Mesoblast Limited, an Australian company, has announced that a single intravenous (IV) infusion of its proprietary allogeneic mesenchymal precursor cell (MPC) product candidate MPC-300-IV was well tolerated and demonstrated dose-related improvements in clinical symptoms, physical function, and disease activity compared with placebo through the 12-week primary endpoint in a phase 2 clinical trial involving patients with biologic-refractory rheumatoid arthritis (RA).
The study recruited 48 patients with active RA who were receiving a stable regimen of methotrexate and who had shown an inadequate clinical response to at least one anti-tumor necrosis factor (TNF) agent. Of the 48 patients, 30 (63%) had received one or two biologic agents. The patients were randomly assigned to receive a single IV infusion of one million MPCs/kg (1 M/kg; n = 16); two million MPCs/kg (2 M/kg; n = 16); or placebo (n = 16). The study consisted of a 12-week primary study period with a 40-week follow-up period, for a total duration of 52 weeks.
The trial’s primary objective was to evaluate the safety and tolerability of a single IV MPC infusion in these biologic-refractory RA patients through 12 weeks of treatment. Additional objectives included evaluating clinical efficacy at the primary 12-week endpoint and assessing the durability of effects and the treatment’s safety profile through the full 52-week study.
There were dose-related improvements in many of the individual components of the American College of Rheumatology (ACR) composite after MPC treatment. The 2-M/kg group who had previously received one or two biologics showed a significant improvement compared with placebo in each of the following categories: swollen joint counts, the investigator’s global assessment, the patient’s global assessment, and pain scores.
ACR70 responses (at least a 70% improvement in the number of tender and swollen joints, and at least a 70% improvement in various clinical assessments) showed a dose-related effect after a single MPC infusion, with the greatest effect seen in the 2-M/kg group who had previously received one or two biologics compared with placebo (36% versus 0%, respectively). ACR50 responses showed a dose-related effect after a single MPC infusion, with the greatest effect seen in the 2-M/kg group who had previously received one or two biologics compared with placebo (55% versus 11%). ACR20 responses were greater in both the 2-M/kg and 1-M/kg groups who had received one or two biologics than in the placebo group (55% and 60% versus 33%).
MPC-300-IV consists of two million immunoselected and culture-expanded MPCs per kilogram, which are delivered intravenously. Current biologic therapies target individual cytokine pathways thought to be involved in the pathogenesis of RA, including TNF-alpha, interleukin (IL)-6, or IL-17, but not concomitantly. According to Mesoblast, there are at least two mechanisms of action by which MPC-300-IV may affect clinical RA outcomes through the concomitant inhibition of multiple cytokine networks:
Source: Mesoblast; August 8, 2016.