Australia-based Mesoblast Limited (ASX: MSB; Nasdaq: MESO) has submitted a Biologics License Application to the US FDA and requested modular review of the filing for rexlemestrocel-L (Revascor), targeting the prevention of life-threatening gastrointestinal bleeding caused by right ventricular dysfunction in end-stage heart failure patients implanted with a left ventricular assist device (LVAD). The submission represents the company's first BLA filing for rexlemestrocel-L and positions the asset as a potential first approved cellular therapy for LVAD-associated complications.
The filing seeks approval in a narrowly defined but high-mortality patient population: those with end-stage heart failure with reduced ejection fraction who have received an LVAD, a mechanical pump implanted in over 2,500 patients annually in the US, approximately 80% of whom undergo the procedure as permanent destination therapy. Gastrointestinal bleeding in this group arises from progressive right ventricular dysfunction. Rexlemestrocel-L holds both Orphan Drug Designation for prevention of life-threatening major mucosal bleeding events and Regenerative Medicine Advanced Therapy designation for this patient population, the company said, providing eligibility for rolling and priority reviews of the BLA. No PDUFA target action date has been disclosed, consistent with the early-stage modular submission process.
The clinical evidence package supporting the filing draws on two placebo-controlled randomized studies conducted in patients with chronic heart failure. The larger study enrolled 565 patients with New York Heart Association class II/III heart failure with reduced ejection fraction. A second, more directly relevant trial enrolled 159 end-stage heart failure patients implanted with an LVAD. The company has not publicly disclosed detailed efficacy outcomes from these studies in the context of the current BLA submission, and the modular review pathway means the FDA will assess data packages as they are submitted rather than reviewing a complete application simultaneously. The modular approach is particularly relevant here given the RMAT designation, which facilitates rolling review and allows early engagement with the agency on clinical and manufacturing data.
Rexlemestrocel-L is an allogeneic preparation of immunoselected and culture-expanded mesenchymal precursor cells. The therapy is designed to address systemic and cardiac inflammation that characterizes heart failure progression, releasing anti-inflammatory factors that modulate multiple effector arms of the immune system. In the LVAD setting, the proposed mechanism is that by reducing inflammatory burden and microvascular insufficiency — particularly in patients with ischemic cardiomyopathy, who represent the majority of LVAD destination therapy recipients — the therapy may attenuate the right ventricular dysfunction that drives gastrointestinal bleeding events. Patients with ischemic heart failure have a 76% lower likelihood of left ventricular functional recovery following LVAD implantation compared with non-ischemic patients, and face increased mortality over the initial one to two years, according to data cited by the company.
The filing comes as the FDA has issued recent draft guidances on demonstrating substantial evidence of effectiveness and on CMC considerations for cell and gene therapies, both of which are relevant to sponsors developing regenerative medicines.