BB&T Contributing Editor
NEW YORK — Cannacord Adams' (Vancouver, British Columbia) third annual Diabetes and Obesity conference, held here in May, featured emerging companies developing products for blood glucose monitoring, insulin delivery and devices use in bariatric surgery.
Obesity and diabetes are linked clinical issues that cause poor health and early death. In the U.S. one in three people struggle with obesity and over half are overweight. More than 10% of adults in the U.S. are diabetics, although many are undiagnosed. The number of diabetics is estimated to grow from 18 million people worldwide in 2000 to 50 million by 2020.
Worldwide sales of blood glucose monitors is projected to reach $10 billion in the next few years and is dominated by four major marketers: Roche Diagnostics (Indianapolis), a unit of Hoffmann-La Roche (Basel, Switzerland); LifeScan (Milpitas, California), a subsidiary of Johnson & Johnson (New Brunswick, New Jersey); Bayer Healthcare (Tarrytown, New York), a unit of Bayer Corp. (Leverkusen, Germany); and Abbott Laboratories (Abbott Park, Illinois).
Glucose measurements for ICU patients
More than half of ICU patients suffer from stress hyperglycemia and are placed on insulin. For these patients, laboratory accuracy is needed in detecting blood glucose levels and available glucose meters are inadequate.
OptiScan Biomedical (Hayward, California) is developing OptiScan, a continuous glucose monitoring system for use in managing in-hospital hyperglycemia, especially for ICU patients. It uses multiple wavelengths in the mid-infrared spectrum for automatically measuring at 15 minute intervals the glucose level in plasma. It was claimed to yield more accurate test results than from blood specimens.
OptiScan also controls insulin delivery in order to prevent hypoglycemia. Following several IDE-related meetings with the FDA, the company is conducting two clinical trials and expects to receive regulatory approvals and market launch in the U.S. and Europe in early 2010.
OptiScan Biomedical is in discussion with potential partners for selling into the ICU market. There are 14 U.S. patents covering its technology and the company is exploring other applications such as for diagnosing sepsis. ICU patients with stays of one week or longer were said to have a 50% incidence of sepsis.
Luminous Medical (Carlsbad, California) also is developing an automated continuous glucose monitor using a near infrared system that can read whole blood and is designed for use in the ICU. Currently, glucose measurements for ICU patients require manual sampling for obtaining circulatory blood readings.
Luminous' automated blood glucose monitor yields results in less than 10 minutes. It possesses an embedded automated insulin dosing algorithm and automated programming for insulin pumps. It has hospital information system connectivity which is now a requirement in hospitals.
The company expects to complete a pivotal clinical trial by the beginning of 2010 and file a 510(k) by mid-2010. The total market size was estimated to be almost $1 billion, comprising $300 million for the consoles and $625 million for disposables. The NICE-SUGAR study (see below) was cited as showing the need for automated glycemia control rather than manual testing.
The presence of hyperglycemia in critically ill patients has been linked to adverse effects including multiple organ failure and death. However, whether better control of blood glucose can result in more patients recovering from critical illness is currently unclear.
The NICE-SUGAR study is a multi-center, international, open label, randomized controlled trial of blood glucose management comparing the effects of two blood glucose targets on mortality in patients who are in the ICU for at least 48 hours. Over 35 ICUs in the U.S., Canada, Australia and New Zealand are participating in this pivotal 6,100-patient trial, for which 3,000 patients have already been enrolled.
Generally, tight control of blood glucose sugars in people with diabetes is beneficial in reducing the risk of blindness, kidney disease and other complications. However, the New England Journal of Medicine reported in its March 24 issue that trying to aggressively control blood sugar levels of critically ill patients may not be the best approach. Researchers reported a six-fold increased risk of hypoglycemia in those receiving intensive treatment, compared to a control group.
Continuous glucose monitoring
Sensors for Medicine (Germantown, Maryland) is developing a long-term glucose monitor that is implanted for 6-12 months under skin in an outpatient procedure. The micro-miniaturized sensor is the size of a grain of rice. It is designed to automatically measure interstitial glucose every few minutes.
The implant utilizes patented optical chemical sensing technology wherein a glucose-sensing fluorescent polymer yields a signal that generates an electronic pulse that varies with the glucose concentration.
The sensor implant communicates wirelessly with a small external reader, allowing the user to monitor glucose levels continuously or on demand. It can be remotely interrogated by a reader to track the rate of change in glucose levels and warn the user of impending hypo- or hyperglycemia. Data can be downloaded and is stored for up to four months.
The company is working toward achieving recalibration at only 3-month intervals, which contrasts with currently used glucose monitors that require daily recalibration. The company recently entered a human trial and initial results are as favorable as found in earlier tests on rabbits. A second phase of a pilot study will soon begin followed by a pivotal study next year with plans for submitting a PMA in 2011.
