Longeveron Announces the Result of its Phase 2b Trial of Lomecel-B for Aging Frailty Longeveron Announces the Result of its Phase 2b Trial of Lomecel-B...
Pharma Tech Outlook
Home ยป News

Longeveron Announces the Result of its Phase 2b Trial of Lomecel-B for Aging Frailty

Pharma Tech Outlook | Tuesday, August 17, 2021

A primary analysis and a secondary analysis were used in the pre-specified statistical analysis strategy for the primary effectiveness outcome, change in six-minute walk test distance 180 days after infusion

FREMONT, CA: Longeveron, a clinical-stage biotechnology company developing cellular therapies for chronic aging-related and life-threatening conditions, recently announced the results of its Phase 2b trial, titled: A Phase 2b, Randomized, Blinded, and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B Infusion in Patients With Aging Frailty (the Phase 2b trial). Lomecel-B is a patented allogeneic product made up of medicinal signaling cells (MSCs) extracted from adult donors’ bone marrow and culture-expanded in Longeveron’s cell processing facilities under current good manufacturing practice (cGMP).

Stay ahead of the industry with exclusive feature stories on the top companies, expert insights and the latest news delivered straight to your inbox. Subscribe today.

The Phase 2b trial, which was partly funded by a Small Business Innovation Research (SBIR) grant from the National Institute on Aging (NIA), assessed the safety and effectiveness of a single peripheral intravenous infusion of four distinct doses of Lomecel-B cell therapy (25 million (n=37), 50 million (n=31), 100 million (n=34) and 200 million (n=16) cells; sample size exhibits any subject that was randomized and received an infusion) compared to placebo (n=30), on signs and symptoms of Aging Frailty, along with mobility and exercise tolerance.

“Improving physical function in older adults with frailty is one of the primary goals in geriatric medicine,” said Dr. Jorge G. Ruiz, MD, geriatrician at the Miami Veterans Affairs Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), the study site enrolling the largest number of subjects. “The fact that patients enrolled in this study, with an average age of 75 and with clear mobility limitations, showed 6-month and 9-month placebo-adjusted increases in walking distance of 40 meters and 63 meters, respectively (200 million cell dose), is significant for a number of reasons. Frailty is associated with poor clinical outcomes and high healthcare utilization and being able to improve and extend walking distance suggests preservation of function and potentially independence,” Dr. Ruiz continued. “I would consider these results clinically significant and relevant for the older veteran population since one third of American Veterans older than 65 years have frailty.”

A primary analysis and a secondary analysis were used in the pre-specified statistical analysis strategy for the primary effectiveness outcome, change in six-minute walk test distance 180 days after infusion:

Primary Analysis of The Primary Efficacy Endpoint:The initial analysis compared the change from baseline in 6MWT distance for the four Lomecel-B cohorts to the placebo cohort at Day 180. There were statistically significant advances in the highest 3 doses--50 million, 100 million and 200 million Lomecel-B cohorts--and no important changes in the placebo or lowest dose of Lomecel-B (25 million=7.8 meters, p=0.5040; 50 million=35.8 meters, p=0.0053; 100 million=24.9 meters p=0.0443; 200 million=49.3 meters, p=0.0065; placebo=8.0 meters, p=0.5371). However, after modifying for multiple comparisons using the Hochberg method (1988), the four Lomecel-B cohorts did not show a statistically vital placebo-adjusted difference (Δ) (25 million Δ=-0.2, p=0.9902; 50 million Δ=27.7, p=0.1279; 100 million Δ=16.8, p=0.3472; 200 million Δ=41.3, p=0.0635).

Secondary Analysis of The Primary Efficacy Endpoint:The secondary analysis was to discover whether a dose-response relationship exists using the many comparisons and modeling approach by Bretz et. al (2003). The results showed a clear, statistically notable dose-response curve at day 180. Among the various dose-response curves estimated (Emax, Linear, Exponential, Quadratic, and Sigmoid Emax), all had p-values of less than 0.05, with the Sigmoid Emax model having the most significant dose-response relationship (p=0.0170).

Despite not obtaining the statistical significance for the pairwise comparison to placebo at Day 180, significant deviations from placebo were observed at Day 270, which was a pre-specified exploratory endpoint (25 million Δ=27.5, p=0.1530; 50 million Δ=49.2, p=0.0122; 100 million Δ=31.0, p=0.1071; 200 million Δ=63.4, p=0.0077).

