underdiagnosed.1 AD is a progressive and relentless disease caused by a continuous underlying process.1,2 Over recent years, the field has witnessed a surge of advancements in AD research, reshaping the landscape of diagnostics and treatment.3 This progress holds promise for deepening our understanding of this complex condition. While there are no neurocognitive tools that can definitively diagnose AD, there are tests that are sensitive to MCI due to AD and/or mild AD dementia and can aid in early detection. Innovations, such as the availability of positron emission tomography (PET) technology, have the potential to impact healthcare professionals’ experiences as they are evaluating patients for AD and seeking to diagnose and intervene earlier, maximizing the opportunity for benefit.1,4

Wendell Helveston, M.D., a neurologist with Hattiesburg Clinic Neurology in Hattiesburg, Mississippi, discusses the importance of an early and accurate diagnosis, his experience treating with LEQEMBI and the impact that having LEQEMBI available to patients may have on the field. LEQEMBI is indicated for the treatment of AD. Treatment with LEQEMBI should be initiated in patients with MCI or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.5 Please see Important Safety Information below and accompanying full Prescribing Information, including BOXED WARNING for Amyloid Related Imaging Abnormalities (ARIA). Dr. Helveston's observations underscore the clinical data and the potential for treatment options to make an impact on the lives of people living with early AD and their families by offering a newfound sense of hope.

How has the Alzheimer’s disease landscape evolved, and what major advancements have you seen for early diagnosis of the disease?

Dr. Helveston: AD is a progressive and relentless condition,1 robbing people of their future and their pasts. In my experience, there is often a misperception that nothing can be done for patients in early stages of disease.4 However, because of significant advancements in the field of AD, from diagnostics to treatment, this may no longer be the case.3 We do know that a prompt diagnosis of AD and early intervention are important, because intervening early may delay disease progression.1

There is an urgency to diagnose early, but this has historically been challenging, as patients are often resistant to having a lumbar puncture, which is one of two widely used and well-validated modalities to assess AD pathophysiology in vivo.1,4 With the increasing availability of amyloid imaging using positron emission tomography (PET), the second of the well-established modalities,4,6 approximately 95% of patients in our clinic are choosing to do the test. Confirmation of amyloid beta improves our diagnosis and work-up process.

Screening patients as early as possible can lead to an exact diagnosis, which is important to them and their families because it removes uncertainties. When you take the uncertainty about a diagnosis away, it helps patients and their families because they can educate themselves and grow to understand where things are headed with the disease. Early diagnosis with blood-based biomarkers has recently shown promise to simplify the diagnostic and prognostic work-up of AD. This gives patients the chance to benefit from opportunities to improve quality of care, build a plan for the future, and access treatments that may delay progression and slow cognitive and functional decline.1,4,6

Can you share more about available treatment options?

Dr. Helveston: When it comes to treatment options, we have only had symptomatic treatments available until recently.1 Ever since the amyloid cascade hypothesis became a leading theory of AD pathogenesis, targeting amyloid beta has been the main direction of developing AD treatment over the past decades.7 Various anti-amyloid theories were rigorously investigated, marking significant strides in our understanding of the disease's progression.7

Research in AD has evolved to focus on diagnosing and treating patients earlier, and the Phase 3 Clarity AD study of LEQEMBI included patients at the earliest stage of the disease.4-5 Today, LEQEMBI is the first anti-amyloid AD treatment shown to slow disease progression in a clinically meaningful way in early AD patients.8 LEQEMBI works to clear more than just amyloid plaque. It is dual-acting, meaning it supports neuronal function by clearing the highly toxic protofibrils that can continue to cause neuronal injury and death even after plaques are cleared.2,5,11-15 Lecanemab-irmb is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble forms (oligomers and protofibrils) and insoluble forms (fibrils) of amyloid beta.5

At my clinic, we’re excited. This treatment has the potential to take us from a diagnose and watch specialty to a treatment specialty in neurology. We might not have a cure for AD yet, but slowing progression and addressing a key underlying aspect of the disease is an important step in treating AD.

