No More Insulin Shots: Pills, Skin Patch, Mouth Spray, Inhalants on Horizon for People with Diabetes

6/17/2002

From: Diane Tuncer, 703-299-5510 Mark Overbay, 703-549-1500, ext 2290 Newsroom June 14-18: Room 220, Moscone Center, San Francisco, Calif., 415-978-3733

SAN FRANCISCO, June 17 -- The decades-long dream of people with diabetes -- insulin without injections -- is about to come true, according to reports here Sunday at the American Diabetes Association's 62nd Annual Scientific Sessions. Research success has been achieved with multiple options, some of which may complement each other -- a simple pill, a transdermal skin patch, a mouth spray, and several versions of pulmonary inhaled insulin.

Of the more than 17 million Americans, it is estimated that 3.7 million must take one to five insulin shots daily to control their disease. Diabetes is a group of serious diseases characterized by high blood sugar levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as blindness, kidney disease, heart disease and amputations. It is the fifth leading cause of death by disease in the U.S.

THE INSULIN PILLS

Considerable interest at the meeting focused on reports of the first two oral pills shown to work in humans.

"In the past, an insulin pill was useless because the molecule was too large to get through the membrane in the gut or was degraded there," said Richat Abbas, Ph.D., director of Biopharmaceutics, Emisphere Technologies, in a recent interview. The company's oral delivery agent facilitates absorption to the liver and then the systemic circulation with maximum insulin concentrations seen within 15 to 25 minutes, thus mimicking the physiological production and excretion of insulin from the pancreas. In a Phase I study evaluating the safety and tolerability of the capsule, neither a plain insulin pill nor the delivery agent alone had any impact on insulin levels; however, insulin combined with the delivery agent provided insulin absorption at clinically significant levels.

Hexyl-Insulin Monoconjugate (HIM2), developed by Nobex Corporation, in conjunction with GlaxoSmithKline, was another insulin pill presented at the meeting and is now in Phase II clinical trials. It utilizes patented polymer technology to resist enzymatic degradation of the hormone and promote its absorption into the bloodstream. "HIM2 yielded maximum absorption when taken 15 minutes before a meal," reported Stephen Clement, M.D., associate professor of medicine at Georgetown University, Washington, D.C. HIM2 yielded insulin-lowering benefits equal to injected insulin when multiple doses were given over a three-day period.

THE SKIN PATCH

The skin patch involves a two-step process, according to Alan Smith, Ph.D., Vice President of Research of Altea Development Corporation. First, an electronic adhesive patch, powered by a small battery, is applied to the skin; in a millisecond, it painlessly vaporizes cells on the skin surface, creating microscopic openings. Then a small patch, containing a reservoir of insulin, is applied to the skin, just like a Bandaid(tm). Altea's research has shown that insulin is steadily absorbed into the body during 12 hours of wear. The company is now working on a 24-hour version. The patch will use "off the shelf" insulin, meaning only the delivery system requires government approval; that may accelerate its arrival in the marketplace.

MIXING THE NEW OPTIONS

However, the patch only delivers the "basal" -- or basic -- level of insulin a person needs throughout the day and night. In contrast, the pills provide the "bolus" -- extra dose -- needed at mealtimes. The oral spray and inhaled insulin also can provide such a bolus.

THE ORAL SPRAY

"The Rapid Mist device looks like the metered dose inhalers used by people with asthma, but it has been modified so that Oralin, a liquid aerosol version of insulin, is absorbed by the mucous membranes in the cheeks, tongue, and throat," explained Pankaj Modi, Ph.D., M.B.A., vice president of Research and Development at Generex Biotechnology Corporation. Research presented here showed that the benefit from Oralin was identical to an insulin injection in its ability to lower blood glucose levels. Further, Oralin was able to serve as the mealtime boost needed by some people who are failing oral hypoglycemic drugs.

The company is also working on a product, now in Phase I testing, that would provide basal day and night coverage.

THE INHALED INSULINS

Multiple reports of research success with pulmonary insulins were made, and Jay S. Skyler, MD, Professor of Medicine, Pediatrics, and Psychology at the University of Miami, provided an overview of all of them: Exubera by Inhale Therapeutics, Pfizer, and Aventis; AERx by Aradigm and Novo Nordisk; Insulin Technospheres by Mannkind/PDC; AIR System by Alkermes with Eli Lilly; and Aerodose by Aerogen with Disetronic.

"All are in development and have different features, but basically these systems deliver a dose of insulin-in liquid or dry powder form-through the mouth, directly into the lungs, where it enters the blood circulation as a rapid-acting insulin," explained Dr. Skyler.

He emphasized that the research must now determine whether the pulmonary route is safe, cost-effective, and viable for long-term insulin delivery.

All of the products are at least several years away from government approval and marketing.

The American Diabetes Association is the nation's leading voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities.