Longeveron CEO: Lomecel-B simultaneously targets multiple aging-related processes in Alzheimer’s, age-related frailty and beyond.
Hot on the heels of receiving the FDA’s coveted Regenerative Medicine Advanced Therapy (RMAT) designation for its Lomecel-B product, Longeveron this week revealed its lead cell therapy has also been granted Fast Track designation for the treatment of mild Alzheimer’s. The Miami-based biotech has now received five different FDA designations for Lomecel-B, and this latest one should help streamline its development and expedite its review as a potential Alzheimer’s therapy.
The Fast Track designation comes on the back of compelling Phase 2 trial results, which demonstrated that Lomecel-B slowed or prevented the progression of Alzheimer’s in some groups of patients with the mild form of the disease. Longeveron’s aim is now to move the therapy into the next phase of trials in Alzheimer’s as soon as possible, potentially as early as next year. But the company is not putting all its eggs in one basket…
Longevity.Technology: Derived from the bone marrow of young, healthy adult donors, Lomecel-B, a so-called “living cell product,” has demonstrated pro-vascular, pro-regenerative and anti-inflammatory effects. With multiple mechanisms of action, the drug is being explored for its potential in several indications, spanning neurodegeneration, frailty and heart conditions. Could we be looking at a ‘longevity drug’ in the making? To learn more, we caught up with Longeveron CEO, Wa’el Hashad.
Longeveron was founded with a mission to target age-related diseases, which are often characterized by chronic inflammation, combined with a decline in immune system and blood vessel function. The company’s approach involves building therapeutics, like Lomecel-B, from special living cells called medicinal signaling cells (MSCs) derived from donated bone marrow tissue.
Longeveron’s cell therapy manufacturing site in Miami, Florida.
One of the key mechanisms through which MSCs exert their therapeutic benefits is by releasing exosomes, growth factors and other proteins, such as anti-inflammatory cytokines, which have the potential to significantly reduce inflammation, while stimulating the promotion of regenerative and repair responses. This is why, rather than targeting amyloid plaques or neurofibrillary tangles, Longeveron is going after the inflammation of the central nervous system that is increasingly recognized as a driver of neurodegeneration in Alzheimer’s.
Multiple mechanisms of action
With preliminary clinical data showing that Lomecel-B simultaneously targets multiple aging-related processes, Hashad explains that an important part of the recent Phase 2 Alzheimer’s trial was demonstrating these effects in humans.
“We wanted to see if there was any data supporting the hypothesis of the mechanism of action, which is the anti-inflammatory and pro-vascular effect of the drug,” he says. “So, in addition to other clinical scales that you typically use in Alzheimer’s trials, we also added MRI measurement of brain volumes, which is a very objective exploratory endpoint.”
This means that, in addition to study results showing that Lomecel-B was safe, well-tolerated, and demonstrated statistically significant improvements in specified cognitive function measurements in certain groups, Longeveron also generated some compelling MRI data.
“We got a big, positive surprise from the effect that we saw on the MRI, which indicated that there was less shrinkage in the brain compared to placebo,” says Hashad. “And that was significant, not just on the total volume of the brain, but also on the hippocampal volume, which is the memory formation center of the brain.”
This data, Hashad believes, was instrumental in the company receiving the recent designations from the FDA, which should help accelerate the process to move Lomecel-B forward as a potential treatment for mild Alzheimer’s.
Recent FDA guidance for Alzheimer’s disease indicates that “clinical trials showing an effect on a surrogate endpoint that is determined to be reasonably likely to predict clinical benefit can be the basis for accelerated approval.” The MRI data from the Phase 2 trial, which can be considered a surrogate endpoint, may significantly expedite the development and approval process for Lomecel-B.
“We can now have a much more active dialogue with the FDA, and potentially discuss the possibility of an accelerated approach to bring the product to the market using surrogate endpoints, for example,” he says. “The next step is to meet with the FDA before the end of the year to talk about the blueprint for the next phase of development.”
Applications beyond Alzheimer’s
With chronic inflammation also heavily implicated in many other age-related conditions, Longeveron believes that the anti-inflammatory, pro-vascular mechanism of Lomecel-B can also play a role beyond the brain.
“We have an indication that Lomecel-B may work by reducing levels of inflammation, and also improving the health of the vascular system and therefore the blood supply and the blood flow to the brain and other areas of the body,” says Hashad.
In addition to its program in Alzheimer’s, Lomecel-B is also being explored as a treatment for age-related frailty, as well as a congenital heart condition called hypoplastic left heart syndrome (HLHS).
Age-related frailty, or sarcopenia, is thought to affect around 15% of individuals aged 65 and older, and significantly heightens the risk of adverse clinical outcomes from disease and injury. Despite its prevalence, no medical treatments for the condition have been approved by the FDA or any other regulatory body.
Longeveron has commenced multiple clinical trials of Lomecel-B in frailty but has faced some challenges in terms of determining the endpoints needed to demonstrate efficacy to the FDA.
“We have seen good data in our studies, but there is no product approved for aging related frailty, and we’re still trying to get an agreement with the FDA on what that indication is,” says Hashad. “So far, what we have used in our trials is the ‘six-minute walk test,’ which evaluates the distance a patient can walk within six-minutes. We have seen a statistically significant improvement in our Phase 2 study with this metric at nine months. We will continue to work with the FDA which also wants to see a more objective assessment as well, so we’re trying to get alignment on that before we proceed forward on that program.”
From cardiology to longevity?
Longeveron’s more recent work in cardiology is of keen interest to the company’s founder, the renowned cardiologist Dr Joshua Hare. While the program is currently focused on a rare, inherited condition, Hashad admits that the company is exploring the potential to target other heart-related indications.
“There are certain things that we’re working on that I cannot disclose at this time,” he says. “But cardiology remains one of Josh’s biggest passions, and we believe that Lomecel-B may have multiple potential applications within the heart disease area – as well as other products that we’re also working on.”
So, if Lomecel-B goes on to prove successful in multiple age-related diseases, would that make it a potential longevity drug? Hashad doesn’t bite, although he does believe the therapy could have more applications in other diseases.
“As a startup, we must focus on the work that we currently have at hand, but hopefully, as we continue to advance our work and grow, then we can embark on other areas of disease that can also benefit patients in the future,” he says. “There is no doubt that life expectancy is increasing around the world – the question is how we ensure that people are not just living longer but living longer with a better quality of life, whether by improving their heart health, muscle health, or brain health. We believe that Lomecel-B, and the other products that we’re working on in our labs, can potentially help to improve that quality of life.”
Photographs courtesy of Longeveron
