Maybe it won’t cure diabetes. But a compound slated to begin a new Phase 2b clinical trial early next year stands a good chance of knocking diabetes back into remission.
Almost never do I write about new drugs unless they are at least in in the final stage of development, a Phase 3 trial. The odds are against them.
Of 100 drugs for which developers submit investigational new drug applications to the Food and Drug Administration for approval, about 70 will successfully complete Phase 1 trials and go on to Phase 2. About 33 of the original 100 will complete Phase 2 and go to Phase 3. And 25 to 30 of the original 100 will clear Phase 3.
And of the thousands of articles that I have written about diabetes in the past 14 years I can remember only three spotlighting drugs that hadn’t entered Phase 3. One was my column on the American Diabetes Association’s website in 2002 about the compound that came on the market three years later as Byetta.
But so many people keep asking me about about INGAP that I knew I had to check out its current status. And during the past two and one-half years INGAP has not only stayed the course but is beginning to move to market.
INGAP stands for islet neogenesis associated protein. That’s not only a mouthful of a name, but also nowadays the term “regeneration of islet cells” is replacing the too technical “neogenesis.” Maybe we should start calling it RICAP — but that might confuse people even more.
By whatever name we call it, this natural protein stimulates regeneration of islet cells capable of producing insulin and other metabolic hormones. It stimulates the development not just of beta cells but also of fully functioning islet cells with all of the metabolic hormones that can be regenerated from precursor cells residing in the pancreas. We can think of it as turning back the clock on the diabetes.
The many calls and emails that I keep receiving prompted me to contact some of the top people at the start-up company that is developing INGAP. This week I interviewed Zoe Heinenman Myers, vice president of marketing for Kinexum Metabolics Inc. in Burnsville, Minnesota, and then at length with Lisa Jansa, the company’s new CEO.
She is one of the company’s co-founders, along with Alexander Fleming, MD, a former supervisory medical officer in the division of metabolic and endocrine drug products at the Food and Drug Administration, and Kevin Roche, a former CEO of Ingenix. Dr. Fleming and Lawrence Rosenberg MD, who together with Aaron Vinik, who now leads Eastern Virginia Medical School’s Strelitz Diabetes Center, discovered INGAP, reviewed its status last year in “Prospects and Challenges for Islet Regeneration as a Treatment for Diabetes: A Review of Islet Neogenesis Associated Protein.”
What other drug candidates might lead to regeneration of islet cells? Lisa says that she knows of only one such company that has a compound in a Phase 2 trial, Transition Therapeutics in Toronto, Canada. They call it TT223, and they are currently recruiting people with type 2 who are taking metformin and/or a thiazolidinedione.
“We are cautiously optimistic that INGAP therapy will be the first major breakthrough since the discovery of insulin,” Lisa told me yesterday. “It turns back the clock on diabetes.”
Lisa is careful not to claim that INGAP will cure diabetes. In fact, the next clinical trial won’t be one testing INGAP alone. “We are seeking to be the first in a combination trial of INGAP and an immune modulator,” she said.
Immune modulation is an emerging field in the medical treatment of viral infections. Immune modulators work by introducing an agent into the body that boosts specific areas of the immune system. While they can arrest the loss of insulin secretion in type 1s, alone “they have not caused permanent disease remission or restored insulin secretion.”
Kinexum is now in “active discussions” with several other companies to pick the immune modulator that the trial will use. I know of just four possibility candidates. They are Diamyd Medical’s GAD65, Andromeda Biotech’s DiaPep277, Tolerx’s Otelixizumab, and DiaKine Therapeutics’s Lisofylline. Here is a link to a poster in PowerPoint (or Keynote for the Mac) format about the potential combination of Lisofylline and INGAP.
Lisa is optimistic but cautious about whether this combination will cure diabetes. “By toning down the autoimmune response — modulating it — in advance and then regenerating islet cells we think that this combination has great promise. We do think that INGAP in combination with one of the immune modulators will be curative,” she says. But she also says that talking about a potential cure is “a touchy subject.” She would rather “err on the side of being ultraconservative, since we are sensitized to so much disappointment by people with diabetes.”
The upcoming Phase 2 trial will be of adult type 1 patients who were diagnosed at least two years ago. The principal site of this trial will be at McGill University in Montreal, Quebec, Canada. Endocrinologist George Tsoukas, MD, is the principal investigator. “He is right now screening patients,” Lisa says.
So only people who live near Montreal are eligible? I asked Lisa. “No,” she replied. “They can live anywhere. They will get 30 days of the study material and have visits at baseline, and then at 30, 60, and 90 days and take it by subcutaneous injection.
Why is the next trial limited to type 1s? “Ultimately, it will be a therapy for any insulin-dependent person,” Lisa says. “But we are strategically targeting type 1s as our primary pathway to approval.” With this strategy she’s hoping for quicker approval, but wants to follow this type 1 study with a study of people with type 2 diabetes in 2009 or 2010.
The hardest questions that I asked Lisa was to look ahead and guess when a Phase 3 trial would begin and when she thought that INGAP might be available for us to use. She replied that she hopes the Phase 3 trial could begin within two to two and one-years and it could be available to people with type 1 diabetes within three years.
If and when we are able to use INGAP, it won’t be a single shot. It’s like that at least when it first comes to market it will be daily injections for up to three months. However, they don’t know yet if we would have to take booster shots after that.
Something as big as INGAP won’t come cheap. “We don’t anticipate that it will exceed $20,000 for a single course of treatment,” Lisa told me. Later, however, she is confident that as they scale up production they will be able to bring the cost down.
We can expect to hear a lot more about INGAP in the coming months, and this is just the first of many articles that you can expect to read about it. They are just now ready to come out from behind the curtain, Lisa says. “Exciting changes are coming.”
This is a mirror of one of my articles that was originally published on Health Central.