n both coasts, campaigns are building to get desperate patients faster access to stem cell treatments — in some cases, before they are proven to work. And that is making some scientists nervous.
In Washington, a US senator recently introduced a bill that would allow the Food and Drug Administration to grant conditional approval to stem cell treatments without data from the big Phase 3 trials usually required before a drug hits the market. In California, meanwhile, the state stem cell agency is enlisting patients to back an aggressive push to speed up the federal regulatory process for stem cell therapies.
Proponents say an accelerated regulatory process will help patients, but a chorus of critics warn that faster approvals could undermine the FDA’s authority to ensure that only rigorously tested therapies make it to market. They point to the hundreds of largely unregulated “stem cell clinics” hawking unproven treatments for everything from autism to heart failure and warn that hucksters will be emboldened if FDA regulations on the stem cell field are relaxed.
“There’s a risk that the dominant narrative, not just amongst the clinics, but in the broader field, becomes, ‘Hey, the FDA system is the problem. We need to weaken [regulation] to move forward,’” said Paul Knoepfler, a stem cell researcher at the University of California, Davis.
Good science and effective treatments take a long time, said Timothy Caulfield, a health policy expert at the University of Alberta. And with their lobbying, stem cell boosters appear to be trying to “will the science into existence,” he said.
“There is exciting work being done, slowly making its way through clinical trials,” Caulfield said. But as of now, he said, “it’s just not there.”
Treatments hiding in belly fat?
Stem cells can be found in tissues from belly fat to bone marrow and are notable because they’re so flexible; they can develop into many different cell types. Doctors believe they have the potential to replace damaged or dead cells throughout the body.
In recent weeks, researchers have reported using stem cells to help stroke victims regain some movement and to close a hole in a woman’s airway, although they can’t say for sure if the stem cells were responsible for the improvements. In these cases, doctors often apply to use experimental stem cell therapies under what’s known as the FDA’s compassionate-use program.
But for every story that encourages the medical community comes a tale like the one that doctors reported last week of a stroke patient who went abroad for stem cell treatments and came back with a growth in his back and more extensive paralysis.
“At this time, the value of stem cells as a treatment for most conditions is largely unproven and more information is needed about their potential benefits,” the FDA said in a statement.
Most experts agree that the government should crack down on clinics selling unproven stem cell “treatments” directly to the public. And most agree that the FDA could streamline the process of approving legitimate stem cell treatments. Such treatments take, on average, more than twice as long as standard drugs to move from discovery to clinical trials, in part because of how long it takes for the FDA to grant approval for testing in humans.
But beyond those two goals, the stem cell community is fractured.
Pushing for speedier approvals
In March, Senator Mark Kirk (R-Ill.) introduced the Regrow Act, the measure that would allow the FDA to bring drugs to the market for five years without Phase 3 trials. Phase 3 studies are meant to determine whether treatments actually work, and many promising therapies fail at this stage.
Supporters in no way want shoddy treatments to gain conditional approval, but say patients deserve access to treatments that have shown promising results in early clinical studies.
“By expanding options for those living with Alzheimer’s, Parkinson’s, diabetes, and stroke, we can help more patients live the life they want on their own terms,” Kirk, who suffered a stroke in 2012, said when he introduced the legislation.
The bill, which has also been introduced in the House, has bipartisan sponsors and would effectively match the regulatory framework in Japan, considered a leader in the stem cell field. The Regrow Act could get absorbed into broader legislation called the 21st Century Cures Act, which aims to speed FDA approval of drugs and devices.
The measure has drawn the support of some stem cell companies, patient groups, and researchers; advocates for cerebral palsy patients, for example, wrote in letters to Congress that the bill could allow patients to “experience the most promising areas for groundbreaking treatments.”
Dr. Charles Murry, the interim director of the University of Washington Institute for Stem Cell and Regenerative Medicine, said the institute supported the measure because it could lead to treatments “for today’s patients.” He noted that Phase 3 trials would be conducted during the conditional approval period, so any treatment could be pulled from the market if it’s shown not to work.
