Background

Lomecel-B is a preparation of multipotent stem and progenitor cells isolated from donated bone marrow of young healthy adults, and expanded in culture. The cells are administered by intravenous infusion and are claimed to travel to sites of tissue damage to quell inflammation and stimulate repair. These allogeneic cells do not need to be immunologically matched to recipients, and have been shown safe in several conditions (e.g., see Thompson et al., 2020). 

In preclinical work in Alzheimer's disease mouse models, systemically infused mesenchymal stem cells were reported with varying efficacy to cross the blood-brain barrier, inhibit Aβ deposition and tau phosphorylation, promote Aβ clearance, neurogenesis, and improve memory performance (e.g., Neves et al., 2021). In one study, the cells decreased inflammation and released chemoattractants that recruited microglia to clear Aβ (Lee et al., 2012).

Findings

In October 2016, Longeveron began a Phase 1 study funded by the Alzheimer’s Association. At three sites in Florida, 32 people with clinically diagnosed Alzheimer’s disease and PET evidence of brain amyloid were randomized 2:2:1 to receive a single infusion of 20 million or 100 million cells or placebo, and then followed up for one year. The primary outcome was safety; secondary endpoints included a battery of neurological, cognitive, and quality-of-life assessments, plus blood and CSF inflammatory and AD biomarkers. The study was completed in September 2021; results were published after peer review (Brody et al., 2022). No adverse effects were seen related to treatment. ARIA was not observed. One patient who withdrew from the study died 20 weeks after the infusion. The study was not powered to show efficacy; even so, the company reported improvements compared to placebo in biomarkers of inflammation and vascular function, a transient increase in hippocampal volume, and, in the low-dose group, some slowing of decline on cognitive and functional measures.

In December 2021, the company began a 48-person Phase 2a study. Participants have mild Alzheimer’s disease, with MMSE scores between 19 and 23, and positive amyloid PET scans. Four groups of 12 patients each received one or four infusions of 25 million cells, four infusions of 100 million cells, or placebo, over a span of 12 weeks. The primary outcome was safety, with monitoring for six months for adverse events, including MRI for ARIA and microhemorrhages. As a secondary outcome, the trial registry listed changes in the ADAS-Cog13 and MMSE. This trial occurred at two sites in Miami, and was completed in September 2023.

On October 5, 2023, the company announced top-line results (press release). The treatment met the safety endpoint; no ARIA or microhemorrhages were detected. According to the release, serious adverse events in three patients were judged to be unrelated to the drug. On secondary outcomes, the company claimed a statistically significant improvement among the lowest-dose group on the Composite Alzheimer Disease Score. The CADS is made up of the ADAS-cog-13, ADCS-ADL, CDR-SB, and left hippocampal volume. Data were not shown for other doses. According to a company presentation at the 2024 AAIC, the lowest (single-) dose group improved slightly on the CADS, while the placebo-treated patients declined. The difference, less than 0.5 points, was significant at the p<0.1 prespecified threshold. In the multidose groups, CADs was unchanged from baseline, and not different from placebo. The rate of hippocampal volume loss on MRI and inflammation per diffusion tension imaging were both reduced in treated groups, though not all changes were statistically significant.

Lomecel-B is also in clinical trials for congenital heart malformation, and aging-related frailty (pipeline; see also Yousefi et al., 2022). Outside of these trials, patients with frailty, mild cognitive impairment, Alzheimer’s, and related dementias, or osteoarthritis can receive Lomecel-B infusions at their own expense, as part of a treatment registry study in the Bahamas. Lomecel-B is not an approved treatment in the U.S.

For all trials of Lomecel-B, see clinicaltrials.gov.