Antibodies targeting amyloid plaques, including LEQEMBI, can cause amyloid-related imaging abnormalities, often referred to as ARIA.5 ARIA is most commonly seen as temporary swelling in areas of the brain that usually resolves over time and can be managed during treatment with dosing interruptions.5 Most people with this type of swelling in the brain do not experience symptoms—however, some people may have symptoms, such as headache, confusion, dizziness, vision changes, nausea, difficulty walking, and seizures.5 It’s also important to note LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI.5 Reactions have included angioedema and anaphylaxis.5 Testing and discussion for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA.5 Prescribers should inform patients that this is a physician-patient decision. Please see Important Safety Information below and accompanying full Prescribing Information, including Boxed WARNING.

What can you share about your experience with prescribing LEQEMBI thus far?

Dr. Helveston: In my experience, treatment with LEQEMBI has been consistent with the clinical trial data we’ve seen. In the Phase 3 Clarity AD trial, LEQEMBI was shown to slow cognitive and functional decline over 18 months with continued treatment, as measured by the Clinical Dementia Rating Sum of Boxes (or CDR-SB), a cognitive and functional scale (-0.45 [-27%], p<0.0001).5 Clarity AD was an 18-month, global, placebo-controlled, double-blind, parallel-group, randomized clinical trial of 1795 patients with MCI due to AD (n=528/859) or mild AD dementia (n=331/859) with confirmed amyloid beta pathology. Patients were randomized 1:1 to receive LEQEMBI 10 mg/kg (IV infusion) or placebo (IV infusion) once every 2 weeks.5

While on treatment with LEQEMBI, my patients have been able to stay on track with their appointments every two weeks, and that’s important because even though they cannot feel LEQEMBI working day to day, each infusion helps keep LEQEMBI working in their body and treat the disease. This allows patients to have the opportunity to keep playing the roles they have been.

What advice would you share with neurologists and specialists treating AD and navigating these evolving discussions with their patients?

Dr. Helveston: I would say that they must understand that in the current landscape of AD treatment, the option of doing nothing is not viable. We cannot delay intervention – if we do, we risk patients becoming ineligible for certain treatments as the disease progresses. While decisions surrounding interventions are often difficult, the ramifications of not acting are more severe. There is no cure, but this is progress. The first plane ever built only made it 150 feet. Now, we can travel the world in a jet. Continued research and innovation are essential to improving outcomes for our patients.

Learn more about LEQEMBI at



LEQEMBI is indicated for the treatment of Alzheimer’s disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment 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 amyloid related imaging abnormalities (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 usually asymptomatic, although serious and life-threatening events rarely can occur. Serious intracerebral hemorrhages >1 cm, some of which have been fatal, have been observed in patients treated with this class of medications.
    - Apolipoprotein E ε4 (ApoE ε4) Homozygotes: Patients who are ApoE ε4 homozygotes (approximately 15% of Alzheimer’s disease patients) treated with this class of medications, including LEQEMBI, 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. Prior to testing, 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 Alzheimer’s disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with LEQEMBI.


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.



  • LEQEMBI can cause ARIA-E and ARIA-H. ARIA-E can be observed on MRI as brain edema or sulcal effusions, and ARIA-H as microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with Alzheimer’s disease. ARIA-H associated with monoclonal antibodies directed against aggregated forms of beta amyloid generally occurs in association with an occurrence of ARIA-E. ARIA-H and ARIA-E can occur together.
  • ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. Reported symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time.

ARIA Monitoring and Dose Management Guidelines

  • Obtain recent baseline brain magnetic resonance imaging (MRI) prior to initiating treatment with LEQEMBI. Obtain an MRI prior to the 5th, 7th and 14th infusions.
  • Recommendations for dosing in patients with ARIA-E and ARIA-H depend on clinical symptoms and radiographic severity. Depending on ARIA severity, use clinical judgment in considering whether to continue dosing, temporarily discontinue treatment, or permanently discontinue LEQEMBI.
  • Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. If a patient experiences symptoms suggestive of ARIA, 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.
  • There is no experience in patients who continued dosing through symptomatic ARIA-E or through asymptomatic, but radiographically severe, ARIA-E. There is limited experience in patients who continued dosing through asymptomatic but radiographically mild to moderate ARIA-E. There are limited data in dosing patients who experienced recurrent ARIA-E.

