Recent Updates In Lecanemab

The most recent information about psychiatric illnesses is provided purely for informational purposes; it does not replace medical attention. Further information can be obtained by consulting the manufacturing labeling.

Recent Updates In Lecanemab

 Lecenimab-irmb is the generic name for lecanemab. The mouse IgG1 monoclonal antibody has been humanized.  It targets combined soluble and insoluble forms of amyloid \ (A\).  Amyloid \ is lowered in a dose-dependent way.

The medication binds to amyloid \, increasing its clearance and decreasing amyloid \ deposition while also decreasing peripheral sink.  In 2023, the FDA authorized lecanemab for the treatment of mild cognitive impairment or mild dementia in Alzheimer's patients.

The label notes that no safety or efficacy information is available for starting treatment earlier or later in the condition than what was investigated. Based on clinical data indicating drug effects on a surrogate endpoint such as, the accelerated approval pathway permits the FDA to approve pharmaceuticals for serious conditions in cases with unmet medical needs. Amyloid plaques in the brain are decreasing when individuals take lecanemab, which is probably going to indicate a positive therapeutic outcome for them.

A parallel-group, double-blind, placebo-controlled trial was conducted to determine the dosage for 856 Alzheimer's patients.  The initiation of treatment was observed in individuals exhibiting moderate dementia or motor cortex impairment, and it verified the existence of amyloid \ pathology.

 Every two weeks, the patients got 10 mg/kg of lecanemab.  From baseline to week 79, there was a notable dose- and time-dependent decrease in amyloid \ plaques, as compared to the placebo arm.

The FDA mandated that the applicant perform a clinical trial, or confirmatory study, to confirm projected clinical benefits as a post-marketing requirement of fast approval. The findings of study 301, or the CLARITY AD trial, were used to assess the effectiveness of lecanemab.

Study 301 (CLARITY AD)

Research 301 is a multicenter, parallel-group, randomized, double-blind, placebo-controlled research that included 1795 Alzheimer's patients.
A dosage of 10 mg/kg was given every two weeks.  Compared to placebo, there was a clinically significant decrease in decline from baseline to 18 months, and the results were statistically significant.

 The FDA changed Lecanemab's approval status to traditional on July 6, 2023, after the confirmatory trial confirmed the drug's therapeutic benefit.

The first amyloid \-directed antibody to transition from accelerated to traditional approval for Alzheimer's disease treatment is lecanemab.

Aducanumab

 A human immunoglobulin gamma 1 (IgG1) monoclonal antibody is called audatenumab.  The approval was given in June 2021. The first authorized IV amyloid-directed monoclonal antibody is this one.  The FDA has approved it for Alzheimer's disease patients with mild cognitive impairment or mild dementia.  The IV approach is used to administer it.

Lecanemab Side Effects

Amyloid-related imaging abnormalities (ARIA), headache, and responses linked to infusion are the most frequent adverse effects of lecanemab.  Nausea, vomiting, changes in blood pressure, and influenza-like symptoms are among the responses linked to the infusion.

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Amyloid-related Imaging Abnormalities

The most typical presentation of ARIA is transient swelling in the brain regions shown in imaging studies, such as ARIA-E, which indicates sulcal effusion or edema.It may be accompanied by little areas of bleeding within or on the surface of the brain, although it normally goes away with time.  ARIA-H is hemosiderin deposition, which comprises superficial sclerosis and microhemorrhage. ARIA can develop on its own in Alzheimer's patients.  ARIA-H and ARIA-E are typically associated.

 The most typical presentation of ARIA is transient swelling in the brain regions shown in imaging studies, such as ARIA-E, which indicates sulcal effusion or edema.It may be accompanied by little areas of bleeding within or on the surface of the brain, although it normally goes away with time.  ARIA-H is hemosiderin deposition, which comprises superficial sclerosis and microhemorrhage.

