Athersys Inc. announced positive results from its Phase 1 clinical trial of MultiStem administered to individuals undergoing allogeneic hematopoietic stem cell transplants (HSCT) for the treatment of leukemia and related conditions.

The study demonstrated that MultiStem therapy was well-tolerated in both the single infusion and repeat infusion arms and suggested the therapy may provide benefit to recipients of allogeneic HSCT, such as reducing the incidence and severity of Graft-versus-Host Disease (GvHD). The results are consistent with previous preclinical studies that show that MultiStem provides multiple benefits in HSCT and other transplant models, such as reducing inflammatory damage and promoting graft acceptance.

The majority of patients participating in the study received transplants from unrelated donors and nearly all of the patients received peripheral blood stem cell (PBSC) transplants. All patients experienced successful neutrophil engraftment, and 86% of patients experienced successful platelet engraftment.

There was a substantial reduction in acute GvHD incidence, at the highest single dose (11% grade II-IV GvHD, and 0% grade III-IV GvHD). Evidence was shown of a dose response relationship, with patients receiving the highest single dose of MultiStem having a 33% lower absolute incidence of acute GvHD relative to patients who received a single low or medium dose, and patients receiving once weekly dosing of the medium dose through the first 30 days having reduced GvHD incidence relative to single or weekly dosing over the first two weeks post-transplant. There was a favorable relapse-free survival (RFS) rate at 100 days among all patients and there was limited infection-related complications over the first 100 days.

During the first 48 hours following MultiStem administration, patients were assessed for infusion-related toxicity and other acute adverse events. The primary endpoint for the study was the determination of the maximum tolerated dose, as determined by a continual reassessment methodology. Regimen-related toxicities and infusion-related allergic toxicities through 30 days after MultiStem administration were also monitored. Additionally, patients were evaluated for adverse events and infections through 100 days following the HSCT.

The administration was found to be well-tolerated for all dosing groups in both the single and repeat dose administration arms. Immediately following dosing, there were no clinically significant changes to vital signs or evidence of allergic reaction associated with MultiStem administration. Over the 30-day observation period, no infusional toxicities or clinically significant adverse events occurred.

MultiStem had a favorable safety profile over the 100-day period following the HSCT with no graft failures. Of the 36 patients in the study, 30 patients completed 100 day follow-up and there were six withdrawals, including two relapses and three deaths (unrelated to treatment). Other serious adverse events in the first 100 days were consistent with expectations for the patient population.

Following MultiStem administration, patients were assessed weekly by the attending physician for GvHD (and regimen-related toxicities), and information regarding infections and adverse events was collected as they occurred, through day 100.

Overall, MultiStem treatment was associated with a positive impact on blood and immune system recovery, with 100% neutrophil and 86% platelet engraftment for study patients. The median time to engraftment was 15 days for neutrophils and 16 days for platelets.

The cumulative incidence of acute GvHD for all subjects enrolled in the study was generally in line with expectations for the patient population based on historical experience and scientific literature, using Kaplan-Meier estimates censored for study withdrawal due to relapse and death. However, in the highest single dose group (10 million cells per kilogram body weight, infused on day 2 following HSCT), the 100-day cumulative incidence of moderate to severe acute GvHD was 11%, which compares favorably with historical experience for the patient population (generally 40-60% grade II-IV GvHD), and, among the patients in this group, no patient developed severe GvHD. Additionally, at the five million cells per kilogram body weight dose level, once weekly dosing of the intermediate dose through the first 30 days provided apparent additional benefit over single or weekly dosing over the first two weeks post-transplant.

MultiStem was associated with a relatively low level of late stage infection and only one case of infection-related mortality occurred through 100 days. Overall, the Kaplan-Meier estimate of relapse-free survival at 100 days was 81%.

Athersys received orphan drug designation from the U. S. Food and Drug Administration for prevention of GvHD in September 2010.

Athersys plans to meet with the FDA to discuss plans for the next phase of clinical development, which could include a blinded, controlled Phase 2/3 study of MultiStem for GvHD prophylaxis and HSCT support. The study would be intended to help lay the groundwork for approval in the indication, but would also help continue to establish the scientific foundation for MultiStem in related areas including GvHD treatment, solid organ transplant, and other areas of immune system dysfunction.

Release Date: Feb. 1, 2012
Source: Athersys Inc.