Incidence of ARIA

  • In Study 2, symptomatic ARIA occurred in 3% (29/898) of LEQEMBI-treated patients. Serious symptoms associated with ARIA were reported in 0.7% (6/898) of patients treated with LEQEMBI. Clinical symptoms associated with ARIA resolved in 79% (23/29) of patients during the period of observation.
  • Including asymptomatic radiographic events, ARIA was observed in LEQEMBI: 21% (191/898); placebo: 9% (84/897). ARIA-E was observed in LEQEMBI: 13% (113/898); placebo: 2% (15/897). ARIA-H was observed in LEQEMBI: 17% (152/898); placebo: 9% (80/897). There was no increase in isolated ARIA-H for LEQEMBI vs placebo.

ApoE ε4 Carrier Status and Risk of ARIA

  • In Study 2, 16% (141/898) of patients in the LEQEMBI arm were ApoE ε4 homozygotes, 53% (479/898) were heterozygotes, and 31% (278/898) were noncarriers.
  • 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%). Among patients treated with LEQEMBI, symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes compared with 2% of heterozygotes and 1% of noncarriers. Serious events of ARIA occurred in 3% of ApoE ε4 homozygotes, and approximately 1% of heterozygotes and noncarriers.
  • The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.

Radiographic Findings

  • The majority of ARIA-E radiographic events occurred early in treatment (within the first 7 doses), although ARIA can occur at any time and patients can have more than 1 episode. The maximum radiographic severity of ARIA-E in patients treated with LEQEMBI was mild in 4% (37/898), moderate in 7% (66/898), and severe in 1% (9/898). Resolution on MRI occurred in 52% of ARIA-E patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection. The maximum radiographic severity of ARIA-H microhemorrhage in LEQEMBI-treated patients 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). Among LEQEMBI-treated patients, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes 5% (7/141), compared to heterozygotes 0.4% (2/479) or noncarriers 0% (0/278). Among LEQEMBI-treated patients, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes 13.5% (19/141), compared to heterozygotes 2.1% (10/479) or noncarriers 1.1% (3/278).

Intracerebral Hemorrhage

  • Intracerebral hemorrhage >1 cm in diameter was reported in 0.7% (6/898) of patients in Study 2 after treatment with LEQEMBI compared to 0.1% (1/897) on placebo. Fatal events of intracerebral hemorrhage in patients taking LEQEMBI have been reported.

Concomitant Antithrombotic Medication:

  • In Study 2, 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 patients) in patients taking LEQEMBI with a concomitant antithrombotic medication at the time of the event compared to 0.6% (3/545 patients) 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 patients) compared to none in patients who received placebo.
  • Because intracerebral hemorrhages >1 cm in diameter have been observed in patients taking LEQEMBI, additional 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.

Other Risk Factors for Intracerebral Hemorrhage:

  • Patients were excluded from enrollment in Study 2 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) that could potentially increase the risk of intracerebral hemorrhage. The presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy, which has an increased risk for intracerebral hemorrhage. Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for intracerebral hemorrhage and in particular for patients who need to be on anticoagulant therapy.


Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred in LEQEMBI-treated patients. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction, and initiate appropriate therapy.


  • In Study 2, infusion-related reactions were observed in LEQEMBI: 26% (237/898); placebo: 7% (66/897), and the majority of cases in LEQEMBI-treated patients (75%, 178/237) occurred with the first infusion. Infusion-related reactions were mostly mild (69%) or moderate (28%) in severity. Infusion-related reactions resulted in discontinuations in 1% (12/898) of LEQEMBI-treated patients. Symptoms of infusion-related reactions 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 infusion-related reaction, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Prophylactic treatment with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids prior to future infusions may be considered.


  • In Study 2, the most common adverse reaction leading to discontinuation of LEQEMBI was ARIA-H microhemorrhages that led to discontinuation in 2% (15/898) of patients treated with LEQEMBI compared to <1% (1/897) of patients on placebo.
  • In Study 2, the most common adverse reactions reported in ≥5% of patients treated with LEQEMBI (N=898) and ≥2% higher than placebo (N=897) were infusion-related reactions (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%).

Please see full Prescribing Information for LEQEMBI, including Boxed WARNING.


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