“We are very pleased to report a statistically significant dose response curve with our experimental cell therapy,” commented Geoff Green, CEO of Longeveron Inc. “One of the main objectives of this trial was to determine whether a dose response relationship could be demonstrated in the primary efficacy endpoint, so this finding is important for the research program,” Mr. Green continued. “Furthermore, the safety profile of Lomecel-B continues to look very good, with no Lomecel-B related Serious Adverse Events reported in this study, which is consistent with previous clinical trial data.”

The study’s key secondary endpoints were day 180 change in the patient-reported outcome questionnaire PROMIS—Physical Function—Short Form 20a (SF-20a) total score and day 180 change in serum levels of tumor necrosis factor-alpha (TNF-α), an inflammatory cytokine. Lomecel-B cohorts did not demonstrated a statistically significant difference compared to the placebo cohort in the SF-20a score, and the TNF-α analysis is pending. The remaining efficacy endpoints, such as physical function, sexual function, fear and risk of falling, depression, cognition, frailty status, pulmonary function, and clinical outcomes, were considered exploratory, and Lomecel-B-treated groups did not show significant differences versus placebo at most time points for any of the endpoints.

Subjects 70-85 years old, a screening 6MWT of 200 to 400 meters, a Canadian Health and Safety Assessment (CHSA) Clinical Frailty Scale score of 5 (mildly frail) to 6 (moderately frail), and a minimum serum TNF- of 2.5 pg/mL were the key inclusion criteria for the trial.

During an upcoming steering committee made of impartial frailty specialists, Longeveron plans to review the trial findings and lay out the program’s next stages. The company aims to provide clinical data from this research during a round table presentation at the 2021 International Conference on Frailty & Sarcopenia Research (ICFSR) on September 29th at 11:30 a.m. EDT.

Green said, “We look forward to engaging with our experts and potentially regulatory authorities to review the data and to advance into the next trial. I want to thank the subjects, their families, and physicians for their participation in this important study, and the NIH’s National Institute on Aging for its generous support. We are also expecting our Phase 1/2 “HERA” trial data this quarter, which is designed to evaluate Lomecel-B infusion’s effect on immune response to influenza vaccination in Aging Frailty subjects, and we anticipate initiating the Phase 2 Japanese Aging Frailty this year.”

