When Japan’s landmark regenerative medicine legislation took effect in 2014, it opened an entirely new market for biotech innovators. Athersys, a leader in regenerative medicine, seized the opportunity.
When Japan’s landmark regenerative medicine legislation took effect in 2014, it opened an entirely new market for biotech innovators. Athersys, a leader in regenerative medicine, seized the opportunity.
Athersys’s MultiStem® cell therapy is in Phase III clinical trials in the U.S., and with Japanese partner Healios K.K. in Japan, to treat ischemic stroke and acute respiratory distress syndrome (ARDS). The therapy has the equivalent of Fast Track status in Japan. In the U.S., it is believed to be the only cell therapy treatment for ARDS that has both FastTrack and RMAT designations. Data readouts for the Japan trials are expected in early 2021.
Japan is an increasingly appealing market for regenerative medicine, in light of an increasingly elderly population and the nation’s commitment to regenerative medicine. “Most of our trans-Pacific focus for a number of years now has been on Japan,” Gil Van Bokkelen, Ph.D., Athersys’ founder, chairman and CEO, told BioSpace. “In Japan, like in the U.S., the standard of care is very good, but there are significant limitations for treating stroke, ARDS, and some other critical care conditions. Japan has the healthiest elderly population in the world, but stroke is a big problem there and throughout Asia.
“Historically, Japan suffered a lag in innovative medicines. At one point it took five years (on average) for them to enter the Japanese market,” he said.
Recognizing the problem that lag posed for its citizens, Japan’s government made revolutionary changes to expedite access to new treatments. Those changes enabled regenerative medicine therapies to be marketed for seven years under a conditional status while large Phase III trials are being conducted. As a result, “Many regenerative medicine companies are focusing on North America, Europe and Japan and several products have been approved under that framework,” Van Bokkelen said.
In contrast, “China and other Asian nations’ regulatory and commercial landscapes for regenerative medicine are still less defined than Japan’s,” Van Bokkelen said.
Although China represents a huge market opportunity in the future, its regulatory framework still is evolving.
In Japan, “Healios is getting close to complete enrollment in the 220-patient ‘Treasure’ study to evaluate MultiStem as an off the-shelf cell therapy for ischemic stroke,” he said.
The primary endpoint for that study is conducted three months after the stroke occurred. Healios and Athersys expect results by the middle of the second quarter 2021.
Importantly, in other trials for ischemic stroke, MultiStem showed consistent improvements from administration to the one-year follow-up.
“Conventional wisdom says that a patient’s state 90 days after a stroke is what they live with for the rest of their lives,” Van Bokkelen said. “If MultiStem is administered within 36 hours of the occurrence of a stroke, there was evidence of dramatic benefit based on the results from our previous clinical trial. Patients went from being disabled by the stroke to having good, excellent or, in some cases, complete recoveries,” Van Bokkelen said.
Healios is also running a 35-patient, open label study for ARDS that it expects to have fully enrolled by the end of the year. Called “One-Bridge,” this 28-day clinical assessment compares survival rates, length of time on ventilators and time spent in the ICU between patients administered MultiStem and those receiving the standard of care.
“The data that led to MultiStem’s Fast Track and RMAT designations showed a reduction in mortality as well as an increase in ventilator-free days and ICU-free days. Additionally, 45% of patients were ventilator free in seven days or less versus 20% for those receiving the standard of care,” Van Bokkelen said. “Our hope is that those improvements translate to Japan.”
One of the key questions for ARDS is whether MultiStem is merely helping patients survive, or whether it also is improving quality of life. To determine that, Athersys and Healios will continue studying the patients for one year to account for the dramatic differences in long-term outcomes seen in other studies.
Participants in the previously completed Athersys ARDS study were evaluated over a full year to quantify functional independence. Then the EQ-5D quality of life assessment was administered.
The results showed that 80% of MultiStem patients had achieved complete functional independence vs. only 40% of those receiving placebo. When patients evaluated their own quality of life, those treated with MultiStem scored in the 95-100% range, versus the 40-50% range for those receiving the standard of care.
“That’s a huge difference and has direct bearing on whether patients can return to work or their normal lives,” he said.
Although the science is the fundamental element of a good partnership, understanding the partners may be equally important, said Ivor Macleod, CFO of Athersys. That starts with “good alignment on the fundamental issues,” followed by good communication and a genuine commitment to meeting the needs of the partners in the project.
In Asia in particular, it’s also important to understand the difference between the public face and the private face.
“Things are done by consensus in Japan,” Macleod said. As he quickly learned while CFO of Eisai Inc. (the U.S. subsidiary of the Japanese company Eisai Ltd.), “By the time you got to the meeting, the decisions were already made. The trick was to involve yourself early in the decision-making process. That was very different from working in my previous company.”
Athersys is ranked number three among regenerative medicine companies on the NASDAQ, in terms of market capitalization. Now in partnership with Healios, Athersys is on the verge of transitioning from a startup to a commercial company.
“If we are successful in Japan, that day isn’t too far off,” Van Bokkelen, said.
