Many in the diabetes world have been closely following the work coming out of Douglas Melton’s lab at the Harvard Stem Cell Institute (HSCI), which has figured out a way to produce human insulin-producing beta cells on a large scale. The next task is figuring out how to get the cells through the FDA approval process and to market. In late September, I went to a panel at Harvard about the infrastructure Melton and his colleagues have created to push that process along. There, it became clear that like Boston University biomedical engineer Ed Damiano, who is seeking FDA approval for the bionic pancreas, Melton has decided to break the type 1 diabetes problem into two parts, planning to seek FDA approval for the stem-cell derived beta cells, and later to seek approval for the encapsulation technology necessary to protect them from the autoimmune attack that characterizes type 1. (The bionic pancreas is designed to be a dual-hormone pump—insulin to bring blood sugar down, and glucagon to keep blood sugar from going too low; but Damiano and his company Beta Bionics are seeking FDA approval for an insulin-only pump first, and later will seek approval for a dual-hormone pump.)
The HSCI has now joined with others from the medical field to form the Boston Autologous Islet Replacement Program (BAIRT). The moderator of the panel called it “the full spectrum of the Boston biotech ecosystem.” Aside from HSCI, the program includes Semma Therapeutics, a biotech company named after Melton’s children, Sam and Emma, who both have type 1; Joslin Diabetes Center, Brigham and Women’s Hospital, which will be involved in recruiting patients and transplanting beta cells; and the Dana-Farber Cancer Institute, which already has in place a cell production facility.
Melton started off the panel by saying that the basic goal of his work is to replace insulin injections with stem cell injections—“providing nature’s own solution” to the problem of diabetes. The difference between a healthy beta cell’s ability to measure sugar and the best constant glucose sensing technology is vast: “Beta cells read sugar a thousand times a second, a glucometer reads it every 5 minutes. They have a long way to go to catch up with millions of years of evolution.”
While Melton and his colleagues seem to have solved the problem of how to turn induced pluripotent stem cells into beta cells in the lab, he admits that he needs help translating the work to people. “As my children would say, ‘We don’t care about making more rats non diabetic.’ But I’m a basic research scientist; I couldn’t do this on my own.”
That’s where the rest of the BAIRT team comes in.
Melton’s lab licensed its beta cell technology to Semma Therapeutics, which is working to bring the technology from the lab to the clinic. Semma’s CEO and co-founder, Robert Millman, was cautious about the project’s timeline: “There are a lot of scientific steps that have to be gone through and a lot of regulatory steps. The FDA is working with us very early in the process—that’s encouraging. I would love to say we’ll be able to treat Doug’s kids; however, how long it will take us to get through the process is unclear.”
The initial study, which will start enrolling next year, will involve about ten patients, who will have the stem-cell derived beta cells injected into their forearms, in the hopes that the cells will start producing insulin within the body. These patients will be people who have become diabetic because their pancreases were removed due to pancreatitis—not type 1s whose ability to create beta cells has been curtailed by autoimmune attack. In other words, this study is only about the efficacy of the cells themselves. In order for the cells to get approved, they will have to pass a number of hurdles. As Millman explained: “We have to show the FDA that we have a product that won’t do something bad to the body. We have to show that these cells are committed to being beta cells; and we have to show that they are regulated and functioning properly, that they don’t secrete too much insulin.”
In terms of protecting the cells from autoimmune attack, BAIRT is working on a couple of different initiatives, both short term and long term. A short term solution would be to protect the cells by a physical barrier, which would nevertheless allow the cells to release insulin into the body in response to glucose signals. Melton described this physical barrier as “like a tea bag.” The sugar is like the water coming into the bag; the insulin released from the beta cells is like the tea that floats out. But the long-term goal, he said, “is to understand why the immune system is making this mistake, and then kill off this immune response.” Having an unlimited supply of beta cells will help in this process. “Once we have a patient’s own beta cells you’ll be able to interrogate the immune system in a way you haven’t been able to,” Melton said. His lab is also looking to the field of cancer immunotherapy, and ways to adjust the immune system so that it would no longer attack beta cells.
When asked about how much it would cost to bring beta cells to market as a treatment, Millman first said “lots,” and then added that he thought the whole program would cost about $30 million. But, as Melton pointed out: “This year 22 billion dollars of insulin will be injected into people. We are talking about millions of dollars to replace that.”
Given the large amount of money that pharmaceutical companies make from selling insulin, audience members pointed out that Big Pharma is unlikely to support this technology—the goal of which is to let people with type 1 diabetes live free of insulin injections. Melton pointed to another potential source of support: insurance companies. “This is a lifelong disease that costs thousands of dollars a year to treat. So it seems to me that insurance companies should also be interested in this. Treatment is expensive over a lifetime.”
I talked with Melton a bit after the event, and he made it clear that his goal is to come up with a treatment that changes the face of diabetes—essentially a cure, drawing upon the human body’s own perfectly calibrated system—and in so doing that pulls the whole multi-billion dollar diabetes market along with it. “It’s like Tesla—GM and Chrysler weren’t going to develop the electric car until Tesla came along and proved it could be done, and that people wanted to buy the cars. Now all those companies are jumping in to be part of that market, for economic reasons.” But of course Melton, with his two children with type 1, is not doing this for economic reasons. “This treatment could improve people’s lives. You can’t put a number on that.”