New Technologies Chip Away at Injectible Drug Delivery
Contents
Seeking an Alternative to Injection
Something New in Oral Delivery
Insulin Inhaler Is as Effective as Injections
Seeking an Alternative to Injection (Back to Top)
With more and more products from biotechnology entering the marketplace, the old fashioned "shot"—injected drug delivery—is here to stay. Proteins, peptides, and peptide-like drugs don't generally survive the gut, so oral delivery is out. Moreover, these materials absorb poorly through the skin, so forget about creams and ointments. Nevertheless, the problems with injectible drugs—safety, poor compliance, need to visit a doctor or nurse, and stability of the drug itself—will not go away. Hence the lure of alternatives to injection by needle.
Masking technologies, e.g. liposomes, have proven of limited value in protecting proteins delivered orally. Several firms, among them Medi-Ject (Minneapolis) and BioJect (Portland, OR), offer needle-free injection systems that propel drugs through the skin rather than depositing them through a needle. Companies such as Iomed (Salt Lake City, UT), EMPI (St. Paul, MN), and Genometrics (San Diego) are being courted by large pharmaceutical firms for their electrically-enhanced transdermal delivery technologies, of which iontophoresis is the best example. Although less painful and requiring less expertise to use than a needle, electrically-enhanced transdermal delivery will probably suffer from significantly lower compliance than pills/tablets, which may be as low as 60%.
Still, the pharmaceutical industry remains enamored with new delivery technologies. The ability to get strange-looking active materials into the body greatly expands what is possible at the discovery stage. Later on, novel delivery systems almost painlessly extend the proprietary market position of soon-to-be-off-patent (and some generic) drugs. Frost and Sullivan (Mountain View, CA) estimated US markets for drug delivery products and technologies at $5.2 billion in 1998, and forecasts double-digit growth for this industry segment for the next several years. Frost and Sullivan points out that markets for new drug delivery technologies are driven by the increasing rate at which biotech compounds are being discovered.
Something New in Oral Delivery (Back to Top)
One strategy for making peptides orally available involves amidating the terminal residue to make the drug "foreign" to digestive peptides. According to theory, since most of the drug survives the digestive system, some should wind up in the blood. Unigene Laboratories (Fairfield, NJ) discovered several years ago that when taken orally, amidated calcitonin (an anti-osteoporosis drug) winds up in the bloodstream, where the peptide is deamidated to calcitonin. On June 21, Unigene was awarded US Patent 5,912,014, which locks up calcitonin peptide amidation for the company (and partner Warner-Lambert), and with it a US market for safe osteoporosis prevention worth at least $500 million. Unigene has filed additional patent applications for similarly modifying other peptide hormones, hoping this approach will open up a new era in oral drug delivery.
Insulin Inhaler Is as Effective as Injections (Back to Top)
Also on June 21, but a continent away, Aradigm Corp. (San Diego) announced startling clinical results showing that insulin inhaled via its proprietary AERx Diabetes Management System immediately before a meal achieved glucose control comparable to regular insulin injected 30 minutes before mealtime. The study results, from the company's first phase II US trial, were released this week at the American Diabetes Association's 59th Annual Scientific Sessions.
The study, involving 20 adult, insulin-dependent (Type 1) diabetes patients, compared the glucose-lowering effects of inhaled insulin delivered via the AERx System to those of subcutaneous insulin injections. Inhaled insulin was given immediately prior to a test meal, while subcutaneous regular insulin was dosed 30 minutes before the meal. There was no statistical difference in glucose control between the delivery methods. Other measurement parameters, such as total change in glucose and time to maximum glucose effect, were also found not to be statistically different.
The AERx Diabetes Management System produces fine aerosol mists of insulin that are deposited deep into the lung for absorption into the bloodstream. The hand-held "electronic inhaler" guides the patient to breathe correctly and consistently every time, automatically delivering the drug at the right point during the inhalation. Aradigm is developing the AERx Diabetes Management System in collaboration with Novo Nordisk A/S of Denmark.
For more information: Ronald Levy, President, Unigene Inc., 110 Little Falls Rd., Fairfield, NJ 07004. Tel: 973-882-0860. Fax: 973-227-6088. Bikash Chatterjee, VP of Operations, Aradigm Corp., 3929 Point Eden Way, Hayward, CA 94545. Tel: 510-265-9000. Fax: 510-265-0277.
By Angelo DePalma