Could a cancer drug preserve some beta cell function in those newly diagnosed with Type 1?

Preliminary results from 1 year findings of a 2 year randomized phase 2 clinical trial conducted on 67 participants were presented at the 2017 American Diabetes Association (ADA) Scientific Sessions in June by Stephen Gitelman, MD, of the University of California, San Francisco.  He explained that adults (ages 18-45 with an average age of 27) who were newly diagnosed with Type 1 diabetes were treated for six months with imatinib.  They displayed an improvement in beta cell function as well as a diminished need for exogenous insulin (the man-made kind that you inject) out to the 1 year mark of the study.  On the whole, participants tolerated the drug well.  These preliminary results certainly hold promise, but more research and larger studies are needed.  The goal of this phase two trial was to assess the safety and efficacy of imatinib as a novel therapy to be used in the treatment of Type 1 diabetes.  While the researchers had wanted to use children in the study, the FDA mandated that they would first have to demonstrate in a prospective trial conducted on adults that this drug offers a benefit.

In non-obese mice with diabetes, imatinib has already been shown to be able to both prevent diabetes and to reverse diabetes.  After treating the mice for 10 weeks and then withdrawing treatment, at least 50% of the mice stay in remission.

In this multi-site trial, participants were randomized 2:1 to get 400 mg daily of the study drug or placebo for six months.  Follow up another 18 months after the end of therapy is planned.  The initial A1c of the study participants was about 7.2%, and use of exogenous insulin was modest.  The primary outcome for the study was the area under the curve (AUC) for C-peptide over the first two hours of a four hour mixed meal glucose tolerance test, so that endogenous (the kind of insulin that a pancreas makes) insulin production could be evaluated.  At monthly follow up visits this was evaluated, and also at the 1 year visit.  Not surprisingly, endogenous insulin production fell steadily over the year in the placebo group.  However, the curve looked quite different in the treatment group, especially after the three month point–and at the one year mark, there was a significant difference between the two groups.  Participants from the treatment arm of the study used less exogenous insulin, especially in the first six months while they were receiving treatment.  At 12 months, there remained a difference between the groups.  This hints that the treatment might have improved beta cell function, letting them produce more endogenous insulin.  It’s also possible that it may have improved insulin sensitivity.  During the study, both groups had well-controlled A1c levels.

Of course, there have been some bumps in the road along with the success.  Participants in the treatment arm experienced more mild to moderate therapy-related adverse effects, namely shifts in cell counts and changes in liver function.  Researchers adjusted drug dose and these issues cleared up without incident.  It should also be noted that gastrointestinal side effects of nausea and occasional diarrhea and vomiting occurred.  These effects are known to happen with imatinib, and generally they resolve on their own.  Another consideration is that imatinib is a very expensive drug, with the generic version costing $3000-$8800 per year in Canada and roughly $45,000 per year in the United States.

The plan is for this study to go out to two years, and investigators will be evaluating the effect of age as well as dose on therapy response.  They will be determining whether the beneficial effects continue or diminish over the remaining 12 months of the study.  The researchers plan to eventually investigate the use of this treatment on children because after kids are diagnosed, they tend to lose beta cells faster.  Dr. Gitelman noted that there are various therapies that don’t seem effective in adults, yet their impact on children is significant.

Past clinical trials have often investigated target T cells.  It is possible that by combining imatinib with a T-cell therapy, a synergistic effect may be seen.

We are thrilled to see so much research being done to prevent and treat Type 1 diabetes, and hope that eventually Type 1 really does become Type None.