Our newest research-advisor Prof. Randall J. Bateman, MD.
Leqembi FDA Approval
Pat & Dennis Bender Early Dementia Diagnosis & Prognosis Fund
J. Dennis Bender
Office, Home & Cell Phone: 859-391-5226
5726 La Jolla Blvd. – Suite 311
La Jolla, CA 92037-7345
&
Office - 100 Riverside Pl. - Suite 303
Covington, KY 41011-5711
We support the development of improved diagnostic methods for the early detection and diagnosis of MCI, Alzheimer’s, vascular and other dementias, their likely prognosis, and best treatment. We focus on the development of Bayesian-based medical-decision-support systems, comparative-effectiveness research, and the better utilization of these for the above. (After incorporating in KY as a 501(c)(3) in 2002, we dissolved that entity for a simplified form of two entirely self-financed, private philanthropies utilizing a Vanguard Charitable Trust for making annual-research-grants for early-dementia-detection and its correct differential-diagnosis and likely-prognosis. They will continue on, after I am gone, either mentally or physically. Prof. Randall Bateman is the first of our fund’s research advisors.
See: https://www.alz.org/alzheimers-dementia/research_progress/earlier-diagnosis )
www.JDBender.com – EMS/eVTOL Experimental Aviation Fund (Vanguard Charitable Trust)
www.JDBender.org – Dementia Diagnosis Fund (Vanguard Charitable Trust)
“Today’s action is the first verification that a drug targeting the underlying-disease-process of Alzheimer’s-disease has shown clinical-benefit in this devastating disease. This confirmatory-study verified that it is a safe and effective treatment for patients with Alzheimer’s-disease. . . Leqembi should be initiated in patients with mild-cognitive-impairment or mild-dementia-stage-of-Alzheimer’s-disease, the population in which treatment was studied in clinical-trials.”
Hurray! A perfect note to leave on as I take-off for Chandler, AZ to look at one of the 3 ultralights I’m considering for a donation to the S.D. Air & Space Museum and my trip back to Covington, KY for the summer.
FDA Converts Novel Alzheimer’s-Disease Treatment to Traditional-Approval
Action Follows Confirmatory Trial to Verify Clinical-Benefit
For Immediate FDA Release: July 6, 2023
Today, the U.S. Food and Drug Administration converted Leqembi (lecanemab,) indicated to treat adult-patients with Alzheimer’s-disease, to traditional-approval following a determination that a confirmatory-trial-verified-clinical-benefit. Leqembi is the first amyloid beta-directed antibody to be converted from an accelerated approval to a traditional approval for the treatment of Alzheimer’s disease. The drug works by reducing amyloid plaques that form in the brain, a defining pathophysiological feature of the disease.
Leqembi was approved in January under the Accelerated-Approval-pathway. This pathway allows the FDA to approve drugs for serious conditions where there is an unmet-medical-need, based on clinical-data demonstrating the drug’s effect on a surrogate-endpoint—in the case of Leqembi, reducing-amyloid-plaques-in-the-brain—that is reasonably-likely to predict-a-clinical-benefit-to-patients. As a post-marketing requirement of the accelerated-approval, the FDA required the applicant to conduct a clinical-trial, often referred to as a confirmatory-study, to verify-the-anticipated-clinical-benefit-of-Leqembi. Efficacy of Leqembi was evaluated using the results of Study-301 (CLARITY-AD), a Phase-3 randomized, controlled clinical-trial.
“Today’s action is the first verification that a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit in this devastating disease,” said Teresa Buracchio, Acting Director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “This confirmatory-study verified that it is a safe-and-effective treatment for patients with Alzheimer’s-disease.”
Alzheimer’s-disease is an irreversible, progressive brain disorder affecting more than 6.5 million Americans. The disease slowly destroys memory and thinking skills and eventually, the ability to carry out simple tasks. While the specific causes of Alzheimer’s are not fully known, it is characterized by changes in the brain—including the formation of amyloid-beta-plaques and neurofibrillary, or tau-tangles—that result in loss-of-neurons and their connections.
Study-301 was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that enrolled 1,795 patients with Alzheimer’s-disease. Treatment was initiated in patients with mild-cognitive-impairment or mild-dementia-stage-of-disease and confirmed-presence-of-amyloid-beta-pathology. Patients were randomized in a 1:1 ratio to receive placebo or Leqembi at a dose of 10-milligrams (mg)/kilograms (kg), once-every-two-weeks. Leqembi demonstrated a statistically-significant and clinically-meaningful reduction-of-decline-from-baseline-to-18-months on the primary-endpoint, the Clinical-Dementia-Rating-Scale-Sum-of-Boxes-score, compared to placebo. Statistically-significant-differences between treatment-groups were also demonstrated-on-all-secondary-endpoints, which included the Alzheimer’s-Disease-Assessment-Scale-Cognitive-Subscale-14, and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale for Mild-cognitive-impairment.
On June 9, the FDA convened the Peripheral and Central Nervous System Drugs Advisory Committee to discuss whether Study-301 provided evidence-of-clinical-benefit-of-Leqembi-for-the-treatment-of-Alzheimer’s-disease. All committee-members voted affirmatively that the results of the study verified the clinical-benefit of Leqembi for the indicated-use.
The most-common-side-effects of Leqembi were headache, infusion-related-reactions and amyloid-related-imaging-abnormalities (ARIA), a side-effect known to occur with the class-of-antibodies-targeting-amyloid. ARIA most-commonly presents as temporary-swelling in areas-of-the-brain seen on imaging-studies that usually resolves-over-time and may be accompanied by small-spots-of-bleeding in or on the surface-of-the-brain. Although ARIA is often not associated with any symptoms, symptoms can occur and include headache, confusion, dizziness, vision changes and nausea. ARIA can also infrequently present with serious and life-threatening brain-edema that can be associated with seizures and other severe-neurological-symptoms. Intracerebral-hemorrhages can occur in patients treated with this class of medications and can be fatal. A boxed-warning is included in the prescribing information to alert patients and caregivers to the potential-risks-associated-with-ARIA.
Patients treated with Leqembi who are homozygous-for-the-ApoEε4-allele have a higher-incidence-of-ARIA, including symptomatic, serious and severe ARIA, compared to heterozygotes and noncarriers. The prescribing information states that testing-for-ApoEε4-status should be performed before starting treatment with Leqembi to inform-the-risk-of-developing-ARIA.
Use of anticoagulant-medication was associated with an increased number of intracerebral-hemorrhages in patients taking Leqembi compared to placebo. The prescribing information recommends caution when considering use of Leqembi in patients taking anticoagulants or with other risk-factors-for-intracerebral-hemorrhage.
Leqembi is contraindicated in patients with serious-hypersensitivity-to-lecanemab or to any of its inactive-ingredients. Adverse-reactions may include angioedema (swelling) and anaphylaxis (allergic reaction).
Leqembi should be initiated in patients with mild-cognitive-impairment or mild-dementia-stage-of-Alzheimer’s-disease, the population in which treatment was studied in clinical-trials. The labeling states that there are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.
The approval of Leqembi was granted to Eisai Inc.
[Keywords and compound-keywords (tags) are highlighted-and-hyphenated in italic-and-bold; place-names, organizations and titles are in bold; media-names put in italic. Instead of underlining, I’ve been experimenting with hyphenating entire phrases – long-tail-keywords. This odd style was being tried to enhance generative-AI processing and ease-of-spotting items-of-interest in my specific website-achieved documents. Now experimenting with generative-AI to eliminate this time-consuming distraction.]
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