Will alternative insulin delivery make subcutaneous route obsolete?

October 1, 2004

As pharmacists well know, subcutaneous insulin injections are a major barrier to diabetes treatment adherence. The injections are typically administered several times daily for those with Type 1 disease, and twice daily in some patients with Type 2. If several alternative delivery systems in the pipeline are successful, will they make the needle obsolete in diabetes management? Only time, and the realities of the marketplace and reimbursement issues, will tell.

As pharmacists well know, subcutaneous insulin injections are a major barrier to diabetes treatment adherence. The injections are typically administered several times daily for those with Type 1 disease, and twice daily in some patients with Type 2. If several alternative delivery systems in the pipeline are successful, will they make the needle obsolete in diabetes management? Only time, and the realities of the marketplace and reimbursement issues, will tell.

These alternative delivery systems are designed to make the administration of insulin more comfortable and therefore increase compliance. One commercially available device, the Medi-Jector Vision, still injects subcutaneously but bypasses the needle.

The Medi-Jector, manufactured by Antares Pharma, involves a pen-like syringe with preloaded insulin. The patient loads the syringe with the type of insulin he or she is prescribed and dials the correct dose. When the pen is pressed on the selected injection site, such as the forearm or thigh, the Medi-Jector releases a jet stream of insulin through a small orifice, and the insulin is deposited subcutaneously. According to Roger Harrison, CEO of Antares, the velocity of the jet stream allows it to penetrate the skin without using a needle.

In development Other therapies in development include an insulin spray that is identical in form to the metered-dose inhalers used to treat asthma, but lacking the inhalation step, and an insulin tablet that patients simply swallow.

The buccal spray formulation, being developed by Generex Biotechnology, based in Toronto, delivers insulin to the buccal cavity as a fine spray, using the company's RapidMist device.

"Our buccal insulin spray product is being developed for the treatment of both Type 1 and Type 2 diabetes," said Fabio Chianelli, manager of business development at Generex. "The product, known as Oralin, is currently in phase II-B clinical trials." However, the sojourn through the regulatory hoops will probably put commercial availability several years away, he said.

The company decided that patients would likely accept the metered-dose spray, since metered-dose inhalers for the treatment of asthma are ubiquitous.

However, the patient does not inhale with the buccal spray devices. Instead, the drug is sprayed onto the buccal mucosa. From there, the high-speed spray allows the drug to be rapidly absorbed into the bloodstream. The deposition of the drug onto the buccal mucosa also allows the developers to bypass earlier concerns about any risks to lung tissue that have been raised regarding investigative inhaled insulin formulations, Chianelli explained.

The pill form of insulin being developed by Emisphere Technologies is one of several therapies the company has in the pipeline. The firm's mission is to identify ways of delivering oral therapies that historically have required injection or inhalation. Steve Dinh, VP for research and technology development, discussed the company's investigational oral insulin formulation.

"We have demonstrated that we can deliver insulin orally in healthy volunteers, and in patients with Type 1 and Type 2 diabetes," Dinh said. "The study involving healthy volunteers was a proof-of-concept study." In that study, the investigators were able to show that the insulin was delivered systemically and that the volunteers had a corresponding drop in glucose.

"In that study, we were also able to show that c-peptides, a marker for spontaneously produced insulin, were turned off," he added. "In other words, the insulin that was measured came from exogenous insulin." Therefore, he said, the proof-of-concept study showed that insulin can be delivered orally in a tablet form and that it is biologically active.

"The studies involving people with Type 1 and Type 2 diabetes were intended to determine whether insulin delivered orally is effective in managing such patients' disease," he added. "With Type 1 disease, because patients do not produce insulin at all, any detection of insulin would mean that it came from the orally delivered drug." In the Type 2 studies, the investigators were able to demonstrate that their oral insulin formulation could mimic the first-phase insulin response seen with conventional insulin therapy.