NEW YORK and MELBOURNE, Australia, Aug. 08, 2016 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO) (ASX:MSB) today announced that a single intravenous infusion of its proprietary allogeneic Mesenchymal Precursor Cell (MPC) product candidate, MPC-300-IV, was well tolerated and demonstrated a dose-related improvement in clinical symptoms, physical function, and disease activity relative to placebo through the 12 week primary endpoint in its Phase 2 trial in biologic refractory rheumatoid arthritis.
Dr Allan Gibofsky, Professor of Medicine and Public Health at Weill Cornell Medical College and Attending Rheumatologist at Hospital for Special Surgery in New York, commented: “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.”
Mesoblast’s 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 clinical response to at least one anti-Tumor Necrosis Factor (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 study was comprised of a 12 week primary study period with a 40 week follow-up for a study total duration of 52 weeks.
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 primary 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 American College of Rheumatology (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 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. Analyses were performed for the whole study population and for the pre-specified exploratory subgroup based on whether the subjects had previously received 1-2 or more than 2 biologic agents.
Key results at week 12, shown in detail in the table below, were:
2. ACR70/50/20 composite scores measuring degree of clinical responses to treatment:
3. HAQ-DI score measuring functional improvement following treatment:
4. DAS28 composite score measuring overall disease activity following treatment:
Summary of Key Efficacy Responses at Week 12:
|All Subjects||Subgroup with Prior Use of 1-2 Biologics|
2M/kg vs placebo
2M/kg vs placebo
|HAQ-DI LS mean change from baseline||-0.2||-0.3||-0.6||0.02||-0.1||-0.4||-0.7||0.03|
|DAS28-CRP LS mean change from baseline||-1.4||-1.3||-2.0||>0.1||-1.1||-1.8||-2.4||0.06|
Major advances in the treatment of RA using biologic agents have resulted in a $15 billion global market in 2015, which is projected to grow to over $18 billion in 2024. Over two million patients were treated for RA in the United States alone in 2015, with three million more people in the five major European markets and Japan. Despite the substantial advances in RA treatment using biologic agents such as anti-TNF agents, approximately one third of patients either do not respond sufficiently or cannot tolerate these agents due to infectious or other complications. In the United States, the anti-TNF refractory population is the fastest growing branded market segment, projected to increase by 8% annually and potentially higher with the expected market entry and greater availability of anti-TNF biosimilars.
Mesoblast Chief Executive Silviu Itescu said: “The Phase 2 trial results have indicated a strong efficacy signal and consistent effects of a single MPC infusion on clinical symptoms, functional abilities, and disease activity, without any serious adverse events. These results support the potential of our allogeneic cell therapy to be positioned as a first-line treatment option for biologic refractory patients, where there is a clear need for safe and effective treatments. Given the large market opportunity, our Tier 1 product candidate, MPC-300-IV, is well-positioned to advance through a strategic partnership into Phase 3 development for biologic refractory rheumatoid arthritis.”
About Rheumatoid Arthritis
RA is a chronic autoimmune disease of unknown etiology, affecting approximately one percent of the global population. The disease is attributed to chronic inflammation affecting the synovial membrane of multiple joints, which eventually leads to cartilage and bone destruction. The health-related quality of life in patients with RA is significantly impaired by pain, fatigue, and decline in musculoskeletal function. RA is associated with an increased risk of cardiovascular disease and mortality.
Standard criteria established by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) are used to assess the effectiveness of RA treatments. The ACR70/50/20 response is a composite measure based on achieving 70%/50%/20% improvement in tender joint or swollen joint counts plus improvement in three of the following:
The patient and physician global assessments and pain assessment are measured using a visual analogue scale on a scale of 0-100. The HAQ-DI assesses physical function in performing a variety of activities of daily living and yields a score ranging from 0-3 (lower is better). A reduction in the HAQ-DI score of -0.22 is the minimal clinically important difference.
The DAS28 is another validated RA disease activity index based on a 28 joint count. The derived DAS28 scores are comprised of tender joint count; swollen joint count; acute phase reactant (hsCRP or ESR) and the subject’s global assessment of disease but do not include measures of pain or physical function. High disease activity is defined as DAS28 score >5.1; moderate disease activity is defined as DAS28 scores between 5.1-3.2; low disease activity and remission are defined as DAS28 scores of <3.2 and <2.6, respectively.
About Mesoblast's Product Candidate MPC-300-IV and Potential Mechanisms of Action
Mesoblast’s Tier 1 product candidate, MPC-300-IV, comprises 2 million immunoselected and culture-expanded Mesenchymal Precursor Cells (MPCs)/kilogram which are intravenously delivered. Existing biologic therapies target individual cytokine pathways thought to be involved in RA disease pathogenesis, including TNF-alpha, interleukin-6, or interleukin-17, but not concomitantly. There are at least two mechanisms of action (MOA) by which MPC-300-IV may impact on clinical rheumatoid arthritis outcomes through concomitant inhibition of multiple cytokine networks:
In large animal studies, a single intravenous infusion of Mesoblast’s allogeneic MPCs resulted in concomitant inhibition of TNF-alpha, IL-6 and IL-17 inflammatory pathways in the inflamed joints, and substantially ameliorated clinical disease. Biologic refractory RA patients who have received prior anti-TNF or other biologic agents continue to have active inflammatory pathways, and the broad, concomitant targeting of multiple cytokine networks by MPCs may result in clinically meaningful outcomes in this patient group.
Mesoblast Limited (ASX:MSB; Nasdaq:MESO) is a global leader in developing innovative cell-based medicines. The Company has leveraged its proprietary technology platform, which is based on specialized cells known as mesenchymal lineage adult stem cells, to establish a broad portfolio of late-stage product candidates. Mesoblast’s allogeneic, ‘off-the-shelf’ cell product candidates target advanced stages of diseases with high, unmet medical needs including cardiovascular conditions, orthopedic disorders, immunologic and inflammatory disorders and oncologic/hematologic conditions.
Conference Call and Webcast Details
Mesoblast will provide a corporate update beginning at 9:00 am Australian Eastern Standard Time on Tuesday 9 August 2016 / 7:00 pm Eastern Daylight Time on Monday 8 August 2016.
The live webcast can be accessed via: http://webcasting.boardroom.media/broadcast/579ff85b557172a161ada516
|To access the call, please dial:|
|Australia Toll Free||1 800 558 698|
|Australia Alternate||1 800 809 971|
|United States||1 855 881 1339|
|United Kingdom||0800 051 8245|
|Japan||0053 116 1281|
|Singapore||800 101 2785|
|Hong Kong||800 966 806|
|International||+61 2 9007 3187|
The conference identification code is 445377.
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For further information, please contact: Schond Greenway Investor Relations, Mesoblast T: +1 212 880 2060 E: firstname.lastname@example.org Julie Meldrum Corporate Communications, Mesoblast T: +61 3 9639 6036 E: email@example.com