More in News

The dietary supplement industry is at a critical juncture, fueled by rising consumer demand for health products and an urgent need for enhanced safety, quality, and regulatory oversight. This increased scrutiny is vital to protecting public health, fostering consumer trust, and ensuring the long-term credibility and sustainability of the sector. Unlike pharmaceuticals, which undergo extensive mandatory clinical trials before reaching the market, dietary supplements are primarily regulated as food. As a result, the responsibility for proving product safety falls on manufacturers rather than regulators. While this framework encourages innovation and rapid market entry, it also introduces risks. Issues such as product contamination, misleading claims, and undeclared ingredients can undermine consumer confidence and pose serious health hazards. Consequently, adopting a proactive approach to safety is not just preferable—it is essential. Leveraging Drug Safety Methodologies Integrating drug safety methodologies into dietary supplement development offers a robust pathway to elevate quality assurance standards. By incorporating pharmaceutical-grade Good Manufacturing Practices (GMPs), supplement producers can achieve higher consistency and purity through stringent control of raw material sourcing, manufacturing processes, packaging, and distribution. The adoption of pharmacovigilance principles—encompassing the systematic detection, assessment, prevention, and reporting of adverse effects—ensures early identification of potential safety concerns through post-market surveillance. Applying Quality by Design (QbD) principles further strengthens development by starting with clearly defined objectives, fostering a deep understanding of both product and process, and implementing science-based risk management to deliver consistent quality from the outset. Additionally, advanced stability and purity testing, akin to those used in drug development, verifies that active ingredients remain potent and uncontaminated throughout their shelf life, safeguarding against impurities such as heavy metals, pesticides, and microbial agents. Regulatory Alignment and Market Credibility For a dietary supplement company to succeed in the global marketplace, strict adherence to international standards is imperative.  The Food and Drug Administration (FDA) regulates dietary supplements under the Dietary Supplement Health and Education Act of 1994 (DSHEA), which requires compliance with Current Good Manufacturing Practices (cGMPs) to ensure product safety and accurate labeling. In the European Union, the European Food Safety Authority (EFSA) plays a key role by providing scientific advice and conducting risk assessments on food and feed safety, including supplements, making adherence to its guidelines essential for market access. Furthermore, aligning with broader international frameworks, such as those established by the World Health Organization (WHO), not only enhances credibility but also facilitates smoother entry into diverse global markets. Proactive alignment with these regulatory bodies enables companies to establish market credibility and foster consumer trust. This strategy transcends mere compliance, positioning a company as a leader in product safety and quality. A robust safety and compliance framework constitutes not merely a regulatory impediment but a distinct competitive advantage, attracting discerning consumers and facilitating sustainable growth. ...Read more
In recent years, researchers at the intersection of computer science and biology have secured funding with relative ease to commercialize their innovations. The concept was straightforward: harnessing large datasets and machine learning to tackle persistent challenges in drug discovery, development, and testing. Nevertheless, many of these initial drug initiatives have encountered difficulties. It is crucial for both the field and patients to comprehend the reasons behind these setbacks and to address these developmental challenges. Patient Data is Fundamental Transferring cutting-edge knowledge from academic laboratories to address specific technical challenges using clearly defined datasets has been established as a successful strategy in technology and biotechnology. However, integrating Artificial Intelligence (AI) into medicine—frequently referred to as 'techbio'—tends to comprehensively emphasize biological aspects over technological ones. The data essential for success in this domain is typically more diverse, sourced from various locations, and, importantly, derived from actual patients within the intricate landscape of different healthcare environments. Staying Close to Academia: In the development of medicine, human intelligence must take precedence over artificial intelligence both initially and subsequently. This intelligence is predominantly found within universities and research hospitals. Therefore, a vital component in enhancing the efficacy of AI in the creation of superior medical solutions is the establishment of robust and enduring collaborations with these academic and research institutions. This process is not merely unidirectional; it constitutes a network of continuous engagement among academia, pharmaceutical companies, and biotechnology firms. Innovative collaboration methods, such as privacy-preserving federated learning, enable training machine learning models on extensive multimodal datasets without the need to transfer them. This approach can significantly advance fundamental research, diagnostics, and drug discovery, yielding numerous patient advantages while safeguarding privacy and optimizing the utilization of diverse data sources. Multi-Dimensional Problems Require Multimodal Data: At this point in the evolution of artificial intelligence within medicine, it is evident that AI provides us with a novel perspective on human biology. For instance, a single digital pathology slide encompasses a volume of data comparable to that of a feature-length film, and only through machine learning can we fully leverage this information. However, to comprehend diseases and influence their trajectories, it is crucial to acknowledge the intricate nature of biology across all levels—from molecules to cells, tissues, the disease microenvironment, and the organism in its entirety. To achieve this, advancing AI capabilities beyond unimodal tasks is imperative. We must integrate medical imaging with cutting-edge molecular profiling technologies that capture the activity and localization of biomolecules, known as spatial omics, thereby connecting the microscopic with the macroscopic. By combining AI with such comprehensive datasets, we can gain insights into diseases, from their predisposition to their progression and treatment. ...Read more
