Companies are skirting regulation to be the first to build the next big stem cell therapy, creating clinical concerns and poor patient outcomes.
Physicians are paying close attention to a disconcerting trend in medicine, wherein companies are exploiting loopholes in the US Food and Drug Administration’s (FDA) regulatory pathway so they can market unapproved stem-cell treatments directly to consumers.
The unapproved treatments are not formulated in a controlled setting, and as a result, often lead to poor health outcomes, according to Thomas A Albini, MD (pictured), associate professor of Clinical Ophthalmology at the Bascom Palmer Eye Institute, University of Miami Health System.
“This loophole is what’s giving companies the go-ahead to really start a tremendous industry. It’s now estimated to be a $2.4 billion per year industry, involving about 60,000 patients, where patients are paying up to $40,000 out of pocket per procedure to try and fight a number of diseases,” Albini said at the annual meeting of the American Society of Retina Specialists (ASRS) in Boston. “These are not FDA approved treatments that are being provided.”
Companies in the unapproved stem-cell treatment space claim to offer solutions to a wide breadth of common ailments and conditions, Albini said, but are most active in orthopedics, with other areas of study like ophthalmology and neurology gaining traction as well.
“There’s a lot of focus on diseases in spaces where patients are frustrated with currently available therapies, like dry macular degeneration and wet macular degeneration. For example, we now have stem cell eye drops for macular degeneration,” Albini said, clarifying that the eye drops are an untested treatment. “There’s all kinds of things on the market, and none of them are well-studied.”
Albini and colleagues are working to change that fact, and started by examining 3 patients who presented in hospital emergency rooms shortly after receiving unapproved stem cell treatments for ophthalmic diseases. All 3 patients suffered bilateral vision loss after receiving bilateral intravitreal injections of stem cells at clinics that had no association with medical centers.
Each patient received 0.1 ccs of autologous adipose tissue derived from stem cells, harvested the same day as the injection. They paid $5,000 for the procedure, and were under the impression they had met inclusion and exclusion criteria to participate in a clinical trial.
However, according to Paul Sieving, MD, Director of the National Institutes of Health’s (NIH) National Eye Institute (NEI), the trial was far from clinical in nature.
“These are not trials. Trials consist of scientific research that has a hypothesis, has a methodology, collects data in a systematic way, and analyzes that data. None of that is occurring in these trials,” he said. “I would congratulate the ASRS for bringing this to the attention of the American people and to medicine. In the NIH, we use the information developed by the ASRS in beginning to formulate policy.”
There was no data and safety monitoring committee, Sieving said, adding that the FDA was not aware that the procedures were happening, and an American licensed physician was not involved directly in the injection procedures — they were provided by a nurse practitioner with apparent lack of adherence to protocol.
The first patient in Albini’s study of the dubious stem cell trials was a 78-year-old female with a history of neovascular age related macular degeneration (nAMD). She had previously received multiple anti-VEGF injections in both eyes.
“Her vision had gotten to the point that she was having difficulty driving, so her family looked online to see what other therapies were available, and this is what they found,” Albini said.
After receiving stem cell injections intravitreously, the patient presented with poor vision in both eyes, diffused hemorrhagic retinopathy, and tissue injected into the vitreous cavities of her eyes.
“She says that the injection was very painful. She lost vision with the first day following the injections in both eyes,” Albini said. “She went on to develop delayed retinal attachments at day 16 and 38.”
Albini’s second patient was a 72-year-old female who presented in the emergency room with pain and extremely elevated pressure in both eyes. Her pre-procedure vision was 20/60 in her right eye and 20/30 in her left.
“When she came in she had displacement of her crystalline lens and it seemed like all the zonules had been broken. We hypothesized that this could’ve been from some of the enzymes that are used in the preparation of these stem cells — that they may not have been adequately washed out,” he said. “There was vitreous debris in the posterior segment, so she underwent emergent bilateral vitrectomies to remove the lenses.”
The patient also had retinal detachment in her right eye and silicon oil in both eyes, he added.
A third patient — an 88-year-old female – had preoperative vision of 20/40, 20/200, and presented 7 days after receiving stem cell injections.
“Initially the left eye did not look bad, but ultimately she developed retinal detachments in both eyes,” Albini said.
All told, 5 out of the 6 eyes studied had retinal detachments, and many had retinal hemorrhaging, luxation of the lens and weakness of the zonules.
“The outcomes were dismal compared with the preoperative visual scores,” he said.
The big takeaway for Albini is not that stem cell therapies are to be avoided — in fact, it’s quite the contrary.
“Stem cell treatments in ophthalmic disorders have great potential, but clearly, the isolation and delivery methods are non-trivial and need to be worked out,” he said. “It’s very dangerous to have these therapies marketed direct to the consumer without any regulation.”
Wiley Chambers, MD, deputy director of the FDA's Divison of Transplant & Ophthalmology Products Center for Drug Evaluation & Research, said that the agency needs help in identifying dubious stem cell therapy marketing efforts, to gather more information and potentially push the therapies in a more clinical direction.
"We do think that [stem cell therapies] are a potential treatment form which have a great deal of potential to help sight, but we think it needs to be in a controlled setting," he said. "If you are aware of these types of treatments — and I use that term loosely – please let the FDA know."