Date: 2015-02-16
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the 2016 International Stroke Conference in Los Angeles
Company: Athersys (USA - OH)
Product: MultiStem®
Action
mechanism: stem cell therapy. MultiStem® cell therapy is a patented regenerative medicine product that has shown the ability to promote tissue repair and healing in a variety of ways, such as through the production of multiple therapeutic factors produced in response to signals of inflammation and tissue damage. MultiStem has demonstrated therapeutic potential for the treatment of inflammatory and immune disorders, neurological conditions, and cardiovascular disease, as well as other areas. It represents a unique \"off-the-shelf\" stem cell product that can be manufactured in a scalable manner, may be stored for years in frozen form, and is administered without tissue matching or the need for immune suppression.
Disease: ischemic stroke
Therapeutic area: Cerebrovascular diseases
Country: UK, USA
Trial
details: The randomized, double-blind, placebo-controlled Phase 2 clinical trial is being conducted by Athersys at sites in the United States and United Kingdom, and has enrolled subjects who received either MultiStem treatment or placebo one to two days following the stroke. The primary endpoints for the study include safety over the first seven days following treatment and global stroke recovery at day 90, which assesses global disability (modified Rankin Score), neurological deficit (NIH stroke scale) and activities of daily living (Barthel Index). Additionally, there are multiple secondary and exploratory endpoints evaluating multiple elements of recovery and dysfunction, including biomarkers associated with the condition and recovery, and safety variables over the study period. The study was conducted in two parts - a small dose selection phase involving 16 patients in two cohorts, followed by larger efficacy phase of 118 patients. The evaluable patient population included 8 patients from cohort 2 and the cohort 3 patients, which all received a high dose of treatment or placebo. The study enrolled subjects who received either MultiStem treatment or placebo one to two days following the stroke. The primary endpoints for the study include safety over the first seven days following treatment and global stroke recovery at day 90, which assesses disability (modified Rankin Score ? 2), neurological deficit (NIH stroke scale, delta ?75%) and activities of daily living (Barthel Index ? 95%). Additionally, there are secondary and exploratory endpoints evaluating elements of recovery and dysfunction, including biomarkers associated with subject condition and recovery, and safety variables over the study period. Of the patients evaluated in the study, 65 patients were in the MultiStem treatment group and 61 patients were in the placebo group. Among the enrolled patients, the groups were generally evenly balanced in terms of baseline stroke characteristics.
Latest
news: * On February 17, 2016, Athersys, announced positive results from the analysis of one-year follow-up data from its Phase 2 clinical study of the intravenous administration of MultiStem® cell therapy to treat patients who have suffered an ischemic stroke. Dr. David Hess, lead clinical investigator of this study and a stroke specialist and Chairman of the Department of Neurology at the Medical College of Georgia, Augusta University, presented the summary results at the 2016 International Stroke Conference in Los Angeles. The one-year data demonstrates that MultiStem-treated subjects on average continued to improve through one year and had a significantly higher rate of “Excellent Outcome” (defined clinically as attaining mRS 0-1, NIHSS 0-1 and BI ?95) compared to placebo subjects at one year when evaluating all subjects enrolled in the study (p=0.02), i.e., the intent-to-treat population. The relative improvement in Excellent Outcomes was even more pronounced in the patients who received MultiStem treatment within 36 hours of the stroke (p <0.01). Data highlights from the 365-day follow-up data analysis include: MultiStem® treatment continued to be well tolerated through 365 days; Among all subjects who received MultiStem treatment (n=65), 23.1% of patients achieved an Excellent Outcome at 365 days, compared to 8.2% of patients who received placebo (n=61), and the 14.9% difference was statistically significant (p=0.02) and compared favorably to the 8.8% difference at 90 days; *p = 0.02, **p<0.01 Substantial improvements were also observed in the Barthel Index, which is the clinical scale used to assess the ability of patients to live independently. Among all subjects (65 MultiStem, 61 placebo), 61.5% of MultiStem patients had an excellent outcome in the Barthel Index (?95), compared to 44.3% of placebo patients (p=0.05); furthermore, 67.7% of the subset of MultiStem patients who had treatment within 36 hours (n=31) achieved an excellent Barthel outcome, representing a 23.4% difference with the incidence for all placebo patients (p=0.03); and * On April 17, 2015, Athersys announced interim results from its exploratory Phase 2 clinical study of the intravenous administration of MultiStem® cell therapy to treat patients who have suffered an ischemic stroke. The study results demonstrate favorable safety and tolerability for MultiStem®, consistent with prior studies. With respect to the primary and secondary endpoints, the cell therapy did not show a difference at 90 days compared to placebo. However, MultiStem® treatment was associated with lower rates of mortality and life threatening adverse events (AEs), infections and pulmonary events. Furthermore, post-hoc analysis shows that patients who received MultiStem® treatment earlier in the treatment window had more robust recovery rates in comparison to placebo and relative to patients who received later MultiStem treatment. Dr. David Hess, lead clinical investigator in the study, stroke specialist and Chairman of the Department of Neurology at the Medical College of Georgia at Georgia Regents University, will present the summary results at the European Stroke Organization conference on Sunday, April 19th. Data highlights from the 90-day interim analysis include: MultiStem® cell therapy demonstrated favorable tolerability and safety profile through the evaluation date, which was at least 90 days for all patients; Patients who received intravenous administration of MultiStem® did not show a significant difference from placebo-treated patients for the primary endpoint (Global Stroke Recovery Assessment) and the related secondary endpoints - which were defined as the proportion of patients achieving a modified Rankin Scale (mRS) value of 0-2, improvement in the NIH Stroke Scale (NIHSS) by ? 