Already troubled by the murky oversight of the rapidly expanding U.S. direct-to-consumer marketplace of unapproved stem cell therapies, bioethicists are now raising concerns about a new pathway that at least one company is taking to sell those products — the Right to Try Act.
The law, adopted in May 2018, allows critically ill patients to sidestep the U.S. Food and Drug Administration in seeking access to experimental therapies.
The growing unapproved stem cell market combined with the congressionally mandated laissez-faire approach for Right to Try, or RTT, could expose vulnerable patients to harm, bioethicists told S&P Global Market Intelligence.
Leigh Turner, associate professor at the University of Minnesota Center for Bioethics, has tried since 2013 to get the FDA to investigate one company, MD Stem Cells, for marketing to and treating U.S. patients with unapproved stem cell-based therapies.
Some patients have said the company's treatments have harmed them, leaving them with severe vision loss or even blindness, Turner told S&P Global Market Intelligence. He noted that a 2017 BBC investigation verified a number of those claims about MD Stem Cells and its experimental treatment.
MD Stem Cells continues to offer its unapproved stem cell treatment, which is derived from a patient's own bone marrow cells, in what the company calls clinical studies. To conduct such a study, a company would need to have an FDA-authorized investigational new drug application, or IND, and it is unclear if MD Stem Cells holds such an authorization.
Elsie Johnson, who has amyotrophic lateral sclerosis, has contacted the company asking for verification of its IND, but MD Stem Cells has not provided it.
Patients should be able to find out from the company if the product is under an IND, and those entities "should hopefully be able to truthfully answer that," said Peter Marks, director of the FDA's Center for Biologics Evaluation and Research.
"If it's a stem cell product, it should be under IND with the agency," Marks told S&P Global Market Intelligence. "If it's not, that's probably a red flag. It doesn't absolutely mean there's something wrong. But it may mean there's something wrong."
MD Stem Cells is run by a pair of ophthalmologists, but it offers stem cell programs for a range of complex conditions, including nervous system and neurological diseases.
The FDA declined to comment on whether it was investigating MD Stem Cells. The company declined to talk to S&P Global Market Intelligence about its business.
But Johnson and another patient with ALS, who asked to remain anonymous, have provided S&P Global Market Intelligence with details about their experiences with MD Stem Cells and its RTT program.
One way companies like MD Stem Cells solicit patients is by listing their treatments as studies on the U.S. government's clinicaltrials.gov website, run by the National Institutes of Health, Turner said.
The NIH does not verify companies that register on the site, nor does it monitor them.
Now, MD Stem Cells is using relaxed regulation under the RTT as a way to recruit patients with ALS. Also known as Lou Gehrig's disease, ALS is a progressive neurodegenerative condition that has no cure.
According to documents provided by Johnson and the other ALS patient, MD Stem Cells is getting recruitment help from an RTT-focused contract research organization operated by Richard Garr.
Garr recently changed the name of his company from Beacon of Hope CRO to Access Hope CRO after S&P Global Market Intelligence reported that an identically named company existed. The other Beacon of Hope CRO is part of Beacon Pharmaceutical and its venture arm Beacon Capital LLC, which is also affiliated with RTT and plans to set up a life sciences center in Jupiter, Fla.
Philippe Gastone, CEO of Beacon Pharmaceutical, told S&P Global Market Intelligence that Garr was a "former associate." Garr has repeatedly denied any connection and told S&P Global Market Intelligence that he was not pressured to change his company's name.
Both Garr's and Gastone's companies are in South Florida's Palm Beach County. MD Stem Cells runs clinics in nearby Broward County, though it lists Westport, Conn., as its headquarters.
RTT business model
On Garr's Access Hope CRO website, the company states it is the "first CRO founded exclusively to facilitate Right to Try treatment programs at scale for the biopharmaceutical industry."
"We can design, recruit and manage sites and patients for Right to Try-compliant expanded-access treatment programs under the new Right to Try legislation," the company said, emphasizing its electronic case report form system.
Garr played an early role in getting RTT through the Republican-controlled Congress in 2018, testifying on Capitol Hill to urge lawmakers to adopt it.
Critics such as Turner have said the real intent of RTT was to weaken the FDA. They have raised concerns that patients could be harmed by companies seeking to profit from unproven therapies for serious diseases for which no treatments have been approved.
RTT proponents, including President Donald Trump, say the FDA's decades-old expanded-access program was not moving fast enough to give patients access to experimental treatments. Under that program, also known as compassionate use, regulators have granted 99% of requests to access experimental treatments.
