With 21st Century Cures Act, the future of regenerative medicine is 'inject and see'

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If Sammy Jo Wilkinson had a spirit animal, it would be Marty McFly. For the past four years, the 51-year-old California resident has been using stem cell therapy to beat her secondary progressive multiple sclerosis back into remission. Gone is the paralysis to the left side of her face and the numbness in her fingers. In February, she walked for the first time in years. “I’m living in a future that everybody will have some day,” says Wilkinson, who co-founded the patient’s rights group Patients for Stem Cells. “We’re trying to tell everybody the solution is here now, we just need a logical way to bring this to patients sooner rather than later.”

According to Congress, that logical way is the 21st Century Cures Act, a labyrinthine bill that would make the most significant changes in decades to how medical treatments are tested and brought to market. Politicians are working overtime to pass it before the new year— it’s the number one priority for the lame duck session, passing the House on Nov. 30 and advancing through the Senate last night. Final passage is expected to follow later this week.

In some ways, the legislation lives up to its name: It includes ambitious goals to advance biomedical science, and will inject $4.8 billion into a long-stagnating National Institute of Health budget. But attached to those promises is a roadmap for abandoning the gold standard of medicine in favor of an expedited “middle path” for drugs, medical devices, and regenerative therapies. Critics say it’s deregulation in sheep’s clothing— and worry that both science and patients are going to suffer.

Whether you applaud or decry the legislation, it’s almost certain to pass and be signed into law, if not by President Obama, then by the incoming administration. Which means regenerative medicine is headed for prime time. Welcome to the era of “inject and see.”

Medicine’s Wild West

In 2012, Wilkinson flew to Houston to receive her first stem cell treatment at Celltex Therapeutics. Technicians there extracted adult stem cells from her fat tissue, then cultured them for 13 days, allowing the population to expand before injecting the cells back into Wilkinson. The effects, she says, were immediate. She had less pain, more energy. But a few months later, the Food and Drug Administration (FDA) ruled that Celltex was violating a 2006 rule change that allowed the FDA to regulate expanded cell populations as drugs. They would need to get agency approval before being used in treatments.

These actions became the most visible confrontation in a bitter, decade-long battle between regulators and patients regarding the legality of regenerative therapies. While some companies, like Celltex, moved their operations to Mexico to skirt regulations, other small clinics with lower profiles rushed to fill the void. The FDA has been slow to investigate the proliferation of these clinics and the therapies they market. Today there are close to 600 businesses in America selling stem cell solutions for everything from deafness to Alzheimer’s and autism, all without FDA approval, according to a study published in February by Paul Knoepfler and Leigh Turner.

Turner, who is a bioethicist at the University of Minnesota, was surprised by the scale of exploitative behavior he found. “Anyone can buy a domain name and create a website and make grandiose therapeutic claims that have no basis in reality whatsoever,” he says. The situation has prompted scientists and policy wonks to dub stem cell clinics “medicine’s wild west.” The 21st Century Cures Act will change that—not by reining in unproven, unregulated treatments, but by providing a direct path to medical acceptance. Under the act, the FDA would have the authority to grant accelerated approval for regenerative medicines, skipping straight from animal models and safety trials, over efficacy testing in humans, to post-market review. The new laws would also compel the FDA to update its regulations for such products.

That, Turner says, could be a disaster for traditional stem cell research. “If you legitimize these therapies and allow businesses to commercialize them, then it becomes difficult to recruit individuals for actual phase 3 clinical trials,” he says. Clinical trials have guidelines about who can and can’t participate— these inclusion/exclusion criteria helps to produce reliable results. People who go onto the marketplace and get an unapproved therapy won’t be able to participate because their inclusion criteria becomes compromised. “They’ll be lost to science,” says Turner.

The Dark Echo

Knoepfler, who is a stem cell researcher at UC Davis, is worried about an even more troubling outcome: What happens once people get hurt by these therapies, either physically or financially? Phase 3 studies typically include a much larger number of participants to enable statistical assessment of clinical benefit and detection of any unusual risks not discovered in smaller studies. Eschewing this step places those risks and uncertainties squarely on the shoulders of paying patients. Because treatments aren’t covered by public or private insurers, patients can spend a fortune in their quest for a cure (Wilkinson has spent $90,000 out of pocket). Or worse, develop a tumor, go blind, or have a stroke and die.

“I think we’re going to hear a lot more about that in the next few years,” says Knoepfler. Which is unfortunate timing, since that’s when he expects real, rigorously tested therapies to be coming online. Stem cell treatments that help diabetics grow new insulin-making pancreatic cells, halt the progression of ALS, and strengthen cardiac muscle cells in people suffering from heart failure are just some of the therapies advancing steadily down the full clinical trial pathway. “There’s real hope, he says. “And my worry is that the dark echo of the clinics will negatively impact the perception of the whole stem cell arena.”

But people like Wilkinson don’t have that kind of time. “Facebook is more like an obituary page some days, and I’m just tired of watching my friends die,” she says. Her organization was instrumental in getting a record number of comments during the FDA’s public hearings on draft guidances for stem cell therapies in September. She says she’s not paid by Celltex or anyone else to be a voice for the technology, and really just wants the FDA to stop telling her what she can and can’t do with her own cells.

Not so fast

While patients and regenerative medicine investors celebrate and researchers raise alarms, top FDA officials are holding their ground. In an article published in the New England Journal of Medicine last Wednesday, FDA Commissioner Robert Califf expressed skepticism about the safety and efficacy of stem cell treatments. “The current excitement over the potential for stem cell therapy to improve patient outcomes even cure disease is understandable,” he wrote. “However, to ensure that this emerging field fulfills its potential promise to patients, we must first understand its risk and benefits and develop therapeutic approaches based on sound science.”

The timing of the article suggests the FDA won’t be wielding its authority to accelerate approvals any time soon. Won’t, or perhaps can’t. The 21st Century Cures Act doesn’t exactly spell out how it will provide the necessary resources to implement all that it asks of the agency. Currently, strict conflict of interest rules and a draconian hiring process hinders the agency’s ability to attract top talent. “The FDA has had a hiring shortage problem for over a decade,” says David Gortler, a former FDA senior medical officer. He says there are small ways to speed up the review process here and there, but nothing on the scale people are imagining. “Mark my words. Nothing will happen,” he says.

If so, the agency will be living up to its reputation as a creaking thorn in the side of forward progress. But according to Turner, the FDA is just a convenient scapegoat. The real thorn is simply the reality of being human. ‘We’re trying to develop truly safe and efficacious cell based therapies for what throughout human history have been intractable diseases,” he says. “Human biology is the challenge, not bureaucratic inertia.”

And not even a plutonium-charged Delorean can change that.