Holding Their Breath: Inhaled Insulin - Pharmaceutical Executive


Holding Their Breath: Inhaled Insulin
Exubera, Pfizer's inhaled-insulin therapy, is carving out a new market for diabetes drugs. Four more companies are looking for their share.

Pharmaceutical Executive

Ultimately, Mannkind's product may be the only one to change the way doctors think about diabetes, says Skyler, who has been a paid consultant for all of the companies with products discussed in this article. "Mannkind may demonstrate that there really is a way to deliver a burst of insulin very quickly, because it doesn't take that much to shut down the liver. That's the only place where I see these products having a real difference in metabolism as opposed to a difference in convenience, so far."

Kos and Novo Nordisk/Aradigm have developed liquid formulas. "The difference to most other formulations is that we are basing it on the same paradigm as asthma devices," said Kos Pharmaceutical's Rosskamp. "Asthma formulations just contain the propellant plus the actual drug, which usually is a steroid or another drug. So ours is only the propellant—HFA, which is a [environmentally] friendly gas—plus the insulin [and a little water]. If you really want to say it correctly, they are in a suspension form. But I think aerosol liquid would also be the right way to characterize it."

Rosskamp also emphasizes that Kos's insulin contains no additives or preservatives, which in his view differentiates it from the powders, which contain non-insulin excipients or preservatives.

NovoNordisk and Aradigm, on the other hand, begin with a powder that is heated with liquid in the chamber of the inhaler and drawn through laser-drilled holes that are one micron in diameter. This creates an aerosol mist of two-to three-micron droplets.

The Device

Next to formulation, the convenience, reliability, and size of the inhaler are likely to be among the key factors driving patient demand.

"We know from Pfizer's reports and also from various photographs that Exubera has a reasonable- size device," said Jane Kidd, principal analyst with Wood Mackenzie in Edinborough, Scotland. The Pfizer inhaler folds to roughly the size of an eyeglass case, but extends to about 10 inches in length when in use. "Anybody that can come onto the market with a delivery device that is smaller, easier to use, easier to maintain, possibly disposable—but that can ensure the patient will have good delivery of the insulin—will be in a far more favorable position than Pfizer."

But at least one inhaler could succeed with precision dosing. Trials may confirm that the Novo Nordisk inhaler can titrate doses to one unit of insulin, which is a level of precision usually associated with injected insulin, but finer than the three-unit dosages typical of the Exubera and Lilly/Alkermes devices. This, at least, was the goal originally proposed by Aradigm.

"Theoretically they can titrate to one unit," says Skyler. "Novo Nordisk also has a lot of bells and whistles to assure safety. They've gone out and built a Rolls-Royce. They function as well as a Rolls-Royce in relation to other vehicles, but there's not a big market for the Rolls-Royce." Aradigm referred questions about the system to Novo Nordisk, which declined repeated requests for an interview, noting in an e-mail only that "we expect to confirm reinitiation of our Phase III clinical trials during Q1 2006." Sources suggest that the trials were suspended for a pharmacokinetic/pharmacodynamic-dosing study.

In general, inhalers are shaping up to be smaller than Pfizer's. Because Lilly/Alkermes relies on the lightness of the particle, it was able to create a small inhaler powered by the patient's breath. Lilly's marketing materials describe the inhaler as about the size of a highlighter. A capsule of insulin powder is placed into the inhaler and broken open when the inhaler is compressed. At that point, the patient draws air through the inhaler to propel insulin particles into the lungs. According to Alkermes, the insulin enters the mouth early in the breath, so that the full dose is achieved even with a relatively small breath.


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