75% and achieving Barthel Index (BI) ? 95 at day 90, however Among all subjects who received MultiStem® treatment, 15.4% of patients achieved an Excellent Outcome, defined clinically as attaining mRS 0-1, NIHSS 0-1 and BI ?95, compared to 6.6% of patients that received placebo, (p=0.10); As described in the table below, patients who received MultiStem® treatment earlier in the treatment window (24-36 hours post-stroke) exhibited more favorable recovery on the primary and key secondary endpoints than patients who received placebo or patients who received MultiStem® treatment later (e.g. Excellent Outcome, p = 0.03), and this treatment effect was even more pronounced the earlier the MultiStem® administration within the 24-36 hour timeframe; A higher proportion of patients who received treatment with MultiStem® achieved a good clinical outcome by day 7 after treatment, defined as achieving mRS 0-2, which was 12.9% for patients receiving MultiStem®, compared to 5.2% of patients who received placebo, and a similar pattern was seen for improvement in NIHSS ? 75%, which was achieved by 10.2% of MultiStem treated patients vs. 3.9% of patients who were treated with placebo; Mortality was lower among patients who received treatment with MultiStem in comparison with placebo. There were 9 subject deaths (14.8%) among those receiving treatment with placebo, and only 4 patient deaths (6.2%) among patients receiving treatment with MultiStem®; The MultiStem® treatment group had a lower rate of life threatening adverse events and death (p=0.04), and also exhibited lower rates of pulmonary events (p=0.08) and infections. The MultiStem treated group also had a significantly lower level of circulating CD-3+ T-cells at two days following dosing (p < 0.01), suggesting a reduction in the inflammatory response post-stroke, consistent with the therapeutic hypothesis. MultiStem Administered ?36 Hours Compared to All Placebo* Characteristic MultiStem Placebo Age, mean (at time of admission) 61.6 62.5 % of male Subjects 52.2% 54.8% % of female Subjects 47.8% 45.2% NIHSS at baseline, mean 13.3 13.4 % of patients that received tPA 43.3% 48.4% * Excludes confounding data from patients that received both tPA and mechanical reperfusion in addition to investigational product ** Results for patients getting MultiStem administration > 36 hours not materially different from placebo * On December 29, 2014, Athersys announced that it has concluded patient enrollment of its Phase 2 clinical study involving administration of Athersys\' MultiStem® cell therapy to ischemic stroke patients. The study is a randomized, double-blind, placebo-controlled, multi-center clinical trial evaluating the safety and efficacy of MultiStem® therapy in subjects suffering moderate to moderate-severe ischemic strokes. Athersys expects initial results from the study to be disclosed around the end of the first quarter of 2015. In this Phase 2 trial, stroke victims were administered MultiStem® cells or placebo intravenously one to two days after the stroke had occurred. If this study shows that MultiStem treatment is both safe and effective following such administration, as was demonstrated in non-clinical studies, the treatment window could be expanded significantly, from hours to days, providing an important new therapeutic option for stroke patients. Based on preclinical studies, Athersys believes that MultiStem treatment has the potential to substantially improve neurological and functional recovery following stroke by attenuating the inflammatory activity that follows the stroke, accelerating the return to immune system homeostasis, supporting protection of at-risk neurons, and by supporting conditions for neuronal recovery and growth, thereby enhancing repair and patient recovery. The MultiStem treatment\'s potential multidimensional impact distinguishes the cell therapy from other pharmaceutical therapies focused on a single mechanism of benefit.
Among patients who received MultiStem treatment within 36 hours following the stroke, 29.0% achieved Excellent Outcomes (n=31), and compared to all placebo subjects (n=61), the 20.8% difference was significant (p<0.01) and also greater than the 9.5% difference at 90 days;Proportion of Subjects with Excellent Outcome at Day 90 and Over One Year Subjects Day 90 Day 365 All MultiStem (n=65) 15.4 % 23.1 % All Placebo (n=61) 6.6 % 8.2 % Difference with all placebo 8.8 % 14.9%* Early Treatment with MultiStem (n=31) 16.1 % 29.0 % Difference with all placebo 9.5 % 20.8%**
Among MultiStem patients who did not achieve an Excellent Outcome at 365 days, there appears to be meaningful benefit from the treatment relative to standard of care, with reductions in average initial hospitalization days, mortality, life threatening adverse events and infections. For example, comparing all such MultiStem and placebo subjects, MultiStem-treated patients had 1.6 fewer average hospitalization days, and an 11% lower proportion of patients with death or life threatening adverse events. In addition, when comparing subjects receiving early treatment with MultiStem against all placebo subjects, MultiStem patients had an average of 2.9 fewer hospitalization days, and an 11.4% lower incidence of death or life threatening adverse events. Further, such MultiStem patients appear to have better functional improvement than these placebo patients over one year, as evidenced by a higher proportion of excellent Barthel Index outcomes (?95), 50% for MultiStem subjects (and 55% for early treatment MultiStem), compared to 39% for placebo subjects.
As noted above, post-hoc analyses show that earlier MultiStem® administration appears to provide substantial benefit, as evident in the following table:
