United States Food & Drug Administration (FDA) Supports Accelerated Approval Pathway for Rexlemestrocel-L in End-Stage Heart Failure Patients with a Left Ventricular Assist Device (LVAD)

NEW YORK, March 10, 2024 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced that U.S. FDA supports an accelerated approval pathway for rexlemestrocel-L, Mesoblast’s allogeneic mesenchymal precursor cell (MPC) product, in patients with end-stage ischemic heart failure with reduced ejection fraction (HFrEF) and a left ventricular assist device (LVAD). FDA provided this feedback in formal minutes to the company following the Type B meeting held with FDA on February 21, 2024 for rexlemestrocel-L (Revascor) under the existing Regenerative Medicine Advanced Therapy (RMAT) designation.

“We are very pleased with FDA’s feedback that the presented results from our pivotal study of rexlemestrocel-L in end-stage HFrEF patients with LVADs may support an accelerated approval,” said Mesoblast CEO Dr. Silviu Itescu. “We intend to request a pre-Biologics License Application (BLA) meeting to discuss data presentation, timing and FDA expectations for an accelerated approval filing.”

Every year in the United States over 100,000 patients progress to end-stage HFrEF. In these patients, more than 2,500 life prolonging LVADs are implanted in the US annually, of whom approximately 80% undergo the procedure as destination or permanent therapy.¹ Most patients receiving LVADs as destination therapy have an ischemic HFrEF etiology. Compared to patients with non-ischemic HFrEF, patients with ischemic HFrEF have a 76% lower likelihood of LV functional recovery following LVAD implantation,² and increased mortality over the initial 1-2 years.³ Resistance to functional recovery in ischemic HFrEF patients is thought to be due to excessive inflammation and microvascular insufficiency in the ischemic myocardium.⁴

In the placebo-controlled LVAD-MPC Study #2, 70 patients with end-stage ischemic HFrEF were randomized at the time of LVAD implantation surgery to either a single intervention with rexlemestrocel-L (150 million STRO3-immunoselected and culture-expanded allogeneic cells) or placebo injected directly into the left ventricular myocardium. Key findings were:

• Ischemic controls were characterized by persistently elevated levels of the inflammatory cytokine IL-6, by reduced ability to be weaned from LVAD support, and by high mortality.
• In contrast, in ischemic patients treated with rexlemestrocel-L, IL-6 levels returned to normal by 2 months and remained low through 12 months.
• 63% of ischemic patients who received a single administration of rexlemestrocel-L successfully underwent temporary weaning from full LVAD support as early as month 2 as compared with 36% of controls (p = 0.008).
• The cumulative incidence of successful temporary weans off the LVAD device over 6 months was also increased by 1.55-fold over control in ischemic patients who received rexlemestrocel-L ([95% CI 1.01, 2.36]; p=0.02).
• Only 4.9% of ischemic patients treated with a single administration of rexlemestrocel-L died from month 2 through month 12, as compared with 26.9% of ischemic controls, an 82% reduction (p = 0.02).