PHILADELPHIA — An experimental, cell-based therapy met its primary safety and secondary efficacy endpoints in a phase 2a study on mild Alzheimer's disease (AD).
The results "exceeded our expectations" in terms of "consistent positive efficacy signals" across different domains, including cognition, quality of life, and neuroimaging results, Joshua Hare, MD, co-founder, chief science officer, and chairman of Longeveron, which developed the treatment, told Medscape Medical News.
The findings were presented on July 28 at the Alzheimer's Association International Conference (AAIC) 2024.
FDA Fast Track Designation
Earlier this month, the US Food and Drug Administration (FDA) granted Lomecel-B Regenerative Medicine Advanced Therapy designation and Fast Track designation for the treatment of mild AD.
Lomecel-B is a living cell product made from medicinal signaling cells isolated from the bone marrow of young, healthy, adult donors. These specialized cells have been shown to perform a number of complex functions in the body, including the formation of new tissue. They also have been shown to respond to sites of injury or disease and secrete bioactive factors that are immunomodulatory and regenerative.
Lomecel-B may have multiple potential mechanisms of action that could lead to anti-inflammatory and provascular regenerative responses "and therefore may have broad application for a range of rare and aging related diseases," a company press release noted.
In a phase 1 study, a single dose of Lomecel-B had a positive benefit/risk profile and suggested clinical benefits in cognitive function and in offsetting hippocampal atrophy.
The phase 2a CLEAR MIND study tested single and multiple dosing regimens of Lomecel-B vs placebo in 48 patients, aged 60-85 years, with a diagnosis of mild AD by National Institutes of Health-Alzheimer's Association criteria, a Mini-Mental State Examination (MMSE) score of 18-24, and a brain MRI and PET scan consistent with AD.
On the primary outcome of safety, the study confirmed the established safety profile of Lomecel-B for single and multiple dosing regimens, with no hypersensitivity or infusion-related reactions and no cases of amyloid-related imaging abnormalities.
On the secondary efficacy measures, treatment with Lomecel-B was associated with an overall slowing of disease worsening compared with treatment with placebo.
"Positive efficacy results were demonstrated via a change from baseline at week 39 of the trial at prespecified levels using the Composite Alzheimer's Disease Score (CADS) — a secondary outcome measure that combines information across cognitive, functional capacity, and brain MRI domains," the company reported in a press release.
Lomecel-B was also associated with slowing cognitive and functional decline as shown by statistically significant results in the Montreal Cognitive Assessment and "statistical trending" improvements compared with placebo in Clinical Dementia Rating-Sum of Boxes and MMSE.
A statistically significant improvement relative to placebo was observed in the AD Cooperative Study-Activities of Daily Living, and there was a numerical improvement relative to placebo in quality of life observed by caregivers and measured by AD-Related Quality of Life and Quality of Life-AD scales.
Lomecel-B also appeared to slow the progression of brain atrophy in areas associated with AD, which was statistically significant for left hippocampal volume, relative to placebo, and this correlated with clinical outcomes.
"The detailed measurement of brain atrophy shows that there's a marked attenuation of the degree of atrophy that develops after treatment," said Hare.
Targeting Neuroinflammation
In addition, findings on diffusion tensor imaging MRI suggest that Lomecel-B has the potential to reduce neuroinflammation compared with placebo.
"This cellular-based therapy is highly effective at targeting neuroinflammation devoid of the side effects of most other anti-inflammatory therapies. Of course, we need to do more studies, but the results of diffusion tensor imaging were incredibly consistent that there was a powerful effect to reduce neuroinflammation," Hare said.
The company plans to meet with the FDA shortly to iron out details of the next study. "We have a slight signal that multiple dosing is better than single dosing. One of the primary objectives of the next study that we're planning will be to further nail down dosing regimens," Hare said.
Commenting on this research for Medscape Medical News, Heather M. Snyder, PhD, senior vice president of medical and scientific relations, Alzheimer's Association, said, "This is an interesting small study of a promising new approach to Alzheimer's treatment."
"The Alzheimer's Association funded some of the prior work leading to this study through the Part the Cloud research funding initiative. The data reported at AAIC 2024 are encouraging but preliminary and need to be replicated in larger studies including representative study populations," Snyder said.
"All evidence-based paths to treatment of Alzheimer's and all other dementias should be explored. We are in an era of unprecedented promise, with new treatments in various stages of development that slow, or may possibly prevent, cognitive decline due to Alzheimer's or other disease," she said.
"The Alzheimer's Association envisions a future where there are many treatments available that address these diseases in multiple ways and can be combined into powerful combination therapies, most likely in conjunction with brain-healthy lifestyle guidance," she added.
Note: This article originally appeared on Medscape.
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