There must be a million ideas to help the many millions of obese Americans lose weight. Today, doctors will get a glimpse at a first-of-its-kind treatment from Boston-based Gelesis, where scientists have created a capsule that expands in the stomach to make people feel full and eat less.
Gelesis has said little about this idea since the company was founded with seed financing from Puretech Ventures, plus another $16 million from OrbiMed Advisors, Queensland BioCapital Funds, Puretech, and others in January 2008. Now Gelesis has results from a clinical trial of 95 people who were randomly assigned to take the company’s superabsorbent hydrogel capsules (Attiva) or a placebo. The capsules helped people feel full after meals and less hungry in between, researchers said. And, importantly, the treatment was well-tolerated. The findings were presented at the American Association of Clinical Endocrinologists annual meeting in Boston.
Anyone following the news knows that the obesity epidemic in the U.S. has gotten so big that it poses a threat to the healthcare system, and, simultaneously, represents a monster business opportunity. Health officials now say two-thirds of U.S. adults have become overweight or obese, which raises the risk for a whole raft of other conditions like diabetes, heart attacks, and depression to name a few. Doctors often advise people to eat healthier and exercise more, without much luck. A few biotech companies are racing to win FDA approval of new drugs, but Big Pharma companies have tread cautiously in this field since the fen-phen debacle of the ’90s. Gastric bypass surgery to shrink the stomach can help people, although the procedure carries significant risks.
The idea at Gelesis is to come at this problem with a completely new method. It’s essentially a way to reduce stomach volume without subjecting people to the invasiveness and potential complications of surgery.
“For the first time a group was able to overcome the enormous technical hurdles in creating a super-absorbent polymer,” said Robert Langer, the prominent bioengineering professor at MIT, in a company statement. Langer isn’t a founder of the company, although he advised Puretech Ventures on the technology before the firm seeded Gelesis in 2006. Based on today’s results, Langer added: “This opens the door for entirely new uses of polymers in medicine.”
I took a closer look at this yesterday during a conference call with three key players of Gelesis. Daphne Zohar and Eric Elenko of Puretech Ventures, and the co-inventor of the technology, Alessandro Sannino, a professor of engineering at the University of Sallento in Italy, who has been working on this idea for 15 years. The company also has recruited a lot of prominent advisers with different layers of expertise. James Hill, a University of Colorado professor and past president of The Obesity Society brings obesity knowledge; Allan Geliebter, a phychologist at St. Luke’s-Roosevelt Hospital is a pioneer of the gastric balloon; Lee Kaplan of Massachusetts General Hospital Weight Center is a leading researcher in gastric bypass surgery. John LaMattina, a former president of Pfizer’s global R&D operation, has joined the Gelesis board.
You can take a look at how this technique is supposed to work by watching this animation on the Gelesis site, which lasts a little less than four minutes. But’s here the concept in a nutshell: Gelesis has developed a superabsorbent polymer from some unspecified food source. This material, about the size of a grain of sugar, is designed to swell up more than 100-fold in volume when it comes into contact with water. So this “hydrogel” can be packed tight into a capsule that’s small enough for people to swallow. When you drink a water to down the capsule, it releases all those superabsorbent and expanding hydrogel particles in the stomach to at least partly fill you up so you have less room for food.
Once the hydrogel particles are released and filling up with liquid, they put pressure on the walls of the stomach, sending a signal to the brain that says the person is full, and it’s time to stop eating. The particles mix with the food, which keeps the food in the stomach longer. Eventually, stomach acids then shrink the particles during digestion, so they release the water, and they can travel with the food to the small intestine. The particle can re-swell to an extent at that part of the journey, and increase the viscosity in the small intestine so that sugars and fatty acids get absorbed more slowly there. The hydrogels then proceed to the large intestine, release their water, and disintegrate. The Gelesis product is designed so it never gets absorbed into the bloodstream like a drug. It gets excreted in the feces.
The technical challenges to navigate this biological journey sound immense. One big trick was to find a combination of food-grade natural polymers that could cross-link together in a 3-D form to expand properly, Sannino says. Then there was the need to make it absorbent enough. The next big challenge was making the particles sensitive to ever-changing pH conditions they encounter from the stomach through the intestines. And the latest task has been to set up an efficient production system.
Gelesis isn’t saying where the material comes from for the hydrogel particle, or how much the raw material costs. But it does provide “nice commercial margins,” based on the models Gelesis is using for what such a drug might cost in the marketplace, Elenko says.
Interestingly, even though this product is taken in a capsule, Gelesis believes it could technically be considered a medical device, not a drug, by the FDA. That’s an important distinction to make, since the material works mechanically to treat obesity, rather than being absorbed into the blood like a drug. If the capsules are considered a device, that would change the regulatory pathway Gelesis would need to clear before reaching the U.S. market.
So what did the clinical trial show in detail? The study enrolled 95 people at Gemelli Hospital in Rome, Italy. The average person had a body-mass index of 31, the equivalent of someone who’s 5-foot-6 and weighs 190 pounds. They took a placebo, or 2 grams of the Gelesis product in five oral tablets, with a glass of water before breakfast, lunch, and dinner. They were asked to fill out a questionnaire immediately after their meal, 30 minutes later, and an hour afterward.
The people reported that they felt an increasing sense of fullness (known formally as satiety) after each meal, and that when it was taken before lunch, people felt significantly less hungry at dinnertime. The feeling of hunger didn’t completely go away between breakfast and lunchtime, researchers posited, because people didn’t eat as much at breakfast to fill up their stomach and get the full benefit of the hydrogel.
The treatment was safe and well-tolerated, researchers said. About 16 percent of the people studied reported at least one symptom across the treatment and placebo group. About 7 percent reported nausea, about 4 percent complained of constipation or stomach ache, while just one person reported diarrhea. The incidence of side effects was similar to what overweight people often experience in placebo groups of similar trials.
Of course, this was just the first clinical trial for Gelesis, so it wasn’t really designed to measure the treatment’s effectiveness. Any treatment for weight loss is going to have to show it can help people lose weight over a yearlong period, according to the FDA’s current guidelines for obesity drugmakers. And that treatment aspires to help people who are moderately overweight—not the morbidly obese. Since overweight people have a less severe condition, the FDA is going to want to ensure any new therapy has a very clean safety profile. And there is at least one well-financed competitor, Lexington, MA-based GI Dynamics, which is also pursuing the promise of a device that’s a less-invasive alternative to gastric bypass surgery.
The Gelesis team knows all that, and is thinking hard about the next steps. The company has some government grants and partners providing non-dilutive sources of capital, and it is in strong enough financial shape that it doesn’t need to raise another venture round anytime soon, Zohar says. The company is considering the next steps in clinical development.
But these sound like heady times at Gelesis. The co-inventor, Sannino, said he has tried the product out himself, outside of the rigorous setting of a clinical trial. A few of the Gelesis investors have too, just, I suppose, as part of doing thorough due diligence. “It is quite surprising how you feel,” Sannino says. “It was like having eaten a plate full of spaghetti.”
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