Melbourne, Australia-based Mesoblast Limited announced promising data from a phase 2 trial of the company’s novel stem cell therapy for patients with rheumatoid arthritis (RA), which shows its therapeutic benefits continued 9 months after administration of a single intravenous (IV) dose.
The stem cell infusion of Mesoblast’s allogeneic Mesenchymal Precursor Cells (MPC)-300-IV was administered to 48 RA patients resistant to anti-Tumor Necrosis Factor (TNF) agents. A single IV dose of 2 million MPC/kg of MPC-300-IV was well tolerated and demonstrated a durable improvement in clinical symptoms, physical function, and disease activity relative to placebo over the follow-up period.
Approximately a third of RA patients develop resistance to TNF agents; others patients do not respond to the drugs or experience adverse events when using them. Second-line drugs such as Rituxan are not as effective as the anti-TNF agents and are associated with serious side effects.
The phase 2 study patients had active RA, were on a stable regimen of methotrexate, and had an inadequate prior clinical response to at least 1 anti-TNF agent. Of the 48 patients, 30 (68%) had previously received 1 to 2 biologic agents. Patients were randomized to a single IV infusion of 1 million MPCs/kg, 2 million MPCs/kg, or placebo. Patients were evaluated using the American College of Rheumatology (ACR) 20/50/70 measurement to assess clinical response and improvement in signs and symptoms of RA in terms of 20%, 50%, or 70% improvement from baseline. The study also used the ACR-N scale to assess mean or median magnitude of benefit, assessed health/disability with the HAQ-DI measure for functional status, and applied the DAS28 scale to measure RA disease activity in order to judge improvement.
The safety profile over 39 weeks was comparable among placebo and both MPC treatment groups, with no cell-related serious adverse events. Both MPC doses tested outperformed placebo at week 39 in each of the ACR20/50/70 responses. The 2 million MPCs/kg dose was found to be the most effective over 39 weeks; that dose also achieved the maximal ACR-N score earlier (at 12 weeks) and exhibited a more robust durable effect.
Mesoblast CEO Silviu Itescu said the company’s MPC therapies have demonstrated virtually no toxicity, and had generated no negative immune response. The cells also appear to be targeted, intrinsically moving toward sites of inflammation and embedding in tissue, he said. Receptors on the cells’ surface are activated by every major cytokine that is important in progressive RA, including TNF, interleukin (IL)-1, IL-6, and IL-17. Itescu believes MPC-300-IV has an edge on the biologics inhibiting TNF-alpha or other key targets because it is getting to the heart of the inflammation and disease, not just knocking back the immune system.
Although larger phase 3 studies are needed to validate these results, the data are intriguing in that they suggest what optimized and targeted regenerative medicines could potentially accomplish to address the unmet medical need among anti-TNF—resistant RA patients.