Immunotherapy for Type 1 Diabetes
What is immunotherapy?
By definition, it is the treatment of a disease by targeting the immune system. Cancer, multiple sclerosis, rheumatoid arthritis and other conditions all represent targets of research exploring immune interventions.
And, yes—type 1 diabetes is on scientists’ radar for this type of treatment! The “autoimmune” label has been present since the 1970s, as the scientific community has increasingly accepted that the body’s T-cells destroy its own insulin-producing cells, thus resulting in type 1. However, decades of research have yielded more and more failed data. What lies ahead? Beyond Type 1 took a look at next steps for developments of immunotherapies for people living with type 1 diabetes.
A shift in perspective
“For a long time, everybody thought that type 1 would be cured by immunosuppression,” said The Faustman Lab’s Dr. Denise L. Faustman, M.D., Ph.D., but the past 30 years of discovery “have proven that immunostimulation is what’s needed.”
A main objective in seeking an immune intervention for people with type 1 diabetes is “getting the immune system restored,” continued Dr. Faustman, who is the director of the Immunobiology Laboratories at Massachusetts General Hospital in Boston, Massachusetts.
Over the last five years, the view of the scientific community on immunotherapies directed toward type 1 has dimmed with failed trial after failed trial, Dr. Faustman continued.
Among the challenges to conducting immunotherapy trials, as noted in a recent article in Pharmaceutical Journal, are the difficulty of securing buy-in from funders to conduct commercial and nonprofit trials, finding study participants with enough beta cell function to target with treatment and drawing those participants from the 5 percent of people with diabetes who have type 1. Researchers are looking for drugs that are safe to use in trials and that will also be approved by regulators.
“For 30 years, immune trials have been in pre-diabetics and new-onsets,” Dr. Faustman acknowledged. The added challenge has been, she noted, “Can we find something potent enough to treat the disease?”
New discoveries
The Faustman Lab’s trial has focused on the BCG vaccine, which has been used to prevent tuberculosis (according to Dr. Faustman the drug has been safely used in that capacity for over 100 years) and on an unusual patient population: people who are long past their type 1 diagnosis date.
Dr. Faustman’s team presented their eight-year-long study findings from a Phase I clinical trial at the ADA Scientific Sessions in June 2018. Here is a clip from the poster they submitted:
In a Phase I trial, BCG-treated subjects with type 1 diabetes (T1D) had statistically significant increases in regulatory T cell (Treg) numbers for four to six weeks after repeat BCG vaccination and > five year return of near normal blood sugars.
The findings, also published in Nature Vaccine, showed that, in Dr. Faustman’s words, “in long-term type 1 diabetic subjects we can restore blood sugars to near normal levels and these blood sugars are stable for the next five years without continuing interventions. These are the first immune intervention trials to work in long term diabetics and also show >five years of near normoglycemia.”
For more information about the ongoing BCG vaccine trial, read Curing Type 1 Diabetes: An Interview with Dr. Faustman.
The crux of The Faustman Lab’s research is that “nobody’s done this in people who’ve had Type 1 diabetes long-term,” added Dr. Faustman. “What’s beautiful about the BCG treatment is that it’s using limited dosing of a safe drug.”
Ongoing clinical trials
Dr. Faustman agreed that the reception to presenting her findings about this immunotherapy treatment at ADA was phenomenal. She is even more optimistic about managing the seven related trials currently underway.
“When there’s such a high failure rate, our data gives a major ray of hope that the right compound produces results,” she said, “I would like the therapeutic effect to kick in sooner, after year two or year one, and Phase III trials of BCG in patients with M.S. show a therapeutic effect in two years and the disease goes into remission and stays in remission beyond year five.
Other ongoing research includes a U.K. study of 27 recently diagnosed people with diabetes (PWDs) who take regular injections of autoantigens for a peptide immunotherapy. Novo Nordisk is conducting a Phase II trial that uses a beta-cell preservation approach with anti-IL-21 to target T cells.
A company called Caladrius is conducting a commercial Phase II effort involving Tregs called The Sanford Project: T-Rex Study. In March, Caladrius reported the study to be “non-futile” at the six-month point, after recent-onset participants had been injected with CLBS03, which the company calls “personalized autologous regulatory cell therapy.”
The conversation surrounding nonprofit studies vs. commercial studies and generic or open-label vs. brand-name therapies continues. Dr. Faustman thinks everything should be done with FDA supervision, and she encourages people with type 1 to visit ClinicalTrials.gov to see registered studies and get more information.
REFERENCES
American Diabetes Association: Type 1 diabetes
Caladrius: Press Release
Gale, Edwin A.M. The Discovery of Type 1 Diabetes. Diabetes Feb 2001, 50 (2) 217-226; DOI: 10.2337/diabetes.50.2.217
Merriam-Webster: Immunotherapy
Pharmaceutical Journal: Immunotherapy for type 1 diabetes: what’s in the pipeline?
