Diabetes is the fourth leading cause of death worldwide and accounts for $286 billion in annual healthcare costs. Globally, 194 million people suffer from diabetes and this number is rising rapidly. For these patients, a regular regimen of pills or injectable insulin is necessary to control blood-glucose levels and to minimize the chance of disabling and potentially deadly complications such as blindness, kidney failure, nerve damage, heart disease, and limb loss.
"Exubera" (Pfizer Inc., New York, NY,
http://www.pfizer.com/), a new treatment for adults with types 1 or 2 diabetes, is the world's first inhaled insulin. The drug, a rapid-acting human insulin made with recombinant DNA technology, was approved by the US Food and Drug Administration and the European Commission (EC) in January 2006. Expected to be available globally by mid-year, Exubera offers diabetic patients an alternative to traditional regimens and can replace injections, a delivery route often associated with poor patient compliance. Other advantages of the inhaled insulin include faster entry into the bloodstream compared with injectable insulin. Furthermore, unlike injectable insulin, the powdered form does not require refrigeration.
In studies involving more than 2500 adults, Exubera was shown to be as effective as injectable insulin in achieving glycemic control for types 1 or 2 diabetics. In adults with type 2 diabetes whose blood-glucose levels are not sufficiently controlled with commonly used oral therapies, Exubera has been shown to provide greater improvements in glycemic control. In addition, patients who took Exubera reported greater overall treatment satisfaction and acceptance compared with insulin injections or oral therapies.
Exubera is taken just before mealtimes. In patients with type 2 diabetes, Exubera can be used alone as an alternative to rapid-acting insulin injections or diabetes pills, or in combination with diabetes pills or longer acting insulin. In patients with type 1 diabetes, Exubera is used in combination with longer acting injected insulin.
Creating a powdered form of insulin that can be inhaled through the mouth into the lungs and proving it works as well or better than insulin by traditional delivery methods has taken about 20 years to develop and cost roughly $1 billion. The brainchild of John S. Patton, who cofounded Inhale Therapeutics in 1990, now Nektar Therapeutics (San Carlos, CA,
http://www.nektar.com/), Exubera has required a high degree of collaborative effort to bring it to market.
Nektar Therapeutics, a specialist in proprietary inhalation technology, developed the powdered-insulin formulation and the inhaler and has worked on the product development with Pfizer since 1994. The company, which filed the new drug application (NDA) for Exubera, initially undertook the project as a joint development program with Aventis (now Sanofi-Aventis, Paris, France,
http://www.sanofi-aventis.com/). After buying Sanofi's interest for $1.3 billion in March 2006, Pfizer is now solely responsible for the global marketing and distribution of Exubera under a license from Nektar.
The Exubera (Pfizer, New York, NY) powdered-insulin inhaler is approximately the size of an eyeglass case (second from left). To use the inhaler, the base is extended and a foil blister containing powdered insulin is inserted.
The Exubera inhaled insulin product is based on Nektar's evaporative "Pulmonary Particle Technology" that reduces particles to 2 μm, a size that can be absorbed by the alveoli in the lungs. Pfizer produces the very fine insulin powder in Frankfurt, Germany, at a plant acquired from Sanofi-Aventis. A second highly automated, state-of-the-art production facility in Terre Haute, Indiana, fills the powdered insulin in two sizes of unit-dose blister packs.