Enrollment in the 60-patient open label Phase 3 trial is ongoing across multiple sites in the United States, trial completion is expected in the first half of 2017, and commercial launch activities are underway.
The independent Data Safety Monitoring Board (DSMB) notified Mesoblast that an interim analysis showed that the predefined Bayesian futility rule used to determine the probability of the trial’s success using the trial’s primary endpoint of Day 28 overall response had been passed.
The analysis method determined the likelihood of obtaining a statistically significant treatment effect at study completion, based on the data observed at this interim time point.
There are currently no products approved in the United States for this disease. Japan is the only jurisdiction where this therapy is available, through Mesoblast’s licensee JCR Pharmaceuticals Co.
Based on guidance from the United States Food and Drug Administration (FDA), Mesoblast believes that positive data from this Phase 3 trial may be sufficient for filing for accelerated approval of MSC-100-IV in the United States. Mesoblast plans to broaden its use in adult patients with high-risk steroid-refractory aGVHD.
Joanne Kurtzberg, the Jerome Harris Distinguished Professor of Pediatrics and Director of the Pediatric Blood and Marrow Transplant Program at Duke University Medical Center and the lead investigator on the ongoing Phase 3 trial, said: “We are pleased that Mesoblast has attained such an important milestone in making its product available for the potential treatment of steroid-refractory acute graft versus host disease, a serious and life threatening condition that has a very urgent need for effective therapies.
“Mortality can reach 85% in patients with liver and gut complications and, outside of Japan, there are currently no approved therapies available. MSC-100-IV is on the cusp of becoming an important new treatment option for these patients,” she said.
The successful outcome of the DSMB interim analysis using the trial's primary endpoint of Day 28 overall response is consistent with previously reported results in a pediatric Expanded Access Program (EAP) in children with steroid-refractory aGVHD.
Results from this program, which evaluated MSC-100-IV in 241 children, were presented in February 2016 at the American Society of Blood and Marrow Transplantation annual meeting.
Key findings in the EAP program were:
- An overall response rate of 65% in all children at day 28 when MSC-100-IV was used either as last-line or front-line therapy after steroid failure
- An overall response rate of 81% at day 28 when MSC-100-IV was used as front-line therapy following steroid failure
- An overall response rate of 65% and 62%, respectively, in patients with gastrointestinal and liver disease, who have the highest mortality risk
- A significantly improved survival at day 100 in children who achieved overall response at day 28 (82% vs. 39%, log rank p-value <0.0001)
In February 2016, Mesoblast's licensee JCR launched TEMCELL® HS. Inj. in Japan, the first allogeneic cell-based product to receive full approval in the world’s second-largest standalone healthcare market.
A four-week, multi-dose treatment course of TEMCELL for an average adult is expected to be reimbursed by the Japanese Government’s National Health Insurance body at a minimum of ¥13,898,880 (approximately US$130,000) or up to ¥20,848,320 (approximately US$195,000) if symptoms persist and additional dosing is required.
Under its agreement with JCR, Mesoblast is entitled to receive royalties and other payments at predefined thresholds of cumulative net sales.
About Graft Versus Host Disease
Mesoblast is developing MSC-100-IV for the treatment of aGVHD following an allogeneic bone marrow transplant (BMT). In patients who have received a BMT, donor cells may attack the recipient (the person receiving the transplant), causing aGVHD, resulting in activation of pro-inflammatory T-cells and tissue damage in the skin, gut and liver, which is often fatal.
According to the Center for International Blood and Marrow Transplant Research, there are approximately 30,000 allogeneic BMTs globally per year for diseases including hematological cancers, with 25% of all cases in the pediatric population.
Nearly 50% of all allogeneic BMT patients develop aGVHD. Liver or gastrointestinal involvement occur in up to 40% of all patients with aGVHD and are associated with the greatest risk of death, with mortality rates of up to 85%.