“An attempt to accelerate therapies can increase the likelihood of complications from these therapies,” Murry said. “On the other hand, working slowly, while less risky, results in more people suffering from potentially treatable conditions. The goal will be to strike the right balance.”
Supporters also point out that the FDA already has the authority to give approval — without Phase 3 studies — to drugs in some cases, such as those treating rare diseases.
A warning of ‘grave consequences’
But a number of industry groups, scientists, and patient advocates have come out strongly against the bill. They say that data from Phase 1 and Phase 2 studies do not give the full picture of a drug’s impact; dangerous side effects might not emerge until a larger number of patients are treated in Phase 3 trials.
Both the International Society for Stem Cell Research and Alliance for Regenerative Medicine oppose the measure. So does a coalition of advocacy groups — including the National Organization for Rare Disorders, the Cystic Fibrosis Foundation, and the Michael J. Fox Foundation for Parkinson’s Research — that told Kirk in a letter the bill “may result in grave consequences for patients.”
“We just don’t think that patients or health care providers should have to pay for therapies whose efficacy has not been established,” said Sean Morrison, the president of the international research society.
Another concern: Shady operators may flood the FDA with applications for conditional approval, hoping to gain a glint of legitimacy.
“What worries me … is that the FDA is going to be clogged with something like a ratio of 500 to 1 really bad ideas to really good ideas,” said Jeanne Loring, the director of the Center for Regenerative Medicine at the Scripps Research Institute.
The debate over the Regrow Act echoes other fights about how tightly the FDA should scrutinize drugs and devices. Families of children with the fatal disease Duchenne muscular dystrophy, for instance, have been lobbying the FDA to approve a drug despite slim data about its efficacy.
“There’s this misperception about why these trial requirements exist,” said Dr. Aaron Kesselheim, an expert on regulatory issues at Brigham and Women’s Hospital and associate professor at Harvard Medical School. “This isn’t like a capricious way of trying to delay getting products on the market. Clinicians need data to guide their decision making, and patients want treatments that work.”
A fight brews in California
Another debate is brewing in California, where the California Institute for Regenerative Medicine — the state stem cell agency established by voters in 2004 — has been increasing its advocacy for speedier development of stem cell therapies.
Randal Mills, who became CIRM’s president in 2014, has been calling on the FDA to review its regulations and adopt a more efficient process for approving clinical trials and treatments. Patients are tired of waiting for researchers and regulators to get them the stem cell treatments they have been hearing so much about, Mills has said.
CIRM is not suggesting specific policy changes, and it is also not taking a position on the Regrow Act, Mills said in an interview. But he noted that the FDA already expedites approval of certain drugs.
The regulatory landscape “creates uncertainty, and that uncertainty stops innovation,” Mills said. “The system just needs to be looked at again.”
Mills said that researchers share some responsibility for advancing the field. CIRM, which has funding to last through 2020, wants to triple the number of clinical trials it sponsors and invest in more basic research to fill the pipeline of therapies that could make it to human testing. The agency is also launching new centers to help scientists navigate the FDA bureaucracy.
But CIRM’s activism around the FDA has rubbed some California stem cell researchers the wrong way, including scientists who have received funding from the agency and who typically support the institute.
In a recent op-ed in the San Francisco Chronicle, Knoepfler wrote that “such politicking risks doing much more harm than good” and that with continued lobbying, “politics may vie with biomedical science in guiding its decisions.”
Loring echoed that concern about CIRM’s advocacy: “I think it’s too public, and I think it risks some blowback,” she said. “The attitude that I think we should all have, although unfortunately it’s broken down, is that the FDA exists to help us.”
That view is not universal among stem cell researchers in California. Several scientists told STAT that CIRM focuses more now on translating research into marketable therapies, but said they have not seen any untoward political advocacy.
In the interview, Mills strongly denied that he is anti-FDA or antiregulation. He said critics were reading too much into his call for the agency to revisit its rules.
“I’m not married to a solution, but I’m not going to ignore that there’s a problem,” Mills said. “That’s not an extreme position.”