Mesoblast’s MPC: Positive Results

It’s hard to treat biologic refractory rheumatoid arthritis (RA). But now, with the results coming out of Mesoblast Limited, it may be a bit easier. The company is reporting that just one intravenous infusion of its allogeneic mesenchymal precursor cell (MPC) product candidate, MPC-300-IV, has resulted in some clinical success.

Allan Gibofsky, M.D., Professor of Medicine and Public Health at Weill Cornell Medical College and Attending Rheumatologist at Hospital for Special Surgery in New York, commented in the August 8, 2016 news release, “The safety and efficacy results of this study are very encouraging and suggest that Mesoblast’s cell therapy has the potential to fill the major unmet medical need of the biologic refractory RA population, where agents that provide consistent durable effects without the risk of opportunistic infections or malignancies are sorely needed.”

Included in the trial were 48 patients with active RA who were on a stable regimen of methotrexate and had an inadequate prior clinical response to at least one anti-tumor necrosis factor (TNF) agent. Patients received either a single intravenous infusion of 1 million MPCs/kg, 2 million MPCs/kg, or placebo.

As indicated in the news release, “Cell infusions were well tolerated with no infusion-related adverse events. There were no serious adverse events, and the safety profile over 12 weeks was comparable among placebo and MPC treatment groups….There was a dose-related improvement in many of the individual components of the ACR [American College of Rheumatology] composite following MPC treatment; the 2M/kg group who had previously received 1-2 biologics showed significant improvement over placebo in each of the following categories: swollen joint counts, investigator global assessment, patient global assessment, and patient pain scores. ACR70 responses overall showed a dose-related effect after a single MPC infusion, with the greatest effect seen in the 2M/kg group who had previously received 1-2 biologics…ACR50 responses overall showed a dose-related effect after a single MPC infusion, with the greatest effect seen in the 2M/kg group who had previously received 1-2 biologics…ACR20 responses were greater in both the 2M/kg and 1M/kg group who had previously received 1-2 biologics than placebo…

“A single MPC infusion resulted in a dose-related improvement in function, based on reduction in mean HAQ-DI levels as early as week 4 and sustained reduction in mean HAQ-DI through 12 weeks; maximal effect was seen in the 2M/kg group who had previously received 1-2 biologics…. At 12 weeks, MPC treatment resulted in a dose-related increase in the number of patients achieving a minimum clinically important improvement in physical function, defined as a reduction of at least -0.22 in the HAQ-DI; the greatest effect was seen in the 2M/kg group who had previously received 1-2 biologics….

“A single MPC infusion resulted in a dose-related reduction in the mean DAS28 activity score relative to placebo, and in an increase in the number of patients achieving the biologically meaningful target of low disease activity state, defined as DAS28-CRP <3.2.”

Dr. Gibofsky told OTW, “I am most encouraged by the fact that a single infusion resulted in durable efficacy with no significant safety issues.

“It may be possible to reduce or in some patients even eliminate the need for medications that have significant safety issues in our patients with rheumatoid arthritis, thus improving functional ability and health-related quality of life in our patients with rheumatoid arthritis.”