Longeveron’s Stem Cell Therapy Shows Potential in Phase 1 Trial

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by Patricia Inacio PhD |

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Longeveron’s Lomecel-B, an investigational bone marrow-derived medicinal signaling cell (MSC), showed an ability to slow cognitive decline and the loss of daily life abilities in patients with mild Alzheimer’s disease relative to those given a placebo in a Phase 1 clinical trial, the company announced.

Treatment with Lomecel-B was deemed safe, with the therapy meeting the trial’s primary safety goal and also improving patients’ quality of life.

The levels of several biomarkers for generating new blood vessels and anti-inflammatory markers also increased significantly with Lomecel-B treatment.

Results of the Phase 1 trial support the potential of Lomecel-B for Alzheimer’s patients. A follow-up Phase 2 study is scheduled to begin by the end of this year, according to Longeveron.

“We are pleased and encouraged by the results of this study, which indicate preliminary safety, and potential efficacy of Lomecel-B in mild Alzheimer’s disease, and we look forward to initiating our Phase 2 trial in the second half of this year,” said Geoff Green, CEO of Longeveron.

“The results are encouraging that Lomecel-B has potential to eventually become a safe and effective treatment for AD,” added Gary Small, MD, of Hackensack Meridian Health, in New Jersey, and a member of Longeveron’s Alzheimer’s disease Program Steering Committee.

Longeveron’s Lomecel-B MSCs are stem cells derived from the bone marrow of young, healthy donors. This type of cell is thought to promote tissue repair, organ maintenance, and immune system function. As such, Longeveron believes that Lomecel-B can address multiple features of Alzheimer’s, including reducing brain inflammation, improving the function of blood vessels in the brain, reducing brain damage due to disease progression, and promoting regenerative responses.

The Phase 1 trial (NCT02600130) — supported by a $3 million Alzheimer’s Association grant — enrolled 33 patients with mild disease at different Florida trial sites.

Participants were assigned randomly to one of three groups — low-dose (15 patients) or high-dose (10 patients) Lomecel-B, or placebo (eight patients). Those in the low-dose group received 20 million MSCs, while the high-dose group received 100 million cells. The placebo group was given a solution that mimics human plasma. The treatments were delivered intravenously.

The trial’s main goal was to assess the safety of Lomecel-B 30 days after infusion. Secondary efficacy goals included neurological, neurocognitive, and quality-of-life assessments.

Within one year after infusion, Lomecel-B was well-tolerated with no treatment-related serious adverse events, including amyloid-related imaging abnormalities — a type of brain swelling often associated with amyloid-targeting therapies — as assessed by MRI scans.

Scores on the Mini‐Mental State Examination — a measure of cognitive abilities — declined faster in the placebo group compared to the low-dose Lomecel-B. At 13 weeks post-infusion, the scores remained significantly higher (indicative of better cognition) in the low-dose Lomecel-B group versus the placebo group.

Within 26 weeks post-infusion, patients in the low-dose Lomecel-B group had significantly better quality of life, as assessed by the Quality of Life in Alzheimer Disease score (higher scores) compared to the placebo group.

Patients’ ability to go about daily life activities, measured using the Alzheimer’s disease cooperative study-activities of daily living, also was significantly better in the low-dose Lomecel-B versus the placebo group.

“I am excited about the potential for this new approach to the treatment of Alzheimer’s disease,” said Barry Baumel, MD, of the University of Miami Miller School of Medicine in Florida, and the trial’s principal researcher.

“These positive results, which includes improved patient reported outcomes, encourages us to continue to look at this approach to the treatment of this devastating degenerative brain disease,” Baumel added.

The levels of anti-inflammatory molecules (sIL-2R alpha, IL-4, IL-10 and IL-12) and markers of the formation of new blood vessels (VEGF, IL4, and IL-6) were increased significantly in patients treated with any dose of Lomecel-B compared to those on placebo.

A significant increase in the volume of the left hippocampus brain region — important for learning and memory processing — was seen in patients treated with high-dose Lomecel-B after 13 weeks of infusion versus those on placebo. The increase was transient, however, as by week 26 no difference was seen between the groups. Also, no difference was seen between the low-dose Lomecel-B and placebo groups.

“While preliminary, the MRI results are very promising in suggesting that Lomecel-B may reduce brain damage due to Alzheimer’s disease progression, and promote regenerative responses,” said Susan Bookheimer, PhD, of the UCLA School of Medicine, in California, and also a member of Longeveron’s Alzheimer’s Program Steering Committee.

A significant increase in the levels of D-dimer — a marker of vascular disease — was seen in the high-dose Lomecel-B group, but no increase was detected for the low-dose group. Also, in this group no differences were seen for neuronal-related biomarkers analyzed when compared to placebo.

Overall, the Phase 1 trial results “provide support for our hypothesis that Lomecel-B can potentially reduce Alzheimer’s disease associated brain inflammation, improve the function of blood vessels in the brain, reduce brain damage due to Alzheimer’s disease progression, and promote regenerative responses,” said Anthony Oliva, PhD, of Longeveron.

The trial results will be published soon in a peer-review journal and announced on the company’s website.