Three-Year Long-Term Data for Eisai/Biogen’s Alzheimer’s Therapy Leqembi and Positive Interim Results for Lexeo’s Gene Therapy LX1001 Announced

Nov 01, 2024 07:43 CST Updated 07:43

Eisai

Pharmaceutical Product R&D and Manufacturer

Biogen

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LEXEO Therapeutics

Clinical-Stage Gene Therapy Developer

▎WuXiEdited by the Kant Content Team

Eisai/Biogen Alzheimer's Disease Therapy 3-Year Long-Term Data Released

Eisai and Biogen recently announced that the latest clinical trial results of the anti-β-amyloid (Aβ) antibody drug Leqembi (lecanemab) for the treatment of early Alzheimer's disease (AD) have been released at the Clinical Trials on Alzheimer's Disease (CTAD) conference.

The data from the Phase 3 clinical trial Clarity AD presented at CTAD included additional measurements from patients who received continuous treatment with Leqembi for three years and had lower levels of amyloid plaque accumulation in the brain at baseline. The data showed that patients who continued treatment demonstrated improvements across multiple measures assessing cognitive abilities and activities of daily living, such as,33% of patients showed improvement in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score; 43% of patients showed improvement in the Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14) score, which evaluates cognitive abilities; and 48% of patients showed improvement in the Alzheimer’s Disease Cooperative Study – Mild Cognitive Impairment Activities of Daily Living (ADCS MCI-ADL) scale, which assesses daily living abilities.These results suggest that early initiation of Leqembi treatment may positively impact disease progression in patients with little or no tau protein accumulation and low levels of amyloid buildup, potentially offering sustained benefits for early-stage patients in the long term.

Latest Results of Alzheimer's Disease Gene Therapy Report

LEXEO Therapeutics recently announced the development of the gene therapy LX1001 for the treatment ofAPOE4Positive Interim Results from Phase 1/2 Clinical Trial of Alzheimer's Disease. LX1001 treatment showed a dose-dependent increase in APOE2 protein expression and improvement in tau protein biomarkers associated with the disease, which are closely related to cognitive outcomes. LX1001 also demonstrated a favorable safety profile.

LX1001 is an investigational gene therapy based on the AAVrh10 vector, designed to deliver protectiveAPOE2Allele delivery to carriers of twoAPOE4The central nervous system of patients with alleles.APOE2Associated with a significant reduction in the risk of developing Alzheimer's disease and a slowing of disease progression.

Interim data show:

All participants showed an increase in APOE2 protein expression in cerebrospinal fluid (CSF), with a dose- and time-dependent growth, maintaining stability up to 12 months.
Most Participants Show Stable Amyloid Pathology
In more than two-thirds of participants, tau protein biomarkers in CSF (including tau, P-tau181, P-tau217, and P-tau231) consistently showed a decrease compared to baseline and the natural course.
Patients with moderate Alzheimer's disease (n=4) generally showed the most significant improvements across various biomarker endpoints.

The study reported four serious adverse events (SAEs), three of which were considered unrelated to the treatment, and one case of mild to moderate sensorineural hearing loss that was possibly related to the treatment.

Mechanism of Action for Oral Alzheimer's Disease Therapy Clinically Validated

Anavex Life Sciences announced today that the latest analysis of 2b/3 phase clinical trial data shows the mechanism of action of its investigational daily oral therapy blarcamesine in improving outcomes for Alzheimer's patients by activating the SIGMAR1 signaling pathway.

SIGMAR1 is a membrane protein, and blarcamesine induces autophagy by activating SIGMAR1, thereby restoring cellular homeostasis.In patients with Alzheimer's disease, since genetic variations may lead to impaired SIGMAR1 function, patients carrying the unmutated SIGMAR1 wild-type protein are expected to have a stronger response to blarcamesine.

An analysis of the Phase 2b/3 clinical trial confirmed this: at 48 weeks,Based on the primary endpoint ADAS-Cog13 score, blarcamesine significantly slowed patient disease progression by 36.3%. In the SIGMAR1 wild-type patient group, blarcamesine slowed disease progression by 49.8% at 48 weeks.Analysis based on CDR-SB scores also yielded similar consistent results.

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References:

[1] Eisai Presents Data on Benefits of Long-Term Administration of Dual-Acting Lecanemab at the 17th Clinical Trials for Alzheimer's Disease (CTAD) Conference. Retrieved October 31, 2024, from https://www.prnewswire.com/news-releases/eisai-presents-data-on-benefits-of-long-term-administration-of-dual-acting-lecanemab-at-the-17th-clinical-trials-for-alzheimers-disease-ctad-conference-302292163.html

[2] Lexeo Therapeutics Announces Positive Interim Data for LX1001, First-Ever Gene Therapy to Impact the Underlying Genetic Cause of APOE4-Associated Alzheimer’s Disease, at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference. Retrieved October 31, 2024, from https://ir.lexeotx.com/news-releases/news-release-details/lexeo-therapeutics-announces-positive-interim-data-lx1001-first

[3] Anavex’s Blarcamesine Achieves Pre-specified Efficacy in Phase IIb/III Alzheimer’s Trial: Data Presented at CTAD Conference 2024. Retrieved October 31, 2024, from https://www.globenewswire.com/news-release/2024/10/31/2972323/29248/en/Anavex-s-Blarcamesine-Achieves-Pre-specified-Efficacy-in-Phase-IIb-III-Alzheimer-s-Trial-Data-Presented-at-CTAD-Conference-2024.html

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