June 1, 2020

The Niche

Knoepfler lab stem cell blog

Japan stem cell oversight system too lax?

The HeartSheet product shown here is advancing in the pipeline rapidly in part due to the Japan system of conditional approval of stem cells
The HeartSheet product shown here is advancing in the pipeline rapidly in part due to the Japan system of conditional approval of stem cells

The Japan stem cell and regenerative medicine oversight system has been designed to move investigational therapies forward fast, much faster than the systems in other countries such as the U.S. But how well is it working so far?

It’s an important question both for that country and more globally as the Japanese system was touted by some as a model and a reason why the U.S., to remain more competitive in this industry. Some of the same folks felt that the U.S. should also adopt a conditional approval approach and lobbied in past years for the REGROW Act. I felt REGROW was an extremely risky piece of legislation, especially in its initial incarnations. The regenerative medicine provisions in the 21st Century Cures Act, which became law, were more measured and balanced. We’ll see how it turns out now that it is being implemented in a practical sense in the real world. In the mean time, some of us have continuing concerns that the oversight system for stem cells and regenerative medicine in Japan may be too permissive.

Within the Japanese regenerative medicine oversight system, clinical studies involving induced pluripotent stem (IPS) cells such as the one I blogged about last week for heart disease involving the so-called HeartSheet led by Yoshiki Sawa can take steps forward with less pre-clinical and/or early clinical trial data than one might expect. The news about the heart IPS cell study has generated both buzz and some criticism that it is too risky.

The critics include Nature, which in an editorial this week called for better oversight in Japan and more preliminary data before stem cell therapies are sold to patients. The editorial was subtitled strongly, “Japan needs to demonstrate that a promising therapy for damaged hearts works as claimed.” Also, the editors wrote (emphasis mine), “The government needs to move quickly to make sure that evaluation of the HeartSheet therapy is as rigorous as promised. As more treatments emerge, officials should make sure that — fast track or not — they have a valid claim to efficacy before being sold to patients.

A NatureNews piece by David Cyranoski also highlighted some concerns about this situation:

“Yoshiki Yui, a cardiologist at Japan’s Kyoto University, says that, as well as meeting the requirements for safety, researchers should show that their treatment is effective, which would require testing it in larger numbers of people than are currently required. The evaluation process should also use randomized, controlled clinical trials, the gold standard for demonstrating efficacy in medical research, he says.

The iPS-cell therapy has potential, Yui adds, but under the current approval system, “we won’t know if it works or not” because it won’t have been tested in a controlled trial. “The biggest problem is there’s no adequate system of evaluation in Japan,” says Yui.”

The Japanese government contends the current system is fine. You can see more about Yui’s concerns including from a medical science level in a piece here.

It seems to me that it is only logical that stronger proof of efficacy including data from rigorously designed studies with proper control subjects is needed at the pre-market step. Less data equals higher risk for patients even if it also means speedier clinical science progression, but the question is where is the sweet “speed” spot of risk versus potential benefit? My own view is that Japan is still somewhat leaning too far to the speedy side at the moment. That could change.

Meanwhile, stem cell oversight is evolving in interesting ways elsewhere across the globe too. For instance, here in the U.S. we have the regenerative medicine advanced therapy (RMAT) designation program, which is also a regulatory experiment in accelerating stem cell oversight but does not allow selling incompletely tested stem cell therapies to patients, and also this week we have the new Right-To-Try law that may impact the stem cell field potentially interfering with some elements of oversight.

More will be coming on Right-To-Try and stem cells in future posts.

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