Regenerative & Cell-Based Medicine: July 2021

Ellen Drage O’Reilly

June 24, 2021 (Axios.com) — An industry centered around unproven stem cell therapies is flourishing due to misinformation.

Why it matters: Stem cells offer a tantalizing potential to address a large number of diseases, like Parkinson’s, ALS, cancers and bodily injuries. But only a small number of therapies have been found safe and effective through clinical trials, while misinformation continues to proliferate.

• Not only are people sometimes losing tens of thousands of dollars for unproven therapies, but some have reported suffering permanent damage like blindness, pulmonary embolism or tumor growth, says Leigh Turner, associate professor at the University of Minnesota’s Center for Bioethics.
• Using unproven therapies may also exclude people from clinical trials, causing them to lose that potential treatment option, as well as damaging scientific discoveries by limiting trial participants, Turner adds.

The latest: The Pew Charitable Trusts issued a brief in early June that describes a rising number of reported adverse events.

• There are more than 700 U.S. clinics offering unapproved stem cell and regenerative medicine interventions for conditions such as Alzheimer’s disease, muscular dystrophy, autism, spinal cord injuries and even COVID-19, Pew reports.

Background: Clinics with unregulated stem cell products or therapies began emerging in the early 2000s all over the world, “taking advantage of the media hype around stem cells and patients’ hope and desperation,” says Mohamed Abou-el-Enein, executive director of the Joint USC/CHLA Cell Therapy Program at USC’s Keck School of Medicine.

• “There is an infodemic in this area; it’s run by misinformation,” says Zubin Master, associate professor of biomedical ethics at Mayo Clinic’s Biomedical Ethics Research Program and the Center for Regenerative Medicine.
• He points to a growing practice of using “tokens of legitimacy,” where clinics try to fully legitimize their practices by having prestigious scientists on their boards or showcase figures from pay-to-participate trials, which have their own ethical dilemmas.

Regulatory agencies like the FDA need to crack down on these misinformation campaigns, several experts say.

• The FDA established a regenerative medicine policy framework in November 2017, but it gave a long “discretion” period of three years that was extended another half year due to the pandemic, to May 31. The agency currently has only a short list of approved cellular and gene therapy products.
• Peter Marks, director of FDA’s Center for Biologics Evaluation and Research, tells Axios the “compliance and enforcement discretion policy was never intended to excuse the violations of manufacturers or health care providers offering unapproved regenerative medicine products that have the potential to put patients at significant risk.”
• “During that three and a half year period, we did take compliance and enforcement actions to protect the public health,” Marks said in an email. Some believe the FDA will crack down now that the discretion period is over.

What they’re saying: Turner says in that period the FDA contacted about 400 businesses to warn of noncompliance and issued several warning letters, but adds that was “probably of very little consequence. … A one-year period could be justified, but three years is basically like a security guard walking away from the post, and you can guess what’s going to happen.”

• Abou-el-Enein says, “I think FDA has established an excellent regulatory system for cell therapy development … [but] it is understandably challenging to keep the regulations up to speed.”

The big picture: This is a global threat as well, Master and Abou-el-Enein say. In a recent perspective in the journal Stem Cell Reports, they argue for the WHO to establish an expert advisory committee to explore global standards.

• “We need to devise new approaches to rally governments, regulators, and local communities to support the growing efforts to curb the spread of unproven SCIs,” or stem cell interventions, Abou-el-Enein says.
• The 2021 guidelines from the International Society for Stem Cell Research have also stressed the need for standards, they say.

What’s next: Researchers are still hopeful stem cell therapies can be effective but emphasize the need for more research into how stem cells work and how they can be manipulated for therapies.

• There have been some promising results from cell-based therapy R&D via academic and biotech firms that either has or is currently undergoing proper clinical testing protocols, Abou-el-Enein says, pointing to the EU’s authorization of a treatment for Crohn’s disease called Alofisel and Holocar for corneal ulcers.
• “We’ve seen improbable advances in the field of cell-based regenerative medicine that show great promise. The advances in cell-based gene therapy indicate what may be possible, as evidenced by the five FDA-approved chimeric antigen receptor-T cell therapies,” Marks says.