Enrollment in Athersys stroke trial nears completion

Athersys (NASDAQ:ATHX) expects to complete enrollment by the end of the summer in a Phase 2 clinical trial of its MultiStem cell therapy in about 140 moderate to moderately-severe ischemic stroke patients, with data to be released before year end.

“If we get the results we’re looking for, this could have a dramatic impact on stroke medicine and greatly improve treatment for more severe stroke patients,” chairman and CEO, Gil Van Bokkelen, says in an interview with BioTuesdays.com.

Cleveland-based Athersys is developing MultiStem for the treatment of conditions in the cardiovascular, neurological, inflammatory and immune disease areas.

MultiStem is a biologic product manufactured from human stem cells obtained from adult bone marrow or other nonembryonic tissue sources. The stem cell product can be expanded on a large scale for future use and stored in frozen form until needed.

Cells obtained from a single donor do not require genetic modification and may be used to produce hundreds of thousands to millions of doses of MultiStem, an amount far greater than other stem cell types can achieve, Dr. Van Bokkelen contends.

“MultiStem expresses a combination of therapeutic proteins and factors to enhance healing and tissue repair in multiple ways,” he says. “The repair process includes inflammation reduction, neuroprotection and cytoprotection and promoting the formation of new blood vessels in areas of ischemic damage.”

According to Dr. Van Bokkelen, MultiStem’s window of therapeutic intervention appears to be much longer in stroke patients than currently available therapies such as Genetech’s tPA, which must be administered within three-to-four hours of ischemic stroke. As a result, tPA is currently used in less than 10% of treatable patients.

“Stroke clinicians tell us that within one-to-two days after a stroke, 95% or more of stroke victims could get to hospital for treatment,” he adds.

Ischemic stroke represents a major unmet medical need, with an annual market opportunity of more than $15-billion. He says that with an increasingly obese and aging population, the clinical need and commercial opportunity are expected to increase dramatically in the years ahead.

Dr. Van Bokkelen explains that in preclinical studies, MultiStem demonstrated “substantial and durable therapeutic benefits” even when it was administered seven days after an ischemic event, adding that earlier administration is better than late administration.

In the Phase 2 stroke trial, which is being conducted at leading stroke centers in the U.S. and U.K, patients are being treated one-to-two days after a stroke, with MultiStem administered intravenously. The first two dosing cohorts in the trial were judged to be safe and well tolerated.

The company also has initiated discussions with regulators in Japan. According to Dr. Van Bokkelen, there has been significant enthusiasm expressed among leading stroke clinical centers in Japan to conduct clinical trials with MultiStem.

Stroke is a leading cause of death and serious disability in Japan. Last November, Japan adopted a new approval system for cellular therapies that provides provisional approval after the confirmation of probable benefit or efficacy and safety, enabling earlier patient access to cellular therapies.

“There’s a great deal of excitement in Japan for regenerative medicine,” Dr. Van Bokkelen contends.

He says MultiStem has shown activity in other acute and chronic neurological indications, such as traumatic brain injury, spinal cord injury and multiple sclerosis.

In addition to ischemic stroke, Athersys has clinical programs underway with MultiStem in inflammatory bowel disease, acute myocardial infarction, solid organ transplant and graft-versus-host disease, a frequent complication associated with transplant procedures used to treat leukemia or related blood-borne cancers.

“Our portfolio of programs cuts across a broad number of therapeutic areas,” Dr. Van Bokkelen points out. “We don’t expect to be successful in all areas, but if the technology is successful in any area, it would have a dramatic impact on improving clinical outcomes, quality of life for patients and healthcare economics.”

The company has established sufficient safety data that it can move its programs directly into Phase 2 clinical development. And rather than build an internal infrastructure to pursue all these programs, he says Athersys collaborates with outside labs and investigators as a cost-effective approach to explore areas where MultiStem may be effective.

In acute myocardial infarction, he suggests that administration of MultiStem following a heart attack has the potential to improve outcomes and reduce the risk of progression to chronic heart failure.

Dr. Van Bokkelen says that in a Phase 1 trial conducted at the Cleveland Clinic and several other leading cardiovascular clinical centers, MultiStem established an excellent safety profile through one year, with meaningful improvements in left ventricular ejection fraction, stroke volume and heart wall motion.

Athersys has received FDA authorization to conduct a Phase 2 trial with MultiStem in acute myocardial infarction, which he says will begin later in 2014. The company already has received $2.8-million in funding for the trial from the National Institutes of Health.

Athersys is also working to finalize the design of a Phase 2/3 graft-versus-host disease prophylaxis study later this year.

Last month, Athersys announced interim results from the Phase 2 clinical study being conducted by Pfizer, in which MultiStem cell therapy is administered intravenously to treat patients with chronic, advanced ulcerative colitis (UC).

The study results demonstrated favorable safety and tolerability through eight weeks following treatment, but it failed to show meaningful benefit following a single administration of MultiStem.

“While we were disappointed with the recent failure, the study told us that one dose of MultiStem was not enough to get these chronic patients to where we wanted them,” Dr. Van Bokkelen says.

Additional 16-week results, including data about the impact from a second round of dosing for a subset of patients, longer-term secondary clinical endpoints and biomarker evaluation, will be available after additional analysis has been completed, he adds.

“In the meantime, we have a strong balance sheet, and we are pursuing multiple exciting opportunities where we remain confident MultiStem will have an important impact,” he says.