The phase I trial of a once-controversial clinical trial testing the effects on type one diabetes of a 94-year-old drug used to combat tuberculosis was so successful that in June of this year, the FDA approved the research to expand into a second phase of the trial.
“The data went further than we expected,” Dr. Denise Faustman, Director of the Immunobiology Laboratory at the Massachusetts General Hospital and an Associate Professor of Medicine at Harvard Medical School, says about the first phase of the trial, which was concluded in 2012. “It was supposed to be a safety trial to see biomarker changes, but the results we produced went beyond that.”
The results of the test on Bacillus Calmette-Guérin, or BCG, did in fact show it was safe to use on type 1 diabetics. But, because of the widespread use of the generic drug for so many years, that was expected. But the small doses of BCG administered to as two vaccines in three subjects followed for 2 years compared to 97 placebo and untreated reference subjects revealed the specific death of so called “bad” T cells that attack and kill insulin-producing islet cells. Additionally, the subjects, who had diabetes for 15 years or more, showed a “transient increase in/restoration of pancreatic insulin secretion after BCG vaccination,” according to Faustman and the peer reviewed published data.
For phase II 150 subjects with type one diabetes for 15 or even 20 years who do not suffer from any diabetic complications (such as neuropathy, retinopathy, and others) will be tested for five years to determine the dose, and frequency of dosages, required to potentially reverse type 1 diabetes, Faustman said. The subjects, aged 18 to 60, must have low but still detectable levels of insulin production. The protocol for the trial stipulates that the subjects will receive two injections, four weeks apart, of either BCG or a placebo, along with annual injections of either over the next four years.
Faustman says that her work has raised the ire of some scientists and organizations for two reasons: It runs counter to the prevailing research emphasis to either prevent type 1 diabetes, or reverse it in people who have been recently diagnosed with diabetes and, at the time, ran into a stiff political headwind from embryonic stem cell researchers. The irony, Faustman says, is that ten years later most of the scientific questions argued about then have been resolved and are now more mainsteam concepts.
“Pharmaceutical companies can’t invest in generic drugs. They love the science and the pathway, but there is no business model they can pursue and be responsible to their shareholders” Faustman said. “But, because it’s a 100-year-old drug that’s not proprietary we have the option to deliver a very affordable treatment, that would be accessible for everyone.”
Additionally, Faustman states that funding has been difficult to come by because her research is unconventional in many respects. One example, she says, is that she is studying reversing diabetes in people who have had the condition for decades and not merely a few years.
“Most, is not all, immune intervention trials have kids or the recently diagnosed as subjects,” Faustman says. “That’s mainly because they are still producing some insulin.”
Faustman says that she is testing subjects with long-term diabetes not only because she considers them “needy and deserving,” but because it’s considerably less expensive to test on subjects who have had diabetes longer. She says to recruit and test newly diagnosed diabetics might cost up to $1 billion. She, on the other hand has budgeted $25 million to complete phase two of her trial, much of which has come from the Iacocca Family Foundation, which was established by Lee Iacocca after his wife died from complications of type one diabetes.
Despite the doubt surrounding her research, Faustman says the march of scientific progress has proved too much for the FDA and others to ignore. She says that BCG is now being tested around the world to treat other autoimmune conditions, including multiple sclerosis, Crohn’s disease, lupus, scleroderma and Sjögren’s syndrome and it’s credibility as a possible treatment for a host of conditions has grown.
“There is a renewed interest in BCG and, because of that, there is a renewed possibility we might make a breakthrough in reversing type one diabetes,” Faustman says.