Source: Cell plus

New clinical data show that the drug Lomecel-B™, derived from bone marrow mesenchymal stem cells, improves several measures of cognitive function in a dose-dependent manner;

Caregiver scores indicated an improvement in quality of life for patients treated with Lomecel-B™;

Magnetic resonance imaging biomarker study data show that Lomecel-B™ reduces brain volume loss in multiple regions associated with Alzheimer's disease, reduces neuroinflammation, and improves cerebral blood flow;

The overall results confirm the therapeutic potential of this drug product in the treatment of mild Alzheimer's disease and support further development.

According to a recent announcement by Longeveron, the company has supplemented the data from the CLEAR MIND2 clinical trial. Preliminary results released last time are as follows:

Based on statistical and clinical evaluation, the trial met its primary endpoint of safety.

Compared with placebo, patients receiving single and multiple doses of Lomecel-B achieved statistical significance in the trial's secondary endpoint, the combined Alzheimer's disease score (CADS).

In other analyses of cognitive function and daily living data, Lomecel-B™ has a favorable dose-response effect compared to placebo, and Lomecel-B™ can slow some measures of cognitive function (MoCA, MMSE) and in some cases improve some measures of cognitive function. A new analysis of imaging data measured using magnetic resonance imaging (MRI) shows that taking Lomecel-B™ reduces neuroinflammation, as assessed by diffusion tensor imaging (DTI), and also counteracts brain volume loss in Alzheimer's disease associated regions (TBV, hippocampus, ventricle, thalamus).

Wa'el Hashad, CEO of Longeveron, commented: "These new data support the preliminary results from CLEAR MIND that we published in October and further validate the safety and therapeutic potential of Lomecel-B™ for mild Alzheimer's disease. We believe that these new data provide evidence for the mechanism of action of Lomecel-B and provide a solid foundation for further research into Alzheimer's disease and other indications." We expect to present CLEAR MIND's research at a major medical meeting in 2024.

Summary of new findings

The latest data further support previous findings that Lomecel-B has the potential to prevent cognitive decline and improve quality of life. In addition to these clinical findings, brain imaging revealed improvements in brain structure as measured by volumetric magnetic resonance imaging and DTI.

The single-dose Lomecel-B™ (25M x 1 dose, p=0.009) and multi-dose treatment groups (25M x 1 dose, 25M x 4 dose, 100M x 4 dose, p=0.015) showed statistically significant improvements relative to placebo on the Montreal Cognitive Assessment (MOCA).

Lomecel-B™ showed a dose-dependent improvement on mini-mental status examination (MMSE) compared to baseline (mean + scale increase at highest dose: 3.0+3.6, 39 weeks, P=0.028)

Lomecel-B™ (100M x 4 doses) showed a higher level of improvement in quality of life observed by caregivers (as measured by the Alzheimer's Disease-Related Quality of Life Scale (ADRQOL)).

Neuronal loss in Alzheimer's disease leads to a common feature of the disease, such as progressive atrophy, resulting in reduced brain volume and cortical thickness, which can be measured by volumetric magnetic resonance imaging. The loss of brain tissue appears first as a shrinking of the structure of the temporal lobe (such as the hippocampus), followed by a shrinking of other parts of the brain (parietal, frontal).

Lomecel-B™ (100M x 4 dose) reduces total brain volume loss by 49% (p=0.034)

Compared with placebo, Lomecel-B™ (25M x 1 dose, p=0.015) and combination treatment groups (25M x 1 dose, 25M x 4 dose, 100M x 4 dose, p=0.038) There was a statistically significant reduction in volume loss in the left hippocampus at week 39 (84% for the 25M x 1 dose).

Compared with placebo, the Lomecel-B™ (100M x 4 dose) dose group had a 20% and 33% reduction in brain volume retention at week 39, respectively.

Compared with placebo, all Lomecel-B™ dose groups had lower levels of neuroinflammation as measured by DTI at week 39.

Taken together, the Company believes that the results of the CLEAR MIND study provide a solid foundation for further development of treatments for patients with mild Alzheimer's disease.

About the CLEAR MIND study

The trial was designed to investigate the effect of Lomecel-B™ on mild Alzheimer's disease: a randomized, double-blind, placebo-controlled Phase 2 trial (NCT05233774) called the CLEAR MIND trial.

The trial enrolled a total of 50 patients between the ages of 60 and 85 who had been diagnosed with mild Alzheimer's disease according to National Institutes of Health-Alzheimer's Association (NIA-AA) criteria with a mini-Mental State Examination (MMSE) score of 18 to 24. Brain magnetic resonance imaging (MRI) and positron emission tomography (PET) scans showed results consistent with Alzheimer's disease.

The trial was designed to test three different dosing regimens of Lomecel-B™ versus placebo, with patients randomly assigned in a 1:1:1:1 ratio. The following doses were studied: Lomecel-B™ was administered at 25 x 10^6 cells (25 m) on day 0, followed by placebo infusion at weeks 4, 8, and 12; The Lomecel-B™ dose was 25M and was administered four times on day 0, week 4, week 8, and week 12. The Lomecel-B™ dose was 100 x 106 cells (100M) and was administered on day 0, week 4, week 8, and week 12 for a total of 4 doses.

The primary endpoint of the trial was safety, as measured by the occurrence of serious adverse events (SAEs) within 30 days of each dosing. Safety data were consistent with previously known safety profiles, with no hypersensitivity reactions, infusion-related reactions, no cases of Alzheimer's disease associated edema (ARIA-E) or microbleeding (ARIA-H) and superficial siderosis on magnetic resonance imaging (MRI), and no significant changes in laboratory evaluation and electrocardiogram (EKG).

Given the study sample size (N=49 patients), the study employed a novel global statistical test called the Alzheimer's Disease Composite Score (CADS), which has been accepted by the scientific community and is increasingly used in Alzheimer's clinical trials. CADS was the secondary outcome measure of the trial, combining cognitive, functional, and brain magnetic resonance imaging information.

The secondary endpoint was defined as the change in CADS from baseline to week 39. The score was composed of ADAS-cog-13, ADCS-ADL, CDR-SB, and left hippocampal volume (normalized intracranial volume).

In the efficacy analysis, the secondary endpoint was tested using a pre-specified bilateral α0.1. If the statistical significance of any dose comparison reaches this level, the study is considered positive and supports further investigation of Lomecel-B™ in larger, higher power studies. The individual components of CADS were evaluated with a bilateral alpha of 0.05.

Exploratory endpoints included cognitive assessment (MMSE, MOCA), quality of life (ADRQOL), brain volume measurement (vMRI), other imaging modalities, and biomarkers related to inflammation and vascular function.