Other applications for its optical chemical sensing technology are being considered such as for biomarkers of cardiovascular disease. The company receives modest revenues from the sale of oxygen sensors.
Dexcom (San Diego) launched in March its Seven Plus, a stand alone continuous glucose monitor (CGM). It includes a disposable sensor that can be inserted by a patient and used continuously for up to seven days, a transmitter, and a small handheld receiver. It has increased accuracy over earlier CGM products, an added event marker, more discrete transmitter, and a new algorithm with enhanced software capabilities for providing greater analysis of readings.
The Seven Plus CGM has the smallest sensor on the market.
Competing CGM products are the FreeStyle Navigator from Abbott Laboratories and the Paradigm Guardian REAL-Time CGM system from Medtronic MiniMed (Northridge, California), a subsidiary of Medtronic (Minneapolis). All large insurance carriers now provide coverage for continuous glucose monitoring.
Dexcom is focused on the Type 1 diabetic market, but plans to explore opportunities for Type 2 diabetics in the future.
Dexcom has entered into non-exclusive development partnerships to integrate its CGM system into insulin delivery pumps sold by Insulet (Bedford, Massachusetts) and Animas (West Chester, Pennsylvania), a Johnson & Johnson company. Dexcon is collaborating with Edwards Lifesciences (Irvine, California) in the development of a CGM device for the hospital market which it expects to launch by mid-2010.
Insulin delivery devices
Calibra Medical (Redwood City, California) is developing Finesse, a disposable insulin delivery patch that is targeted at the users of manual syringes and insulin delivery pens, but not the insulin pump market. The device is designed in four models and is worn under clothing.
Bolus doses of insulin are released upon the push a button through the clothing, allowing for very discreet administration of insulin. The device holds 200 units of units which is sufficient for a three day supply. Every three days the patient fills the Finesse patch with insulin, adheres it to the body and deploys a flexible plastic cannula.
The device takes 3 seconds to administer. It is lightweight and can tolerate rough and wet conditions. Its assembly can be automated and most components are plastic. Calibra is currently submitting data to the FDA for 510(k) clearance and anticipates being on the market in 2010.
Insulet focuses on the Type 1 diabetes markets which comprises 1.2 million people in the U.S. of which 300,000 are currently using insulin delivery pumps. By the end of 2008, 10,000 diabetics were using Insulet's OmniPod insulin management system. It is a disposable insulin infusion device that features two easy-to-use parts with no tubing, a fully automated cannula insertion, and a handheld wireless personal diabetes manager (PDM). The device is replaced after three days.
A second-generation PDM will soon to be launched which offers data download capabilities and a color screen. The company's next generation OmniPod is expected to be available by the end of 2010.
Insulet has a new manufacturing facility in China in conjunction with its partner Flextronics (Singapore), which will have the capability for the annual production of 350,000 to 400,000 OmniPods.
Insulet is pursuing the use of its OmniPod to deliver other drugs. It has an agreement with Ferring Pharmaceuticals (Saint-Prex, Switzerland) for use of the OmniPod to deliver a fertility drug and will request CE-mark approval later this year. It also has signed a deal with a major drug company to study the potential for use of the OmniPod to deliver a multiple sclerosis drug.
It also has a program exploring use of the device for treating gestational diseases and has studies underway with another company for its use in treating Type II Diabetics.
Two companies that have developed insulin pumps and are monitored by Canaccord Adams but did not made presentations are Medingo Medical Solutions (Yokneam, Israel) and Nilimedix (Haifa, Israel).
Medingo's Solo insulin dispensing patch has two parts, a miniature dispensing patch and a remote control unit which allows the patient to program the system and deliver insulin remotely. The remote control includes an integrated blood glucose monitor. It is a discrete and flexible insulin pump and has no tubing.
Nilimedix's programmable insulin pump has been granted FDA clearance and the CE mark. It uses a wireless remote monitor and can be attached as an adhesive skin patch or on a belt clip. Its platform technology is based on a proprietary pressure triggered release mechanism, controlled by a unique valve and sensor system. The current design holds 300 units of insulin and a 200-unit model is under development.
Bariatric surgery, weight loss procedures
Gastric banding and gastric bypass are the most commonly performed surgical procedures on obese patients for weight loss and together amount to about 300,000 procedures in 2008. There are currently, 15 million to 16 million obese candidates for bariatric surgery in the U.S. Restrictive operations that make the stomach smaller, such as adjustable gastric banding (gastroplasty procedure), create a full feeling after a small meal.
Mitchell Roslin, MD, chief of bariatric surgery at Lenox Hill Hospital (New York), provided an update on endoscopic procedures for obesity. He has performed more than 6,000 bariatric procedures. The problem is maintaining the weight loss and not initially losing weight.
