Longeveron's Cell Therapy Lomecel-B Improves Cognitive Function in Mild Alzheimer Disease
The study included 48 patients, 36 of whom received laromestrocel and 12 of whom received a placebo.
Joshua M. Hare, MD, FACC, FAHA
New data from the now-completedphase 2a CLEAR MIND trial (NCT05233774), which is evaluating Longeveron's allogeneic bone marrow-derived medicinal signaling cell (MSC) formulation Lomecel-B (also known as laromestrocel) for the treatment of mild Alzheimer disease (AD), have been published in Nature Medicine.1 Among the findings reported were improvements in cognitive function, quality of life, and brain volume.
The study included 48 patients, 36 of whom received laromestrocel and 12 of whom received a placebo. Longeveron reported that laromestrocel treatment was associated with a slowing in cognitive and functional decline. This finding was informed by statistically significant data from the Montreal Cognitive Assessment, as well as statistical trending improvements, made with comparison to the placebo group, on the Clinical Dementia Rating – Sum of Boxes (CDR-SB) and Mini-Mental State Examination (MMSE). Furthermore, Longeveron noted that on the Composite Alzheimer’s Disease Score (CADS), an improvement from baseline at 39 weeks posttreatment was recorded.
In addition, the company stated that on the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL), a statistically significant improvement was seen for the laromestrocel group in relation to the placebo group. Statistically significant data indicating that total brain volume, hippocampus volume, temporal and frontal lobe volumes, and thalamus volume losses had been minimized in the laromestrocel group compared to the placebo group were also noted. Improvements for the laromestrocel group in comparison to the placebo group were also observed on the the Alzheimer’s Disease Related Quality of Life (ADRQOL) and Quality of life AD (QOL-AD) scales.
With regard to safety, Longeveron characterized the cell therapy as “well-tolerated” in the trial, regardless of whether it was delivered in single or multiple dosing regimens. No events of hypersensitivity, infusion-related reactions, or amyloid-related imaging abnormalities were reported.
“This Nature Medicine publication reinforces laromestrocel’s safety and efficacy as a potential treatment for mild AD and paves the way for more advances in utilizing cell therapy for AD,” Joshua Hare, MD, the founder and chief science officer of Longeveron, said in a statement.1 “As a mesenchymal stem cell therapy that has multiple potential mechanisms of action to address inflammatory responses in the brain, laromestrocel offers a new potential strategy to address the underlying pathology of AD without the limitations of previous therapies. Cell based therapy with MSCs is a particularly attractive treatment candidate as it encompasses pro-vascular, immunomodulatory, and tissue repair mechanisms of actions, with findings validated in a murine AD model.”
CLEAR MIND was open to participants with mild AD and who were aged 60 to 85 years. In order to be included, patients were required to have scored 18 to 24 on the MMSE and to show consistency with AD on a brain MRI and positron emission tomography (PET) scan.
“This study had limitations that warrant mentioning,” first author Brian G. Rash, the vice president of research and discovery at Longeveron, and colleagues wrote in the Nature Medicine paper’s Discussion section.2 “First, there was a relatively small sample size with a high proportion of patients of Hispanic ethnicity and some variables such as patient education level were not ascertained. Second, the 39-week study duration was relatively short for trials of disease-modifying agents in the early AD patient population, and longer studies are warranted. Additionally, while global statistical testing principles support using a composite end point in small studies for AD, the CADS used here is not a validated composite end point and it should be assessed with future studies.”
“Taken together, the findings of this study suggest that treatment of patients with mild AD with laromestrocel is safe, administered in both single and multiple dosing regimens,” Rash and colleagues continued. “New studies using laromestrocel in the treatment of mild AD will examine the safety and efficacy profile of extended treatment durations and follow-up periods with greater statistical power, and we hypothesize longer treatment duration would slow AD progression further. The safety results presented here, coupled with signals of potential efficacy, support ongoing clinical development of this novel class of therapeutics for AD.”
CGTLive® previously spoke to Hare at the 2024 Alzheimer’s Association International Conference (AAIC), held July 28-August 2nd in Philadelphia, Pennsylvania, about earlier data from CLEAR MIND that was presented at that meeting.3 In the interview, he emphasized the promising safety profile of laromestrocel.
“The one thing I do want to emphasize is the safety profile,” Hare told CGTLive. “Other classes of drugs produce a condition called Alzheimer's related imaging abnormality (ARIA). It was first detected on MRI and it corresponds to either brain edema or hemorrhage in the brain, and it can be clinically significant. This is a concern. We're developing classes of drugs that are effective but also have a high risk factor profile. So we were very pleased with Lomecel-B, there's no evidence of ARIA. The risk profile is excellent because the risk is so low of the Lomecel-B infusions. One of the key things that we did in the study, just to emphasize, is repeat dosing. Recurrent dosing with Lomecel-B is just as safe as a single administration.”
