Biologic Refractory Rheumatoid Arthritis

MPC-300-IV is our Phase 2 product candidate using mesenchymal precursor cells (MPCs) being developed for biologic-refractory rheumatoid arthritis.

Disease Indication and Patient Population

Rheumatoid arthritis (RA) is a chronic progressive disease causing inflammation in the joints and resulting in painful deformity and immobility, especially in the fingers, wrists, feet, and ankles. It affects approximately 1.7 million people in the United States. The incidence increases with age, climbing from 8.7 per 100,000 for those 18-34 years of age, to 89 per 100,000 for those 65-74 years of age. RA is responsible for up to 250,000 hospitalizations and 9 million physician visits per year1.

If left untreated, RA can lead to joint destruction, deformity, disability, and decreased quality of life. Existing biologic therapies have made major inroads to the treatment of RA. However, despite the variety of options available, approximately one third of patients do not respond or cannot tolerate these therapies.

Additionally, as these therapies carry a significant risk of opportunistic infections or malignancies, there is a need for an alternative therapeutic approach which is both safe and effective.


MPC-300-IV is a tier 1 product candidate comprising 300 million Mesenchymal Precursor Cells (MPCs) which are intravenously delivered.

Mechanism of Action

Pro-inflammatory monocytes/macrophages and activated T cells are involved in the pathogenesis of RA via activation of multiple pro-inflammatory cytokine pathways. Existing biologic therapies target these pathways, which include TNF-alpha, interleukin-6, and interleukin-17 individually, but none target all concomitantly. In preclinical large animal studies, it was demonstrated that a single intravenous injection of our allogeneic MPCs results in concomitant inhibition of TNF-alpha, IL-6 and IL-17 inflammatory pathways in the inflamed joints resulting in substantial amelioration in clinical disease.

Clinical Trials

Ongoing Phase 2 Trial

Mesoblast has completed enrollment in an ongoing 48-patient Phase 2 trial of MSC-300-IV in patients with active RA who have failed at least one TNF-a inhibitor.

Interim 12-week results from this study were reported in August 2016. The data show that MPC-300-IV was the first allogeneic MPC therapy to show positive effects on clinical symptoms, and function, in RA patients who had received at least one prior biologic agent. Patients demonstrated improvement as measured by the American College of Rheumatology (ACR) response, which is assessed in terms of 70%, 50% or 20% improvement from baseline; the health assessment questionnaire-disability index (HAQ-DI), a standardized measure of functional status; and the DAS28 composite measurement of disease activity.

In February 2017, 39-week data showed that a single intravenous infusion of MPC-300- IV was well tolerated and demonstrated a durable improvement in clinical symptoms, physical function, and disease activity relative to placebo over this period of follow-up.

Key outcomes were:

  • A single intravenous infusion resulted in durable responses through 39 weeks in patients resistant to anti-TNF agents
  • The safety profile over 39 weeks was comparable among the placebo and both MPC treatment groups, with no cell-related serious adverse events
  • Both MPC doses outperformed placebo at week 39 in each of ACR20/50/70 responses, as well as by median ACR-N analysis
  • Continuous variables ACR-N, HAQ-DI and DAS-28 were used in line with the FDA Guidance For Industry Rheumatoid Arthritis: Developing Drug Products For Treatment, May 2013, and identified the 2 million MPC/kg dose as the most effective over 39 weeks
  • The 2 million MPC/kg dose showed the earliest and most sustained treatment benefit.

In June 2017, safety and efficacy outcomes of the trial using pre-specified analyses over the 12-week primary evaluation period, as well as follow-up results over 39 weeks, were presented at the European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology.

Find out more about this Phase 2 trial


1Global Data Rheumatoid Arthritis Therapeutics – Pipeline Assessment and Market Forecasts to 2018. October 2011