Roslin noted that "the first three month results mean nothing." The biggest part of his practice is placing lap bands on patients that had gastric bypass procedures. Bariatric surgery moved into the mainstream with the advent of laparoscopic surgery. Currently, there are 150,000 lap band procedures performed annually in the U.S., or 48% of all bariatric surgeries. Although the media highlights the problem of obesity, it is still a fight for obtaining approval for reimbursement.
Incisionless, minimally invasive procedures
GI Dynamics (Lexington, Massachusetts) uses a mechanical bypass procedure that is similar to bariatric surgery. EndoBarrier uses a Teflon-like material that is two feet long and is packed in a small capsule.
It is endoscopically placed using a dual lumen catheter in a 20-minute to30-minute procedure that is performed using direct visualization as well as fluoroscopy. It lines the intestines and serves as a physical barrier to prevent food from coming in contact with the wall of the intestine.
The device changes the metabolic pathway by controlling how food moves through the digestive system which is similar to the effect of gastric bypass surgery. The company has treated some 234 patients in eight clinical studies on obese and Type 2 diabetic patients in the U.S., South America and Europe.
Feasibility studies are being conducted to enable long-term and/or permanent implantation. A pilot study has been completed on a second-generation device which showed significantly greater weight loss.
GI Dynamics received the CE mark for the EndoBarrier in January and plans to launch the product in Europe in 2010 on obese diabetic patients.
Satiety (Palo Alto, California) has developed the TOGA procedure, which enables physicians to perform a procedure similar to traditional restrictive obesity surgeries, but without surgical incisions. The TOGA system is a set of flexible staplers designed to be inserted transorally into the stomach using endoscopic guidance. A pouch is created in the stomach that reduces its capacity by stapling anterior-to-posterior tissue to form the pouch.
Satiety used the TOGA procedure on 220 patients in a pilot trial which showed good weight loss data. The company expects to shortly complete enrollment in a 303-patient, multi-center, randomized and sham-controlled pivotal trial being conducted at nine centers in the U.S. and one outside the country.
Satiety plans to submit a PMA to the FDA in the third or fourth quarter of 2010. The company needs to show that 60% of the patients had at least a 25% excess weight loss after one year.
USGI Medical (San Clemente, California) is developing an Incisionless Operating Platform (IOP) for use in the treatment of obesity, as well as natural orifice and single-port GI procedures such as gall bladder removal and treatments for GI cancer, gastrogastric fistulas and gastroesophageal reflux disease.
The company received 510(k) clearance in 2007 for devices used in endolumenal procedures. They include expandable tissue anchors, the g-Prox tissue grasper and approximation device, and a variety of endosurgical tissue graspers. The products have been used in more than 250 clinical surgeries in the U.S., with no significant adverse events. The company believes that its tissue anchoring system is more durable for treating obesity than traditional stapling or suturing.
The IOP enables surgeons to perform revision or primary surgery through the patient's mouth, thereby eliminating the need for external incisions in the body and reducing post-op complications. Operating endolumenally offers the promise of faster healing, less scarring and less pain which should lead to quicker recovery.
The company's initial focus is on bariatric surgery but it is moving towards more general use in obesity/metabolic surgery. The principal challenges for incisionless surgery are to create a sensation of feeling for the surgeon and to attain a durable endolumenal wound closure after anatomical reconfiguration. The GI tract is very resistant to reconfiguration.
A projected 30% to 40% of patients undergoing Roux-en-Y gastric bypass procedures will regain weight after five years and an estimated 250,000 gastric bypass patients will need revision surgery by 2014.
Silhouette Medical (Prunedale, California) is developing minimally invasive technologies for appetite suppression and digestion changes as a mechanism for inducing weight loss and potentially reducing the onset of Type 2 diabetes.
Its first product, nObese, is a patented non-surgical, non-implantable 45-minute outpatient procedure weight control system. A balloon with embedded electrodes is introduced into the stomach and air inflated. RF energy is then applied to thermally modify targeted sites within the stomach.
Certain hormonal receptors are affected which reduces the appetite response without interfering with absorption of essential nutrients. In addition, the targeted areas of the stomach shrink which decreases its elasticity and ability to expand. Both processes contribute to a feeling of satiety sooner while eating. The company plans to start clinical trials in Australia in August in the second half of 2009.
EndoSphere (Redwood City, California) is clinically testing an endoscopically implanted device that assists patients in losing weight and controlling Type 2 diabetes. The device is an intestinal/duodenal restrictive implant that is about 25 cm long and is placed in the duodenum and antrum. The C-shaped, self-anchoring implant restricts flow through this area, thereby increasing contact between the digesting food and the receptors of the duodenum.
This physiological device approach to weight loss is believed to create a feeling of satiety with a smaller volume of food and to help regulate glucose production. About 15 hormones are involved in satiation. A feasibility study was conducted on 11 patients. They felt no sensation of the implant and all patients lost weight. A clinical trial outside the U.S. is being planned.