ARIA can develop on its own in Alzheimer's patients.  ARIA-H and ARIA-E are typically associated.  According to the prescribing advice, to determine the risk of developing ARIA, an Apo E4 status test should be carried out prior to beginning Lecanemab medication.

In the event that genetic testing is not carried out, patients may still get Lecanemab treatment. It is unknown, nevertheless, if they are homozygotes for APOE E4 and thus more susceptible to ARIA.  Compared to placebo, the use of anticoagulants in conjunction with lecanemab may be linked to a higher incidence of intracerebral hemorrhages.

 When prescribing Lecanemab to individuals who are on anticoagulants or who have other risk factors for intracerebral hemorrhage, caution should be exercised.  The patient's history of severe hypersensitivity to lecanemab-irmb or its inactive components is a significant contraindication.  Adverse responses can happen, including swelling or allergic reactions that cause anaphylaxis, or angioedema.

Administration

 It comes in a single dose vial containing 500 mg of lecanemab-irmb per 5 ml or 200 mg per 2 ml, or 100 mg per ml; it is administered as an IV infusion.  The medication needs to be diluted before being taken.
The patient is infused with the Lecanemab-irmb solution after it has been introduced to an infusion bag holding 250ML of 0.9% sodium chloride injection.

Recommended Dosage

 Once every two weeks, an IV infusion lasting about an hour should be administered at a dose of 10 milligrams per kilogram after it has been diluted. The dose that is advised for patients with ARIA-E and ARIA-H is contingent upon the severity of their radiographs and their clinical symptoms.

Since lecanemab targets these A\ deposits, it is important to confirm the existence of amyloid \ pathology prior to starting this medication.
To assess for ARIA, a recent MRI taken within the previous year is requested. An MRI is also necessary prior to the fifth, seventh, and fourteenth injections.

Genetic testing can also be used to assess an individual's APOE E4 status and ARIA risk.

Premedication/ Prophylaxis

Acetaminophen, corticosteroids, NSAIDs, and antihistamines may be used as part of a premedication regimen.  It may also be taken into consideration if a prior infusion-related response occurred.

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Therapy Interruption For Toxicity

It could be necessary to stop therapy due to toxicity in cases of ARIA-E, ARIA-H, and intracerebral hemorrhage.  The MRI radiological results and clinical symptom severity are used to determine which patients have ARIA-E, or edema. The patient may be asymptomatic, have mild, moderate, or severe symptoms, depending on the clinical severity.

In a similar vein, an MRI can have mild, moderate, or severe severity. Dosing can continue if the MRI results are mild and the patient is asymptomatic; if the patient has mild symptoms, dosing can also continue based on the clinician's opinion. When the clinical symptoms are moderate to severe or the MRI results indicate moderate or severe disease, the dosage should be stopped.

 In ARIA-H, if the patient is asymptomatic and the MRI results are not too high, the medication is nevertheless administered.  If the patient exhibits symptoms or if the MRI shows moderate to severe abnormalities, the dose is stopped.  If the patient experiences intracellular hemorrhages larger than one centimeter in diameter while receiving treatment, the dosage should be stopped until the MRI shows signs of radiological stabilization and any residual symptoms have disappeared.  No precise dose recommendations based on renal or hepatic impairment exist; the decision to stop taking the medicine or continue therapy will be made based on clinical judgment.

Pharmacokinetics

After six weeks of treatment, the steady-state concentration is attained.

Metabolism

That's an antigen. As a result, the proteolytic enzymes break it down similarly to how endogenous IgGs do. After five to seven days.

Retirement

It is recommended that the unopened vials not be frozen or shaken, and that they be kept between 2 and 8 degrees Celsius in their original box to protect them from light. It is advised that the diluted solution be used right away. It can be kept at room temperature for up to 4 hours or in the refrigerator for up to 2 degrees, provided it is not taken right away.
It ought not to be kept frozen. Before administering, it should come to room temperature if it has been refrigerated.

Hope you found this blog helpful for your Psychiatry residency Neurology and General Medicine preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.