Brainstorm Cell Therapeutics Inc. has permitted a single patient, Matt Bellina, to use its experimental ALS therapy NurOwn under RTT, while Epitopoietic Research Corp. provided its investigational glioblastoma treatment Gliovac to an unidentified patient in 2018 under the federal law.
ERC has since approved a handful of other RTT requests for Gliovac, Joseph Elliot, managing director for ERC-USA, told S&P Global Market Intelligence.
Elliot confirmed his company is offering Gliovac in a pay-to-participate RTT program. Brainstorm's CEO covered Bellina's costs.
No major biopharmaceutical company has publicly offered their experimental therapies under RTT, Turner said.
In a Sept. 5 article in the peer-reviewed scientific journal Cell Stem Cell, Turner and his coauthors identified a number of stem cell companies that were invoking RTT in providing unapproved products to seriously ill patients — and charging them for it.
Like ERC, MD Stem Cells' RTT program is pay to participate. In most clinical trials, patients are not charged to participate, Turner said. Federal regulations permit sponsors of clinical trials involving an FDA-authorized IND to recover certain costs related to the studies, he noted, and the agency must approve those charges.
MD Stem Cells told Johnson the company's RTT treatment was $19,600, though she could get the same procedure through the clinic at $14,500 under its Neurological Stem Cell Treatment Study. The RTT's greater costs were due to longer follow-up — multiple years versus one year for NEST. Garr told the other patient the RTT treatment cost $20,000 overall.
In its communications with Johnson, MD Stem Cells said its RTT program was being coordinated by its partner, Garr's CRO, and would only involve ALS patients.
Right to Try requirements
Under RTT, a patient's physician can request access to experimental treatments from drugmakers after a phase 1 safety study is completed and during or after a phase 2 or 3 efficacy trial. The therapy must be under an active FDA-authorized IND.
Turner said he did not find any evidence that MD Stem Cells' therapy meets the RTT criteria.
In responding to questions about whether MD Stem Cells holds an IND and meets the RTT requirements, Garr said nothing in the law states that only the entity that produced the phase 1 results can provide the treatment to the physician who administers it to the patient.
In other words, he said, if one company was in a phase 2 trial with a drug, another company could treat a patient with that therapy under RTT.
Whether MD Stem Cells' program meets the RTT requirements "is irrelevant," Garr said, because it is the therapy and the patient that must meet the law's standards.
"It appears to me that he is advancing a misreading of the law and claiming that products can be administered on an RTT basis as long as someone, somewhere has completed a phase 1 study using that product," Turner said.
While the person administering the drug to the patient does not have to be the holder of the IND, the therapy must be the product that was studied in the phase 1 trial and covered by the IND to be eligible for RTT, Patti Zettler, assistant professor of law at The Ohio State University and a former FDA attorney, told S&P Global Market Intelligence.
The manufacturer or sponsor of the product retains various obligations under the law, like the reporting requirements, regardless of who is administering the drug, added Holly Fernandez Lynch, assistant professor of medical ethics at the University of Pennsylvania.
"When we're dealing with very ill and vulnerable patients, there is an extremely high bar to show that all parties are acting above board and in the best interest of these patients," said Jeremy Snyder, a professor and bioethicist at Canada's Simon Fraser University.
Onus on patients
Patients bear the burden of doing the due diligence to ensure that the product they are accessing meets the RTT criteria, according to the FDA's Marks.
FDA Center for Biologics Evaluation and Research Director Peter Marks
If stem cell companies are uncertain about whether they need an IND, Marks said they can obtain informal regulatory advice from the FDA's Tissue Reference Group Rapid Inquiry Program.
The FDA's bone marrow references on its stem cell website for patients, however, leave some ambiguity on the types of products that require INDs.
After repeated requests, the FDA declined to clarify the website's language.
Turner said he believed MD Stem Cells' therapy requires an IND.
Unfortunately, he said, ambiguous language on the FDA's website and the lack of screening by the NIH for clinicaltrials.gov leaves patients seeking treatments vulnerable to companies with treatments that could harm them.
"These businesses are adept at taking advantage of regulatory exceptions and gray zones where there is lingering uncertainty about whether FDA approval is required," Turner said. "The FDA needs to offer better guidance to patients considering entering the direct-to-consumer marketplace for supposed stem cell treatments. More importantly, the FDA needs to investigate and take action against far more of the businesses that are violating federal regulations and putting patients and public health at risk of harm."