Phase III trial of Revascor shows safety and efficacy in chronic low back pain.- Mesoblast

Mesoblast announced results from the Phase III randomized controlled trial of its allogeneic mesenchymal precursor cell (MPC) therapy Revascor (rexlemestrocel-L) in 404 enrolled patients with chronic low back pain (CLBP) due to degenerative disc disease (DDD) refractory to conventional treatments. The results indicate that a single injection of rexlemestrocel-L may provide a safe, durable, and effective opioid-sparing therapy for patients with chronic inflammatory back pain due to degenerative disc disease, and that greatest benefits are seen when administered earlier in the disease process before irreversible fibrosis of the intervertebral disc has occurred. Patients were randomized 1:1:1 to receive a single intra-discal injection of either rexlemestrocel-L using a unit dose of 6 million allogeneic mesenchymal precursor cells (MPCs), with or without hyaluronic acid (HA) carrier, or saline control, and stratified for opioid use at baseline to ensure all three treatment arms were equally represented in this pre-defined population. The effectiveness of rexlemestrocel-L alone or rexlemestrocel-L + HA through 24 months was evaluated on reduction in pain using Visual Analog Score (VAS) and on disability or function using two measurements, Oswestry Disability Index (ODI) and EuroQoL 5-Dimensional (EQ-5D) Index. In addition to assessing the durability of pain reduction with rexlemestrocel-L treatment, this study evaluated primary outcomes using composite measures of pain reduction together with functional responses to treatment, as well as exploratory composites of pain reduction and functional responses in the context of opioid reduction. A single injection of MPC + Hyaluronic Acid (HA) carrier resulted in: Achievement of significant and durable reductions in CLBP through 24 months across the entire evaluable study population (n=391) compared with saline controls. Greatest pain reduction observed in the pre-specified population with CLBP of shorter duration than the study median of 68 months (n=194), significantly greater reduction at all time points (1, 3, 6, 12, 18 and 24 months) compared with saline controls. Significantly greater pain reduction in the pre-specified patient subset of opioid users (n=168) at all time-points compared with saline controls. Confirmation of durable pain reduction seen with the combination of rexlemestrocel-L + HA in the previous randomized controlled trial, where HA control alone was not significantly different from saline. Increased composite outcomes of reduction in pain together with improvement in function in those with CLBP of shorter duration than 68 months, the median for the study; however, the composite outcomes of pain and function did not reach statistical significance across the entire study. No safety concerns over the 24-month period of follow-up in the entire study population. Importantly, in patients using opioids at baseline, the results showed: Significant reduction in opioid use over 24 months in patients treated with MPC + HA, while increased opioid use occurred in saline controls. In addition, treatment with MPC + HA resulted in nearly four times more opioid users achieving 50% reduction in pain as well as reduction in opioid use by 24 months than those treated with saline. Across the entire treated population in the Phase III trial (n=391 evaluable at follow-up), patients who received a single injection of MPC + HA had a significantly greater reduction in pain at both 12 and 24 months compared with saline controls as measured by VAS on a scale of 1-100. Data shows the least-squared (LS) mean change from baseline in patients treated with MPC + HA was -27.6 at 12 months and -26.0 at 24 months from a baseline mean VAS of 60.4 (p=0.014 and p=0.036, respectively, compared with saline-treated controls). Patients who received MPCs alone had mean VAS reductions intermediate between saline and MPC + HA, indicating an additive role for HA carrier, likely by increasing targeting of mesenchymal stromal cells to inflammatory sites. The durable pain reductions observed over 24 months confirm outcomes from a prior randomized controlled trial which showed that the same dose and formulation of MPC + HA resulted in significantly greater reduction in pain, as measured by LS mean change in VAS from baseline, at both 12 months and 24 months compared with saline (p=0.018 and p=0.006, respectively), whereas HA alone was not significantly different from saline. Maximal pain reduction with MPC + HA was seen in the pre-specified subset of patients treated within a shorter duration of CLBP than the study’s median of 68 months (n=194). Further, minimal to no pain (VAS < 20) was seen in 60% of these patients treated with MPC + HA at 12 months and in 54% at 24 months (p=0.011 and p=0.036, respectively, compared to saline controls).Mesoblast will meet with the FDA to discuss the results from this trial together with the earlier randomized controlled trial of MPC + HA, and potential approval pathways for rexlemestrocel-L + HA as treatment for durable reduction in CLBP due to DDD with opioid sparing activity.