Another World-First As Japan OKs Spinal Injury Cell Therapy Trial
Executive Summary
In another globally pioneering move, Japan approves a trial with its flagship iPS cell technology in spinal cord injury, following a controversial earlier marketing approval in the same indication.
Despite controversy over a recent pioneering marketing approval of a cell-based therapy for spinal cord injury, Japan has taken another world-leading step in this arena as it looks to build a global leadership position.
An advisory panel to the country's ministry of health, labour and welfare has allowed for the first time globally a clinical study with another form of cell therapy in the same indication, giving the nod on Jan. 18 to a small trial using induced pluripotent stem cells (iPSCs).
The planned four-patient study, in adults with spinal cord injuries that have affected movement and neurological function, will be led by researchers at Keio University in Tokyo under Professor Hideyuki Okano, who said it will start within this year, possibly in the summer.
The iPSCs, sourced from an existing bank at Kyoto University's Center for iPS Cell Research and Application, will be directed to differentiate into neuronal cells, which will then be injected within two to four weeks of the original injury.
The maximum "dose" will be two million cells, although this may be raised to 10 million as the study progresses and depending on initial response, and the researchers said they hope for initial findings within a year or so of the trial start. Earlier primate studies have already showed some positive impact on restoring motor function, the researchers said.
The participants will also receive standard immunosuppressant therapy to dampen potential rejection and other medication during the trial.
Steaming Ahead
The regulatory clearance marks the fifth time a clinical study with iPSCs (mostly university-led programs) has been allowed in Japan, where the government sees the country as a leader in the field following the 2012 Nobel Prize win by iPSC pioneer Shinya Yamanaka of Kyoto University.
The cells, which can be derived from skin and other organs, have the ability to be directed through genetic manipulation to transform into almost any cell type of cell, aiding functional organ regeneration.
A clear and highly supportive policy and regulatory framework for cell and regenerative therapies has been enacted, including revised and new dedicated regulations that came into force in late 2014, and the "sakigake" system of expedited reviews for pioneering therapies.
This has already led to the other iPSC study approvals, which have included small-scale clinical research on iPSC-derived retinal cells for age-related macular degeneration, neuronal regeneration in Parkinson's disease, and planned studies for corneal and cardiac tissue regeneration.
More controversially, this environment in late December resulted in the first marketing approval globally for a stem cell-based therapy in spinal cord injury, Nipro's Stemirac. The conditional clearance by the health ministry came after an expedited review.
In that case, the therapy involved the cultivation and intravenous re-injection of mesenchymal stem cells derived from patients' own bone marrow, within several months of the initial injury.
But the allowance of broader commercial use - potentially under reimbursement by Japan's national health insurance system - generated scrutiny and some criticism from cell therapy experts around the world. The main concern was that it was granted on the basis of a 13-patient, non-double-blinded trial, no detailed results from which have yet been peer reviewed or published.
Researchers maintained in summary results that there was improved motor function in some cases, while risks, safety and efficacy in wider use will be closely followed up in a post-approval all-patient monitoring program under the conditional approval.
Nevertheless, one US researcher described the decision as "an unfortunate step away" from cumulative experience in valid clinical practice. (Also see "Surprising SanBio/Sumitomo Stroke Stumble Slams Stocks " - Scrip, 31 Jan, 2019.)
Whatever the risks, researchers and regulators in Japan apparently see these worth taking given the clear medical need in a highly debilitating and usually untreatable condition. Serious spinal cord injuries are estimated to affect around 5,000 people annually, and around 100,000 in total, in the country.
From the editors of PharmAsia News.