Mesoblast (United States)

BACKGROUND: Acute graft-versus-host disease (aGVHD), a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT), often occurs within 100 days of HSCT. While steroids are typically used as first-line treatment, there is no consensus on second-line steroid-refractory (SR) treatments. SR aGVHD is associated with significantly worse pediatric health outcomes, but less is known about its economic impact. OBJECTIVE: To evaluate the economic burden of SR pediatric aGVHD in a commercially insured US patient population. METHODS: Retrospective analyses were conducted using medical and pharmacy claims data from the HealthCore Integrated Research Database (study period January 1, 2006-May 31, 2019). Included patients had at least 1 claim for allogeneic HSCT (earliest HSCT claim set as index date), no claims for autologous HSCT, and no pre-index GVHD. Patients were aged less than 18 years with no minimum pre- or post-index continuous enrollment. The GVHD cohort included patients with at least 1 claim for aGVHD over 100 days from index with at least 1 claim for any steroid and at least 1 claim for second-line therapy, both on or after the date of the first aGVHD claim. Patients post-HSCT with no GVHD claims over follow-up formed the comparison cohort. Health care resource utilization and costs over 12 months from the index date were calculated and compared between cohorts using parametric testing. RESULTS: 38 patients with SR aGVHD and 184 controls were included. Mean age and sex were similar for aGVHD (8.6 years, 50% female) and control (8.2 years, 45% female). During the 12-month post-index follow-up, SR aGVHD patients had higher rates of complications vs controls (* for P < 0.05): anemia (79% vs 68%), drug-induced anemia* (53% vs 34%), neutropenia (63% vs 53%), thrombocytopenia (58% vs 42%), gastrointestinal complications* (95% vs 65%), and infections* (95% vs 79%). Mean inpatient length of stay was longer by 31.6 days (P < 0.01) with a total average of 96.0 days for those with SR aGVHD vs 64.3 days for the controls. More SR aGVHD patients required inpatient total parenteral nutrition (71% vs 58%), readmission within 12 months of discharge from index hospitalization* (89% vs 60%), ER visits (34% vs 24%), and outpatient visits (100% vs 86%). Total 12-month mean medical costs were higher in aGVHD patients: $1,212,944 vs $673,491 (P < 0.001), mostly because of complication-related costs: $868,966 vs $396,757 (P < 0.001). Among patients with SR aGVHD, mean total costs were higher by about $1.8 million ($2,609,445 vs $812,385; P = 0.014) for those who died compared with those who were alive within 12 months. CONCLUSIONS: SR aGVHD in pediatric patients following HSCT is associated with incremental 12-month medical costs of greater than $500,000, driven largely by complications. DISCLOSURES: This research was sponsored by Mesoblast, Inc. Grabner is an employee of HealthCore, Inc., which acted as consultants to Mesoblast, Inc., during the conduct of this research. Strati is an employee of Mesoblast, Inc. Sandman and Forsythe are employees of Purple Squirrel Economics, which acted as consultants to Mesoblast, Inc., during the conduct of this research. This work was presented at the AMCP Annual Meeting online in April 2020 and was an encore presentation at AMCP Nexus 2020 Virtual in October 2020.

Brown, Stacey-Ann Whittaker; Iancu-Rubin, Camelia; Aboelela, Adam; Abrahams, Alex; Burke, Elizabeth; Drummond, Tiffany; Grossman, Fred; Itescu, Silviu; Lagdameo, Jonathan; Lin, Jung-Yi; Mark, Alexis; Levine, John; Osman, Keren Author Information

This paper considers the analysis of a repeat event outcome in clinical trials of chronic diseases in the context of dependent censoring (e.g. mortality). It has particular application in the context of recurrent heart failure hospitalisations in trials of heart failure. Semi‐parametric joint frailty models (JFMs) simultaneously analyse recurrent heart failure hospitalisations and time to cardiovascular death, estimating distinct hazard ratios whilst individual‐specific latent variables induce associations between the two processes. A simulation study was carried out to assess the suitability of the JFM versus marginal analyses of recurrent events and cardiovascular death using standard methods. Hazard ratios were consistently overestimated when marginal models were used, whilst the JFM produced good, well‐estimated results. An application to the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity programme was considered. The JFM gave unbiased estimates of treatment effects in the presence of dependent censoring. We advocate the use of the JFM for future trials that consider recurrent events as the primary outcome. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Mesenchymal stromal cells (MSCs) as a pharmaceutical for ailments characterized by pathogenic autoimmune, alloimmune and inflammatory processes now cover the spectrum of early- to late-phase clinical trials in both industry and academic sponsored studies. There is a broad consensus that despite different tissue sourcing and varied culture expansion protocols, human MSC-like cell products likely share fundamental mechanisms of action mediating their anti-inflammatory and tissue repair functionalities. Identification of functional markers of potency and reduction to practice of standardized, easily deployable methods of measurements of such would benefit the field. This would satisfy both mechanistic research as well as development of release potency assays to meet Regulatory Authority requirements for conduct of advanced clinical studies and their eventual registration. In response to this unmet need, the International Society for Cellular Therapy (ISCT) addressed the issue at an international workshop in May 2015 as part of the 21st ISCT annual meeting in Las Vegas. The scope of the workshop was focused on discussing potency assays germane to immunomodulation by MSC-like products in clinical indications targeting immune disorders. We here provide consensus perspective arising from this forum. We propose that focused analysis of selected MSC markers robustly deployed by in vitro licensing and metricized with a matrix of assays should be responsive to requirements from Regulatory Authorities. Workshop participants identified three preferred analytic methods that could inform a matrix assay approach: quantitative RNA analysis of selected gene products; flow cytometry analysis of functionally relevant surface markers and protein-based assay of secretome. We also advocate that potency assays acceptable to the Regulatory Authorities be rendered publicly accessible in an “open-access” manner, such as through publication or database collection.