Lomecel-B Safe, Seems Promising for Alzheimer Disease Measures
There were no serious adverse events related to the cell therapy and no evidence of ARIA.
Wa’el Hashad
Credit: Longeveron
Lomecel-B was well-tolerated in patients with mild Alzheimer disease (AD) receiving up to 4 infusions of the cell therapy and demonstrated some improvements in cognitive function and other disease measures, according to new data from the phase 2a CLEAR MIND trial (NCT05233774).1
These data were presented at the 2024 Alzheimer’s Association International Conference (AAIC), held July 28-August 2nd in Philadelphia, Pennsylvania, by Brian G. Rash, PhD, vice president, research and discovery, Longeveron.
The data are from 49 participants: 12 in the placebo arm, 13 in the low dose arm (1 dose x 25 million), 13 in the low, multi-dose arm (4 doses x 25 million), and 11 in the high, multi-dose arm (4 doses x 100 million). The therapy was well-tolerated, with no serious adverse events (AEs) related to Lomecel-B. Serious AEs that did occur included acute respiratory failure, anemia, lumbar radiculopathy, all of which resolved. There were no early discontinuations of infusion or any evidence of amyloid-related imaging abnormalities (ARIA).1
Investigators found that treated participants had better scores on Composite Alzheimer’s Disease Score (CADS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and AD Cooperative Scale-Activities of Daily Living (ADCS-ADL) than those receiving placebo. Specifically, participants in the high, multi-dose arm performed statistically significantly better on ADCS-ADL (P = .04) than placebo with trends of improvement on MMSE and participants in the low dose arm performed statistically significantly better on MoCA (P = .009) with trends of improvement in CADS at 39 weeks.1
READ MORE: Stephanie Tagliatela on Researching AAV for Lennox-Gastaut, Alzheimer Disease, SCN9a Pain
“There is directional, actual improvement in some of the cognitive scores... not just a slowing of decline, but actually an increase towards the positive direction in the MMSE and the MoCA scores. So, these are very early days, and we don't want to [read too into] it, but we'revery excited about that. Of course, we'll be looking at that very carefully in the next larger study that we do, which will be powered around the efficacy endpoint,” Joshua M. Hare, MD, FACC, FAHA, cofounder, chief science officer, and chairman, Longeveron, and professor of medicine, Miller School of Medicine, University of Miami, told CGTLive®. “If we have an agent here that can actually improve cognitive function in the mild AD patients, that would be a very exciting outcome, one very clinically meaningful for affected patients and their families.”
On volumetric MRI, participants in the high, multi-dose arm (P = .009) and low, multi-dose arm (P = .006) had a statistically significant reduced reduction (up to 49%) in whole brain volume from placebo at 39 weeks, with similar findings in bilateral lateral ventricle volume, hippocampal volume, and medial temporal cortex volume. The investigators also found significant correlations between MMSE and bilateral hippocampal volume (R = .41; P = .008) and between MoCA and whole brain volume (R = .35; P = .025). Lastly, there were trends of improvement on diffusion tensor imaging in treated participants compared to placebo.1
“In recent years, we’ve seen an enhanced industry focus on bringing novel Alzheimer’s Disease therapeutics to market to treat the millions of people who suffer each year,” Nataliya Agafonova, MD, Chief Medical Officer, Longeveron, said in a statement.2 “The emergence of new Alzheimer’s Disease therapies has demonstrated that we are increasingly capable of treating a condition once deemed untreatable, and the next step in this endeavor is to develop a therapeutic that is both safe and effective in treating this disease. The results from the Phase 2a CLEAR MIND trial are highly encouraging and demonstrate the potential of Lomecel-B™ to fulfill this need, and I look forward to its continued development.”
Lomecel-B is an allogeneic medicinal signaling cell therapy product. Longeveron recently received both Fast Track and Regenerative Medicine Advanced Therapeutic (RMAT) Designations for Lomecel-B3 and will be meeting with the FDA in a Type B meeting to inform trial design for its anticipated pivotal trial.
