In part 2 of this exclusive interview, Dr. Faustman discusses the challenges of dosing BCG correctly, and the difficulties of defeating autoimmunity in humans.
Steve Freed: Has this been tried before and failed?
Dr. Faustman: That’s kind of interesting. So there was an early trial, 25 years ago in Israel, where they tried one dose of BCG at the onset of type 1 diabetes. They thought it worked, so that spawned three more trials to try to use one dose. Nobody knew the mechanism. In three subsequent trials in France, the U.S., and Canada, they said ‘we don’t see anything.’ Those trials remind me of doing an early insulin trial, where you gave one dose of insulin and you looked a year later and you said insulin doesn’t work, everybody died that had type 1 diabetes. Unless you know the mechanism and know how many doses and how much dosing, there is little hope. These trials globally are now all mechanistically based, looking for how we can dose the BCG correctly in order to get a permanent change in immune response. So we’ve learned a lot in those last 25 years and maybe those early Israeli studies were really correct but people didn’t know that you needed more than one dose of insulin or you needed more than one dose of BCG.
Steve Freed: So you’re going to be starting phase 2?
Dr. Faustman: We’re actively in phase 2 right now. Phase 2 is a double blind placebo controlled trial using multi-dosing BCG in people with long term type 1 diabetes with no complications and a little bit of remaining C-peptide from the pancreas.
Steve Freed: What about for people in preventing diabetes?
Dr. Faustman: Well, that’s good. We only have so much money, so if somebody wants to come in and donate for us to do prevention trials, we’re ready to go. There is some prevention trial data that got published two years ago out of Turkey. That data showed one vaccine doesn’t work in childhood from birth to age of 12. Two vaccines don’t work but greater than two vaccines throughout childhood totally prevents the onset of type 1 diabetes. So prevention trials should probably start. But as you know those have to go 12 years. So it’s money-permitting that those trials will be moving forward.
Steve Freed: How many different arms do you have in this trial?
Dr. Faustman: So, we have two arms. It’s a 2 to 1 randomization, it’s 150 cohorts. Our phase 1 trial used two doses four weeks apart. That long-term follow-up data will be published later on this year. This trial — because we know from the multiple sclerosis trials, it takes a while for the permanent immune effects — we’re going to be dosing more, so we’re going to be giving two doses like we did in phase 1 and a yearly booster for four more consecutive years.
Steve Freed: Are you going to be presenting anything about this at the ADA?
Dr. Faustman: Yes. We have a presentation at the ADA about the global BCG trials and where there’s increased efficacy in how people are designing those trials and what are the tough endpoints people are striving for? As you know, these are unique immune intervention trials. The first immune intervention trials working with people that have long standing Type 1 diabetes, not just new onsets.
Steve Freed: So, you have a lot of experience in different trials and working with diabetes. What are some other possibilities like regeneration of beta cells? We’ve seen a lot of information about that. I’m sure you’re familiar with IGAP and where that’s going. Where do you think that might take us?
Dr. Faustman: I think that everybody has to pursue their dream until we get to the golden gates and diabetes is cured. So we don’t yet know. We meaning the global community, not just Denise Faustman here at Boston. We don’t yet know the full regenerative capacity of the pancreas of a human. If you’re an end-stage autoimmune diabetic mouse, we’ve got you covered. Those pancreases of mice, when we use BCG, fully regenerate. It’s just beautiful. Huge islets. So there’s no doubt. Everybody scientifically has proven it over and over again. When you give BCG to an end-stage naturally diabetic mouse, the regenerative process takes over and insulin is full reconstituted permanently for these animals. We’re going to have to see as we go through these trials where now we’re aiming to take away the autoimmune process, how much of the human pancreas after 20 years can regenerate? That’s where, as alluded to by other groups, if we can really for the first time take away the autoimmune process, then allow combination therapy for those people who might have less regenerative capabilities than maybe people who are younger or have less burden of T-cells.
Read the rest of the interview: