Mesoblast has received an FDA BLA filing number for rexlemestrocel-L and requested a modular review to prevent life-threatening gastrointestinal bleeding in LVAD patients with end-stage heart failure.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
Mesoblast has received a Biologics License Application (BLA) filing number from the U.S. Food and Drug Administration (FDA) for rexlemestrocel-L, marking the start of the regulatory review process for the investigational allogeneic cell therapy. The company has also requested a modular review of its BLA for preventing life-threatening gastrointestinal (GI) bleeding caused by right ventricular dysfunction in patients with end-stage heart failure who require a left ventricular assist device (LVAD).
The therapy has already received both Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations from the FDA for this indication, enabling eligibility for rolling submissions and potential priority review.
Cell Therapy Targets Inflammation Driving Advanced Heart Failure Complications
Rexlemestrocel-L is an allogeneic therapy made from immunoselected, culture-expanded mesenchymal precursor cells (MPCs), a specialized stem cell population that helps regulate excessive inflammation. The investigational therapy is intended to reduce the inflammatory processes that contribute to disease progression across the spectrum of heart failure with reduced ejection fraction (HFrEF), including patients with advanced disease supported by mechanical circulatory devices.
In patients with LVADs, persistent inflammation and progressive right ventricular dysfunction substantially increase the risk of severe gastrointestinal bleeding, a major complication associated with hospitalization, morbidity, and mortality. Currently, no approved therapy specifically prevents these bleeding events.
Clinical Development Supports Regulatory Submission
The BLA is supported by clinical evidence generated from two randomized, placebo-controlled studies evaluating rexlemestrocel-L in chronic heart failure.
The development program included a 565-patient trial (NCT02032004) involving patients with New York Heart Association (NYHA) Class II/III HFrEF and a 159-patient study in patients with end-stage HFrEF receiving LVAD support (NCT02362646). These studies established the clinical evidence supporting the regulatory submission and evaluated the therapy across different stages of advanced heart failure.
The current BLA specifically focuses on preventing life-threatening major mucosal gastrointestinal bleeding in the LVAD population, where right ventricular dysfunction remains a significant unmet clinical challenge.
Regulatory Environment May Support Rare Disease Cell Therapies
The submission comes as the FDA signals greater regulatory flexibility for therapies targeting rare, serious diseases. Recent draft guidance on demonstrating substantial evidence of effectiveness and updated recommendations on chemistry, manufacturing, and controls (CMC) for cell and gene therapies reinforce the agency’s willingness to consider flexible development pathways for products addressing conditions with high mortality and irreversible morbidity.
These policies may benefit advanced regenerative therapies such as rexlemestrocel-L, particularly in orphan indications with limited therapeutic alternatives.
Leadership Highlights Urgent Unmet Need
Chief Executive Dr. Silviu Itescu said Mesoblast looks forward to working closely with the FDA to bring rexlemestrocel-L to patients with end-stage heart failure who rely on mechanical circulatory support and face a high risk of life-threatening gastrointestinal bleeding resulting from progressive right heart failure.
Growing Clinical Need in Advanced Heart Failure
Chronic heart failure affects approximately 6.5 million people in the United States and an estimated 26 million people worldwide. Disease progression remains associated with substantial mortality despite recent advances in guideline-directed therapies.
More than 100,000 U.S. patients progress to end-stage HFrEF each year, while over 2,500 LVADs are implanted annually, with most serving as permanent destination therapy. Patients with ischemic heart failure often experience poorer recovery following LVAD implantation because persistent inflammation and impaired myocardial microvascular function continue to drive adverse outcomes.
If accepted for full review, rexlemestrocel-L could become the first cell therapy specifically approved to prevent life-threatening gastrointestinal bleeding in patients with LVAD-supported end-stage heart failure, expanding treatment options for a population with few effective preventive therapies.
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About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.