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Longeveron Takes Aim at Aging with Cell Therapy

Investors did not like the recent news, but there is still reason for hope.


Longeveron has just announced the first data from its Phase 2b clinical trial that targets frailty with Lomecel-B, an MSC-based cell therapy.

A longevity strategy built in

More and more, biotech start-ups are applying longevity strategies to their therapeutic pipelines. Among them, Longeveron stands out as one of the few companies taking a cell-based approach. Relative to the more commonly employed strategy of using drugs, cell therapy is a more novel and interesting, although still unproven, technique. Drugs typically have well-defined mechanisms of action that do not change with time or environment. Their delivery, absorption, and removal from the body are also easy to measure and predict.

Cells, on the other hand, have an immeasurable number of behaviors that could impact pathology. They migrate, divide, differentiate, signal to other cells, degrade and build the extracellular matrix, and release inflammatory and anti-inflammatory cytokines. Cells are also not predictably metabolized by the liver like drugs are. Often, transplanted cells eventually die off, but it’s possible that they can also integrate with the recipient’s tissue and survive for years.

Perhaps most importantly, cells also respond to their environment. While a drug is still the same chemical compound whether it’s in a young, healthy kidney or surrounded by amyloid beta plaques in the brain, a cell’s behaviors will change dramatically. There are many cellular behaviors that may play a role, but the latest evidence is beginning to point to the secretion of bioactive molecules and direct cell-to-cell contact as the responsible mechanisms behind the therapeutic effects that have been seen in animal models.

Most cell therapies under development focus on a single disease and tissue, but Longeveron’s strategy targets the whole body. Its lead candidate, Lomecel-B, is a type of medicinal signaling cell (MSC) derived from the bone marrow of young, healthy donors. These cells have been shown to promote tissue repair and immune function, among other benefits. While autologous cells harvested from the patients themselves trigger less of an immune response, patient-derived cells may have the same defects of aging and disease that they are being used to treat. MSCs have been shown to provoke a minimal immune response, even when derived from a different donor. They can also be collected from young, healthy patients without much consequence to the donor.

A Phase 2b study for frailty

Frailty decreases quality of life, reduces the body’s ability to cope with stressors, and increases the risk of morbidity, mortality, and healthcare usage. It is also well accepted that frailty is a multi-organ condition and aging-related, making it a good target for anti-aging treatments in the absence of an approval pathway [1].

In this study, a single intravenous infusion of MSCs was given to patients at four different doses (25, 50, 100, and 200 million cells) along with a placebo, with approximately 30 patients per group. These patients were between the ages of 70-85, mildly to moderately frail, and had elevated TNF-a levels (an inflammatory cytokine). The primary endpoint was the distance that patients could walk in a six-minute walk test (6MWT) relative to baseline, 6 months after treatment.

The three highest doses all showed significant increases from baseline to 6 months, while the lowest dose and placebo groups did not. However, when adjusting for multiple comparisons, this statistical significance disappeared, although the highest dose was nearly significant at p = 0.0653. In this group, patients were able to walk an average of 49.3 meters further than their baseline, compared to the 8.0 meters further achieved by those receiving the placebo.

A secondary analysis of the primary endpoint was also conducted to determine if there was a dose-response relationship between Lomecel-B and 6MWT. The relationship was found to be statistically significant, with patients who received a higher dose of cells showing a greater improvement on the 6MWT. Further, patients who received either 50 or 200 million cells improved significantly at the exploratory time point of 9 months compared to placebo, even with the statistical correction.

Secondary endpoints included a patient-reported questionnaire on physical function (SF-20a) and TNF-a levels. The SF-20a showed no differences between placebo and any of the treatment arms and TNF-a levels are still being analyzed. Additionally, no serious adverse events related to Lomecel-B treatment were reported. Other, exploratory measures also have not yielded significant differences, including “assessments of physical function, sexual function, fear and risk of falling, depression, cognition, frailty status, pulmonary function, and clinical outcomes.”


Like many clinical trials, the results from this phase 2b study are ambiguous. Complicating this interpretation even further, this data has not yet been peer reviewed. We should be careful about drawing conclusions from data reported via press release prior to being published in a scientific journal.

Improvements in the 6MWT were seen at 9 months and in the dose-response analysis, but not for the 6 month, pre-determined primary endpoint. The highest dose also showed the highest efficacy, leaving open the possibility that even higher doses or perhaps multiple rounds of treatments could yield better outcomes. The treatment also continues to show good signs of safety. However, other secondary and exploratory measures did not improve like we might expect they would if the treatment were broadly impacting aging and frailty.

Investors did not respond favorably to the news, as Longeveron’s stock price fell by approximately 30%. While the market is not a particularly reliable interpreter of scientific data, it may hint at how Longeveron’s leadership will decide to move forward given these results. Geoff Green, the CEO of Lonveveron, stated that the company plans on reviewing the trial data with frailty experts and potentially regulatory bodies before committing to a future direction.

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[1] Chen, X., et al. Frailty syndrome: an overview. Clinical Interventions in Aging (2014).

About the author

Greg Gillispie

Greg is a recent graduate from the Wake Forest Institute for Regenerative Medicine. He strongly believes that age-related diseases have common underlying mechanisms at play and that an ounce of prevention is worth a pound of cure. In addition to writing for LEAF, Greg continues to conduct laboratory research in stem cell regeneration and cellular senescence. He is also an avid runner, curious reader, proud dog owner, and a board game enthusiast.
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