As our society’s waistlines keep expanding, researchers and entrepreneurs alike continue searching for novel ways to reverse obesity and its associated complications. Over the last few months we’ve covered everything from an inflatable gastric balloon to a device that sucks food directly out of the stomach. One of the devices we’ve been following, the EndoBarrier, has made some recent headway with the announcement of its ENDO trial. We spoke with GI Dynamics founder and chief technology officer, Andy Levine, to learn more about their flagship product.
Shiv Gaglani, Medgadget: Can you describe the history of GI Dynamics and the EndoBarrier?
Andy Levine: The origins of GI Dynamics date back to 2003. Spurred by the emergence of gastric bypass surgery and growing recognition of its therapeutic impact, I identified an opportunity to develop a technology that mimics the mechanism and effects of bypass surgery, but through a less invasive, reversible procedure. These ideas inspired the development of EndoBarrier and led to the founding of GI Dynamics.
Medgadget: What is EndoBarrier Therapy? How does it work?
Levine: EndoBarrier Therapy is a revolutionary approach to treating type 2 diabetes and/or obesity that doesn’t rely on medication or involve surgery to achieve its results. Delivered and removed endoscopically (i.e., through the mouth), the EndoBarrier device is a flexible, tube-shaped liner that creates a barrier between ingested food and the duodenum/proximal jejunum sections of the intestine. Essentially, EndoBarrier mimics the effects of a gastric bypass, but without the risks associated with surgery. There are no incisions, scars or lasting changes to the anatomy.
The EndoBarrier device is not designed to remain in the body permanently. It has been tested and approved for a treatment period of up to 12-months and can be safely removed at any time using GI Dynamics’ custom retrieval system in a short endoscopic procedure.
Medgadget: What are some of the most promising results you’ve received through initial testing of the EndoBarrier? What are some of the most problematic results?
Levine: Clinical trial and commercial experience to date involving more than 800 patients has demonstrated significant diabetes improvement and weight loss with EndoBarrier Therapy. Patients want a temporary, reversible procedure that enables them to achieve their blood sugar and weight loss goals in 9-12 months while avoiding the significant risks, complications, and side effects of a permanent surgical procedure. Our current data demonstrate that EndoBarrier patients are able to reach healthy blood sugar levels and lose an average 20% of their total body weight within one year. In addition, many patients are also able to reduce or eliminate their oral anti-diabetes medications. Initial studies have also demonstrated that EndoBarrier Therapy has sustained benefits on glycemic control and weight loss up to six months post-removal.
Last October at the Annual Meeting of the European Association for the Study of Diabetes (EASD), we reported new data demonstrating the promise of EndoBarrier Therapy in patients with type 2 diabetes and a lower body mass index (BMI) than the current target population of obese diabetics, providing an opportunity to expand the market for the product to overweight people living with type 2 diabetes.
We have amassed a strong body of clinical data and real-world experience for EndoBarrier showcasing the benefits on blood sugar control and weight loss, as well as improvements in other cardiovascular risk factors. We are continuing to build additional clinical data for EndoBarrier Therapy to help label expansion, as well as drive local reimbursement in key markets outside the U.S.
Medgadget: How long do you expect the ENDO trial to take? While this is being conducted what will GI Dynamics be focusing on?
Levine: In January 2013, GI Dynamics initiated a pivotal clinical trial of EndoBarrier in the United States. Called the ENDO Trial, it will enroll approximately 500 people living with uncontrolled type 2 diabetes and obesity at up to 25 sites in the United States. The trial is designed to assess improvements in diabetes over a treatment period of up to 12 months. The primary endpoint of the trial is improvement in HbA1c, a key blood sugar measure for diabetes. Secondary measures include weight loss and improvements in cardiovascular risk factors, such as blood pressure and cholesterol. To be eligible to enroll in the trial, people must have type 2 diabetes with an HbA1c of between eight and 10, and a BMI of 30 to 50.
The trial is slated for primary completion in June 2015, and based on supplemental information provided, the company hopes to submit a PMA at the end of 2015, gain approval at the end of 2016, and launch in 2017.
As we continue to advance our U.S. pivotal study, we are also focused on expanding global commercialization efforts for EndoBarrier. EndoBarrier is already approved and commercially available in Australia, Chile, Israel and several countries in Europe, including the UK, Germany, Austria and the Netherlands.
Medgadget: Do you have any insight into how bypassing absorption in the small intestine will affect the various hormonal levels, both locally and systemically? For example, since lipids will not be sensed until later on will that affect the release of bile due to cholecystokinin release?
Levine: We now have a lot of insight into the mechanisms of action of the EndoBarrier. In a Dutch study presented at EASD in 2011, blood hormone levels were measured in 17 patients. We found that certain key hormones involved in glycemic control and appetite regulation, GLP-1 and PYY, were impacted with EndoBarrier in positive ways. These hormone changes, along with likely more, allow for rapid improvement in type 2 diabetes. These data add to the growing body of evidence supporting the influence EndoBarrier Therapy may have on key intestinal hormones that control appetite and glucose metabolism, mimicking the effect of gastric bypass without surgery.
Although we have not yet measured bile output, it is likely not changed much as there are several hormone triggers for this that the EndoBarrier likely does not impact.
Medgadget: How about at the other end? What is the likelihood of steatorrhea and related conditions, and how may those be circumvented or mitigated?
Levine: The EndoBarrier does not cause fat malabsorption, which is a common misconception about the product. Rat studies have shown this and patients do not get fatty stool. As the device only bypasses a small part of the intestine, the body can still digest most of what is consumed in the distal bowel. Research shows that EndoBarrier works by modifying key gastrointestinal hormones involved in insulin sensitivity, satiety and weight loss.
Medgadget: Can you describe how you became involved in this field?
Levine: I had co-founded a medical device incubator in 2000 called Seedling Enterprises with John Cvinar and Josh Tolkoff. We were looking to start new companies and were exposed to the emerging field of gastric bypass surgery. John and I began to talk to physicians and read the literature, and realized there was an opportunity to exploit the unique attributes of gastric bypass, but with a minimally invasive intestine bypass…and away we went.
For more information, check out this animated video depicting the EndoBarrier: