I’m live-blogging from the 2012 ADA Scientific Sessions in Philadelphia. Here’s coverage from Day 1 and Day 2, including an update on Tandem Diabetes Care’s new t:slim insulin pump, the progress with anti-CD3 antibody/teplizumab trials, the ongoing controversy over LADA, the differences between CGM monitoring systems, an interview with Medtronic’s VP of research and development in its diabetes unit, and the importance of exercise and diabetes management. It’s been a whirlwind! I’m also tweeting from catherine_price . Send questions and comments my way.
12:24 Conversation with Mads Krogsgaard Thomsen, Executive VP and Chief Science Officer at Novo Nordisk About Oral Insulin
Yes, you heard me right: oral insulin. As in insulin you take as a pill, not as a shot. My reaction: Whaat?
Because as everyone with Type 1 knows, today’s insulins don’t work as pills. They can’t: insulin is a protein, and if it gets to the stomach, it’s digested like food. If it somehow gets past the stomach (unlikely), it then faces another challenge: it’s a large molecule compared to what our gut is normally willing to absorb and, therefore, it doesn’t actually get into circulation. In the words of Mads, “Normally the gut will only take very small molecules and here comes a huge protein. How on earth will that get across?” These are daunting challenges — in fact, Mads said that only 0.05% of insulin taken orally will ever make it out alive.
The solution, as Novo sees it, is to somehow protect the insulin molecule while it’s in the harsh environment of the stomach (likely with what’s called an enteric coating, the same type of tough exterior that fish oil manufacturers use to try to avoid giving you fishy burp back), and then to develop a way for it to be transported into the gut. Then, once it makes it to the gut, you need to engineer a way to increase absorption.
They started by putting insulin into simulated (or real) gastric juice, and mapping where the weaknesses were — i.e. how and where the insulin was being degraded during the digestive process. “When we found weak spots, we chemically and genetically engineered more stable structures into them,” said Mads. That process alone gave them a ten-fold improvement. Granted, that means that 0.5% of the insulin was making it out as opposed to 0.05% — still not a lot — but as Mads put it, “You’re coming from nowhere. Okey dokey.”
Then they modified the molecule in a way that made it more likely for it to get across the gut barrier, resulting — in animal trials — in another ten-fold increase in availability: a total of 5 percent. “It doesn’t sound like much,” said Mads, “but it can be enough.”
The reason it can be enough is, in part, because of the ultimate goal of this oral insulin (I’m sticking to oral insulin for this post but want to emphasize that they’re really working on, and in fact are further along with, GLP-1 agonists): they’re hoping it can be a replacement — or booster — for basal insulin. Their primary target market is people with Type 2, partially because the oral insulin is likely to work better in people whose pancreases can still cover a bit of the ups and downs. And they’re also hoping that an easy-to-take oral insulin pill might be helpful to all the people who are pre-diabetic (with elevated HbA1cs) — in other words, they’re going for the widest audience possible
The reason 5 percent could be enough, then, is that your goal is really consistency, rather than quantity: you want to have a slow and steady baseline rate of insulin that is not affected by say, a day when you get food poisoning or, conversely, forget to eat your Wheaties (who would think colon health would ever affect insulin availability?). And that’s the other good thing: Novo’s new insulins have really long half-lives, which means that they stick around in the body for a long time before breaking down. So ideally you’d take this pill regularly to give yourself baseline insulin, and then supplement it with whatever other insulin you might need.
Speaking of which, it’s important to note that they are not working on oral bolus insulin, just basal. The reason is simple: when you take oral insulin pills with food, a food/drug interaction occurs and the pills don’t really work. Since boluses are nearly always associated with food, it’s a no-go.
If you’re Type 1 and frustrated that you’re probably not going to be able to replace shots with pills, here’s something to make you feel better: Novo is also working not just with embryonic stem cells (with the goal of perhaps being able to provide booster shots of beta cells you’d get once or twice a year), but with using oral insulin as a prevention for Type 1 (or to help those who are newly diagnosed). The idea is to introduce insulin to your body in a non-threatening way, to try to encourage your immune system to accept it as a friend rather than a foe that needs to be hunted down and destroyed. In order to do so, they’re working on an oral insulin that looks like insulin to the body, feels like insulin, but doesn’t actually lower blood sugar — so you can train your body to tolerate it without running the risk of hypos.
(Side note: I also asked him about previous prevention trials using oral insulin — namely, the Diabetes Prevention Trial that was not successful using oral insulin to prevent Type 1. He said that the amount of insulin given to participants was decided pretty randomly, and that the insulin they used was not the protected type that he is working on, meaning that only a tiny percentage likely ever made it into circulation. Future trials using effective oral insulin formulations might have very different results — and this is something Novo is actively working on. They’re also working on making Novolog even faster, which would obviously be fantastic.)
As for timeline, Novo is currently in phase 1 clinical trials with oral insulin — which means it’s a long way from actually being available, but which is still extremely exciting. They’ve got literally hundreds of people working on the project, and Mads estimated that a half of Novo’s research budget is being used on oral therapies.
I was really thrilled to have the chance to talk with Mads, and am now equally thrilled to have a chance to publicly express my appreciation for the work he and Novo are doing. I personally am fine with companies profiting off of products that help me live my life better, but Novo also seems truly committed to improving the lives of all people with diabetes, even if the market is small.
For example, a project like using oral insulin as a prevention for Type 1 would only impact a small number of people because, as he put it, “You often don’t pick up patients early enough.”
“But if it can be done, it should be done,” he continued. “And we should do it.”