Athersys, Inc. got a major nod from Japan’s Pharmaceutical and Medical Devices Agency (PMDA) review of the Clinical Trial Notification (CTN), allowing the commencement by HEALIOS K.K. (Healios) of a confirmatory clinical trial evaluating the safety and efficacy of administration of MultiStem®, Athersys’ novel cell therapy product, for the treatment of ischemic stroke in Japan (also designated by Healios as HLCM051 in Japan).
In accordance with the regulatory system in Japan, a CTN is equivalent to an Investigational New Drug application, or IND, under the regulatory system used in the United States. This clinical trial to be conducted in Japan is part of a partnership and license agreement between Healios and Athersys, focused on the development and commercialization in Japan of novel cellular therapies, including MultiStem, for the treatment of ischemic stroke and potentially other indications. The study design was accepted as proposed to PMDA in the CTN.
“This announcement demonstrates exciting and important progress, achieved within less than eight months of launching the collaboration, and reflects the tremendous effort on the part of the teams at both organizations that are working together to advance this program in a highly focused and efficient manner,” said Gil Van Bokkelen, Ph.D., Chairman and Chief Executive Officer of Athersys. “The development approach being taken by Healios and Athersys in Japan is consistent with the approach we plan to implement in a separate international study. Both studies are designed to provide the confirmatory evidence that we believe will put us in a strong position to obtain approval in one of the greatest areas of unmet clinical need in medicine today.”
The planned study will be a randomized, double-blind, placebo-controlled clinical trial conducted at hospitals in Japan that have extensive experience at providing care for stroke victims. Based on the experience from the B01-02 study, subjects enrolled in the trial will receive either a single dose of MultiStem or placebo, administered within 18–36 hours of the occurrence of the stroke, in addition to standard of care. As previously disclosed, the study will evaluate patient recovery through approximately 90 days following initial treatment based on Excellent Outcome and other neurological, functional and clinical endpoints. Additional patient follow up will occur through one year, and other design elements of the Japan trial are consistent with a planned international Phase 3 study, and what has been described previously at the Stroke 2016 conference held in Sapporo earlier this year.
The trial in Japan follows a Phase 2 study completed by Athersys, referred to as the B01-02 trial, which was conducted at 33 clinical sites in the United States and United Kingdom. The study evaluated the safety and effectiveness of the intravenous administration of MultiStem cells within 24–48 hours after the occurrence of a moderate to severe stroke. The evaluable patient population comprised 126 subjects who were treated with MultiStem therapy or placebo.
As disclosed previously, intravenous administration of MultiStem following an ischemic stroke was well tolerated, consistent with observations from other clinical trials evaluating the safety of MultiStem treatment. Additionally, among all evaluable subjects in the B01-02 study, a greater percentage of subjects in the MultiStem group (15.4%) had an Excellent Outcome (mRS ≤1, NIHSS ≤1, and Barthel Index ≥95) at day 90 compared to the placebo group (6.6%) (p=0.10). At one year, a greater percentage of subjects in the MultiStem group had an Excellent Outcome compared to the placebo group (23.1% vs. 8.2%, p=0.02). For the MultiStem subjects treated within 36 hours of the stroke (i.e. the target population in the planned Japan study), the difference in Excellent Outcome was even greater (e.g., at one year, 29.0% vs. 8.2%, p<0.01). Likewise, other measures of functional recovery, including the mRS distribution or “shift” analysis, biomarker data and clinical outcomes, including shorter hospitalization, less time in the Intensive Care Unit, and lower rates of mortality and life threatening adverse events, suggest that MultiStem treated patients experienced an improved recovery from post-stroke neurological complications.
“We are excited about reaching this point and about the degree of enthusiasm expressed for the study at the clinical investigators meeting recently held in Tokyo. With the CTN now in effect, the next steps in the process prior to the initiation of enrollment include obtaining Institutional Review Board approval and finalizing agreements with each of the participating clinical sites. In the near term, Healios will be focusing on these activities, while Athersys provides support in other areas in preparation for the commencement of enrollment,” concluded Dr. Van Bokkelen.
Stroke represents an area where the clinical need is particularly significant, since it is a leading cause of death and serious disability worldwide, with a substantially impaired quality of life for many stroke victims. Currently, there are nearly 17 million people that suffer a stroke globally and more than two million stroke victims each year in the United States, Europe and Japan, combined. Ischemic strokes, which represent the most common form of stroke, are caused by a blockage of blood flow in the brain that cuts off the supply of oxygen and nutrients and can result in long-term or permanent disability due to neurological damage. Unfortunately, current therapeutic options for ischemic stroke victims are limited, since the only available therapies, administration of the clot dissolving agent tPA, or “thrombolytic,” or surgical intervention using mechanical reperfusion to remove the clot, must be conducted within several hours of the occurrence of the stroke. As a consequence of this limited time window, only a small percentage of stroke victims are treated with the currently available therapy—most simply receive supportive or “palliative” care. The long-term costs of stroke are substantial, with many patients requiring extended hospitalization, extended physical therapy or rehabilitation (for those patients that are capable of entering such programs), and many require long-term institutional or family care.