While last week’s abandonment of Exubera by Pfizer (New York) is a setback for those who had hoped for easier administration of insulin, it is unlikely to be a death knell for this effort. Several companies are still pursuing the delivery of insulin since this remains the most important possible alternative to the use of daily “needlesticking” to manage glucose control.

Following are some of those efforts.

• Baxter Healthcare (Deerfield, Illinois) is developing the use of microsphere technology administered via what it has called a “small, standard dry powder inhaler.” In April the company reported results of a Phase I study that evaluated pulmonary insulin produced with Promaxx microsphere technology, demonstrating that the insulin powder can be administered to the deep lung using an off-the-shelf dry powder inhaler designed for upper airway drug delivery.

Study subjects received doses of 10 International Units of insulin through subcutaneous injection (SC) in one period, and 6.5 milligrams of the inhaled insulin microspheres, called recombinant human insulin inhalation powder (RHIIP) in the other period. Study data show that RHIIP had a faster onset of action than SC. The bioavailability of RHIIP relative to SC was more than 12%.

• Novo Nordisk (Bagsvaerd, Denmark) is developing the AERx Diabetes Management System (iDMS) and is in a Phase III trial program. In mid-2006, it obtained patent rights for the system’s inhaler delivery device from Aradigm (Hayward, California) for $27.5 million, providing a key element to push forward system development.

The companies first developed a partnership to develop iDMS in 1998, but in 2004 the effort was stalled as a result of trial difficulties. Novo then bought out the development and manufacturing rights to the system, with execution of those rights in early 2006. With patent rights for the inhaler acquired, Novo has restarted the Phase III trial.

Aradigm retains patent rights for the delivery system outside glucose control.

• Eli Lilly (Indianapolis) and Alkermes (Cambridge, Massachusetts) are working to develop inhaled insulin using the AIR Inhaled System from Alkermes. The companies have released data on safety studies that they hope will position their product for both diabetes and breathing problems such as asthma and chronic obstructive pulmonary disease.

• MannKind (Valencia, California) is developing Technosphere Insulin (TI) and is in two Phase III studies designed “to confirm the sustained efficacy” of the product. Both randomized trials are scheduled to last a year.

The first, Study 009, will include 500 Type I patients and compare TI to subcutaneous injections of a rapid-acting insulin analogue. Patients in both arms also will receive a basal insulin regimen. The second, Study 102, is the subject of a special protocol assessment by the FDA. It will include 500 Type 2 patients and compare TI plus basal insulin to subcutaneous injections of premixed insulin, including a rapid-acting insulin analogue.

The company says that Technosphere technology creates particles with a “unique pharmacokinetic profile,” leading to quicker insulin absorption rate than that seen with other insulin products, injectable and inhaled.

• Kos Pharmaceuticals (Cranbury, New Jersey) — now owned by Abbott Laboratories (Abbott Park, Illinois) — has been in an effort to deliver insulin by means of an aerosolized liquid by means of a device similar to a standard asthma rescue inhaler. This type of inhaler is held in the palm and so much easier to use than the inhaler required to deliver Exubera.

— DON LONG