MESO 5.10 0.09 1.80 % : Mesoblast Limited - American De - Yahoo Finance
November 11, 2017
Comment
NEW YORK and MELBOURNE, Australia, Nov. 10, 2017 (GLOBE NEWSWIRE) -- Mesoblast Limited (ASX:MSB) (MESO) today announced that results from the randomized, placebo-controlled Phase 2 trial of its proprietary allogeneic mesenchymal precursor cells (MPCs) over 52 weeks in patients with biologic refractory rheumatoid arthritis (RA) were presented at the 2017 American College of Rheumatology (ACR) Annual Meeting held this week in San Diego, CA.
The abstract was submitted for peer review by the trial’s lead investigators, Dr. Suzanne Kafaja, Assistant Clinical Professor, and Dr. Daniel E. Furst, Professor of Medicine in the Division of Rheumatology, Department of Medicine, at the University of California at Los Angeles (UCLA). The ACR Annual Meeting is attended by approximately 16,000 delegates from more than 100 countries.
Dr. Kafaja said: “The clinical responses in this Phase 2 trial, together with the safety profile, position MPC-300-IV to become an early treatment option in rheumatoid arthritis patients who are resistant to or intolerant of anti-TNF or other biologic agents.”
The Phase 2 trial recruited a total of 48 patients with active RA who were on a stable regimen of methotrexate and had an inadequate prior response to at least one anti-TNF agent. Of the 48 patients, 30 (63%) had previously received 1-2 biologic agents. Patients were randomized to a single intravenous infusion of 1 million MPCs/kg (1M/kg, n=16), 2 million MPCs/kg (2M/kg, n=16) or placebo (n=16).
The primary objective of the study was to evaluate safety and tolerability of a single intravenous MPC infusion in these biologic refractory RA patients through a 12-week primary endpoint. Additional objectives were to evaluate clinical efficacy at the 12-week endpoint and to assess the durability of effects and safety profile through the full 52-week study.
Pre-specified efficacy endpoints included the following: ACR composite clinical response, which is an endpoint used in RA clinical trials to measure improvement in signs and symptoms of the disease in terms of 20%, 50% or 70% improvement from baseline; ACR-N which measures the mean or median magnitude of benefit using an ACR composite for a typical patient; the health assessment questionnaire-disability index (HAQ-DI), a standardized measure of functional status; the short-form health survey (SF-36), an assessment of health-related quality-of-life; and the measure of disease activity in 28 joints (DAS28) composite measurement of disease activity; no adjustment for multiplicity was performed as these efficacy endpoints were exploratory and the trial was not powered for efficacy.
Additionally, continuous variables ACR-N, HAQ-DI and DAS-28 were evaluated in a pre-specified manner since the use of endpoints sensitive to change provide better discriminatory power for dose-response assessment, in line with the FDA Guidance For Industry Rheumatoid Arthritis: Developing Drug Products For Treatment, May 2013.
Analyses were performed for the whole study population and for the pre-specified exploratory subgroups based on whether the subjects had previously received 1-2 biologic agents or more than 2 biologic agents.
Key findings:
• Infusions were well-tolerated and there were no treatment-related serious adverse events reported during the 52-week period, with the safety profile over 52 weeks comparable among the placebo and two MPC treatment groups.
• A single intravenous MPC infusion in biologic refractory RA patients resulted in dose-related improvements in clinical symptoms, function, disease activity and patient-reported outcomes. Efficacy signals were observed for each of ACR 20/50/70, ACR-N, HAQ-DI, SF-36 and DAS-28 disease activity score.
• The 2 million MPC/kg dose showed the greatest overall treatment responses. Onset of treatment responses occurred as early as 4 weeks, peaked at 12 weeks, were maintained through 39 weeks, and waned by 52 weeks.
• Greatest benefits over 52 weeks were seen in patients who had failed less than 3 biologics (1-2 biologic sub-group) prior to MPC treatment, identifying this as a potentially optimal target population.
• The following statistically significant outcomes were observed over the 52-week study period:
At 4 weeks:
- the MPC 2M/kg group had significantly better outcomes than placebo for improvement in pain, as measured by the ACR domain for subjective assessment of pain (p=0.04) and the SF-36 domain for bodily pain (p=0.014)
- the MPC 2M/kg group had significantly better outcomes than placebo for improvement in physical function, as measured by the SF-36 physical component summary score (p=0.015) and physical function score (p=0.002), as well as the HAQ-DI mean change from baseline (p=0.043)
At 12 weeks:
- the MPC 2M/kg group had significantly better outcomes than placebo for both the composite ACR70 response (p=0.043) and the overall ACR-N Area Under the Curve, AUC (p=0.05)
- the MPC 2M/kg group had significantly better outcomes than placebo for the ACR domains of subject’s assessment of pain (p=0.039) and subject’s assessment of disease activity (p=0.04)
- the MPC 2M/kg group had significantly better outcomes than placebo for proportion of patients achieving minimally important improvement in HAQ-DI function score (p=0.003) as well as the HAQ-DI mean change from baseline (p=0.018)
- the MPC 2M/kg group had significantly better outcomes than placebo for several domains of the SF-36 composite score, including physical component summary score (p=0.018), bodily pain (p=0.03), and role physical (p=0.014)
At 12, 39 and 52 weeks:
- the MPC 2M/kg group significantly outperformed placebo at every time point for ACR-N Area Under the Curve (AUC) (p=0.05 at 12 weeks, p=0.004 at 39 weeks, and p=0.008 at 52 weeks), indicating a robust, durable and consistent clinical effect of this MPC dose.
Mesoblast Chief Medical Officer Dr. Donna Skerrett said: “We are very pleased with the results of this Phase 2 trial, which identified a dose-related treatment effect, the earliest onset of the effect, and the durability from a single dose. Given the excellent safety profile, we intend to evaluate whether higher MPC doses can achieve even greater rates of low disease activity or remission within the first 12 weeks and beyond. We also plan to evaluate whether the observed durable treatment responses can be maintained for the longer term using repeat dose therapy.”