A remarkable new Canadian report provides a snapshot of the state of “novel” stem cell clinical trials — those not about bone marrow transplantation for blood-based cancers — around the world.
Published in Regenerative Medicine, The global landscape of stem cell clinical trials goes a long way to separate the hype from the hope around stem cell research and development.
The basic message of what the authors call “the most comprehensive account of the global stem cell clinical trial landscape to date” might be condensed to that recently refreshed British maxim from the Second World War: Keep calm and carry on.
“People have done it in a less systematic way,” says co-author Prof. Tania Bubela of other attempts to capture the global stem cell landscape. “But they didn’t work out what’s new.”
Prof. Bubela, a lawyer and Associate Professor at University of Alberta School of Public Health, wrote the report with lead author Dr. Matthew D. Li of the Stanford University School of Medicine, and Dr. Harry Atkins, a clinician/researcher at the Ottawa Hospital Research Institute who specializes in stem cell transplantation for the treatment of autoimmune diseases.
They looked at every stem cell trial listed in worldwide registries up to Dec. 31, 2012. Of the 4,749 studies, almost 80% involve improving bone marrow transplantation using hematopoietic (blood-forming) stem cells to treat leukemia and other blood-based cancers — or treating transplant-related conditions.
That work has been going on for five decades, with more than 1 million transplants performed so far. It’s no surprise, then, that so many trials are being carried out in countries with established infrastructure for bone marrow transplantation. It shows that developing clinical capacity and technical infrastructure to process and deliver cell therapies will be crucial to the ongoing development of regenerative medicine.
Setting those trials aside leaves 22% — or 1,058 clinical trials — testing novel therapies for a variety of maladies ranging from kidney conditions (eight clinical trials) to cardiovascular disease (278). It’s on these non-traditional trials that the report focuses.
And the findings are enlightening:
- In spite of enormous media attention, embryonic stem cells are being used in just a handful of clinical trials worldwide.
- The use of allogeneic (donated) stem cells “has increased rapidly since 2009” but autologous procedures (using a patient’s own stem cells) still prevail.
- Asian countries — especially China, but also South Korea, India and Japan — have surpassed the United States and Europe in volume of novel clinical trials. Trials are also increasing in Australia, Brazil, Iran and Israel.
- Industry partners are involved at least 25% the time, up significantly since 2004. This is particularly true in American states such as California, where 50% of all trials involve industry sponsorship or collaboration.
- Big pharma, however, is still on the fence: worldwide, most of the companies involved in novel trials are small to medium sized.
- Despite gaps in knowledge about the duration of their survival and impact on surrounding tissues, mesenchymal stem cells (found in bone marrow, umbilical cord blood ,muscle and fat tissue) are being used Phase 2 trials for diabetes, pulmonary hypertension, chronic obstructive pulmonary disease because of their “regenerative and reparative” potential.
Prof. Bubela makes the point that not all clinical trials are created equal. Regarding the proliferation of trials in Asia, she cautions that “just because they are listed in a registry doesn’t mean they have proper oversight or regulatory approval.” Some, she says, may be run by stem cell tourism operations — clinics that entice North Americans and Europeans to travel to their centres for unproven treatments that cost many thousands of dollars.
“You could speculate that they could be using it (the clinical trial) as a recruitment tool or for some form or legitimacy for the work they are doing.“
The report stresses that despite pressure from “patient groups desperate for therapies and cures for currently untreatable conditions” and “industry and policy makers eager to see a return on substantial investments,” moving treatments from clinical trials to clinical practice is going to take some time.
“If you look at the trajectory of any complex biologic (treatment), from R&D through regulatory processes, that just gives you market approval — it doesn’t give you a market,” says Prof. Bubela. “You still need to get clear reimbursement thresholds established. To get the complicated stuff through, you can be looking at 20-30-year development pipelines.”
The report concludes that “the field is progressing at a steady pace, but the therapeutic rhetoric must be tempered to reflect current clinical and research realities.”