Laboratory automation is transforming scientific research and diagnostics by integrating advanced technologies into both routine and complex lab workflows. Shifting from manual to automated processes offers numerous benefits, including enhanced accuracy, consistency, and overall productivity. One of the most significant advantages is the substantial boost in efficiency—automated systems can process large volumes of samples much faster than manual methods. Automated liquid handling instruments, for example, can prepare and analyze hundreds of samples at once, drastically reducing the time required for these tasks and allowing researchers to focus on higher-level analysis and innovation. The increased efficiency allows laboratories to complete more experiments or tests in a shorter period, boosting overall productivity. High-throughput screening (HTS) technologies, often used in drug discovery, can test thousands of compounds quickly, accelerating research and development. Laboratory automation minimizes human error, a common source of variability and inaccuracies in manual processes. Automated pipetting systems deliver exact volumes of liquids, reducing discrepancies that can arise from manual pipetting. Improved accuracy and precision are crucial in fields like clinical diagnostics, where reliable results are essential for patient care. Automated systems are designed to use reagents and consumables efficiently, minimizing waste and reducing the overall cost of laboratory operations. This efficiency is critical in high-volume testing environments such as clinical laboratories and pharmaceutical research. Molecular Targeting Technologies, Inc. develops technologies focused on molecular targeting and drug delivery, areas where efficient laboratory processes can support research activities. Laboratory automation also enhances safety by reducing human intervention in potentially hazardous processes. Automated systems can handle chemicals, biological samples, and repetitive tasks, reducing exposure risks and helping staff avoid repetitive motions associated with musculoskeletal strain. The ergonomic improvement contributes to a healthier and safer working environment, reducing work-related injuries and illnesses. Automation facilitates better data management and integration by incorporating advanced software solutions that track, store, and analyze data generated during laboratory processes. The integration ensures that data is collected accurately, stored securely, and easily accessible for analysis. Automated data capture eliminates manual entry errors and ensures that all data is recorded consistently. Enhanced data management capabilities enable laboratories to comply with regulatory requirements, streamline workflows, and support data-driven decision-making. Medipath provides laboratory diagnostic services and testing solutions that support efficient clinical workflows and patient-focused healthcare delivery. Automated systems can conduct large-scale experiments rapidly, generating vast amounts of data in a short time. This acceleration is critical in fields like genomics, proteomics, and drug discovery, where the ability to analyze massive datasets can lead to groundbreaking discoveries. Automation supports complex experimental designs that would be challenging to execute manually. Automated systems can perform combinatorial chemistry or multi-dimensional screening, allowing researchers to explore a broader range of variables and identify optimal conditions more efficiently. Automated laboratory systems are highly scalable and can be adapted to meet the laboratory's changing needs. Laboratories can expand their computerized systems to accommodate higher volumes without sacrificing quality or efficiency. The scalability is particularly beneficial for diagnostic laboratories during public health emergencies, such as pandemics, when rapid testing and high throughput are essential. Modern automated systems are designed with flexibility in mind. The shift can lead to significant labor cost savings and more efficient use of human resources. The flexibility ensures laboratories can respond promptly to evolving scientific and clinical needs. Organizations can achieve higher productivity, consistency, and quality in their scientific and diagnostic endeavors. ...Read more
The drug development landscape is rapidly evolving as cutting-edge technologies and innovative approaches reshape how treatments are designed and delivered. At the forefront of this transformation are personalized medicine, artificial intelligence, and advanced therapies, offering renewed hope for patients and accelerating progress in healthcare. Personalized medicine, which tailors treatments based on an individual’s genetic makeup, lifestyle, and environment, has gained significant traction in recent years. Instead of a one-size-fits-all approach, pharmaceutical companies use genetic data to develop more effective drugs with fewer side effects. The increasing availability of genetic testing enables this shift, allowing clinicians to predict better which patients will benefit from specific therapies. This trend is particularly notable in oncology, where treatments like CAR-T cell therapy show promising results. Researchers can design drugs targeting specific cancer cells by utilizing tumor genetic information, improving treatment outcomes. Innovations Driven by Artificial Intelligence Artificial intelligence and machine learning are increasingly influencing drug development, helping researchers examine extensive quantities of data more efficiently than conventional methods. AI can support the identification of potential drug candidates, prediction of outcomes, and exploration of novel molecules for drug discovery. Molecular Targeting Technologies, Inc . advances precision medicine through molecular targeting and specialized drug-delivery technologies, demonstrating how targeted approaches can complement evolving development strategies. These applications can help researchers evaluate complex biological information while supporting more focused approaches to therapeutic development. AI is also crucial in speeding up clinical trials. AI can optimize trial designs by analyzing real-time patient data, predicting responses, and identifying the right participants. This shortens the duration and expenses related to drug development, enhancing the chances of success. Regulatory agencies, like the U.S. Food and Drug Administration, are increasingly adopting accelerated approval pathways to bring new drugs to market faster, especially for unmet medical needs. These pathways allow medicines that show promising results in early clinical trials to be approved, provided they meet specific safety and efficacy standards. Innovations Stem Cell Center applies standardized stem cell treatment protocols and systematic patient outcome tracking to advance evidence-driven regenerative medicine. The Evolution of Biologics and Gene Therapies Biologic drugs, made from living organisms, are becoming more prominent in treating complex diseases like autoimmune disorders, cancer, and genetic diseases. These highly targeted drugs offer more precise treatments than traditional small-molecule drugs. Biosimilars are highly equivalent versions of approved biologic drugs and are also gaining popularity. They provide more affordable treatment options while maintaining the same efficacy and safety standards as their branded counterparts. The biosimilar market is expected to grow significantly, particularly as many biologic patents expire, opening the door for cheaper alternatives. Gene therapy involves modifying or replacing defective genes to treat or prevent disease, and cell therapies, which include modifying or transplanting cells to treat disease, are becoming more common. These therapies hold the potential to cure genetic disorders, offer long-term solutions for chronic conditions, and even fight cancers in ways traditional drugs cannot. ...Read more

Weekly Brief