Inhalable insulin

Inhalable insulin was introduced in mid-2006 as a new method of delivering insulin, a drug used in the treatment of diabetes, to the body. All other insulin formulations are administered by subcutaneous injection.^[1]

The first such product to be marketed was Exubera, a powdered form of recombinant human insulin, delivered through an inhaler into the lungs where it is absorbed.^[2][3][4] Once it has been absorbed, it begins working within the body over the next few hours. Diabetics still need to take a longer acting basal insulin by injection.^[5]

A systematic review concluded that inhaled insulin "appears to be as effective, but no better than injected short-acting insulin. The additional cost is so much more that it is unlikely to be cost-effective."^[6] In October 2007, Pfizer announced that it would be discontinuing the production and sale of Exubera due to poor sales.^[7] Several other companies are developing inhaled forms of the drug to reduce the need for daily injections among diabetics.

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History

Insulin was introduced by Banting and Best in 1921 as an injectable agent. German researchers first introduced the idea of inhalable insulin in 1924.^[1] Years of failure followed until scientists realized they might be able to use new technologies to turn insulin into a concentrated powder with particles sized for inhalation.^[1]

This technology was developed so that the inhaled insulin can effectively reach the lung capillaries where it is absorbed.^[8] Nektar Therapeutics of San Carlos, California developed this technology that paved the way for pharmaceutical companies to begin testing and formulating inhalable insulin.^[1] Once concrete methods were developed, human tests began in the late 1990s.^[1] In January of 2006, the FDA approved the use of Exubera which is a form of inhalable insulin developed by Pfizer.^[2]

Approval and competing drug development

Exubera is the brand name of first formulation of inhalable insulin to receive the US Food and Drug Administration (FDA) approval.^[2] It is manufactured by Pfizer in collaboration with Nektar Therapeutics and is licensed for use by both type 1 and type 2 diabetics. However in the UK its use in under the National Health Service "should not be recommended because it could not be proven to be more clinically or cost effective than existing treatments",^[5] except under special circumstances.^[9] In April of 2006, the UK's National Institute for Health and Clinical Excellence issued a preliminary statement advising against the use of inhalable insulin on the grounds that the benefits of avoiding injections did not justify the higher cost of the new product, estimated at $49.95 per year. At that time, NICE recommended use of the new drug only in clinical trials.^[10]

Concerns have been expressed by the Institute for Safe Medication Practices about a serious risk of dosing errors when prescribing Exubera.^[11] Insulin is traditionally prescribed in international units, but Exubera is prescribed in milligrams. 1 mg of Exubera is equivalent to 3 units of insulin, however, the increment is not linear: 3 mg of Exubera is equivalent to 8 units of insulin and not 9 units as might be expected, and the prescriber is strongly advised to refer to the manufacturer's conversion table before prescribing. Furthermore, because of retention of blister contents, three consecutive doses of 1mg blisters of Exubera results in a higher dose of insulin than a single 3mg blister of Exubera, further complicating prescribing calculations.

Exubera is considered a short or rapid acting insulin. In clinical studies, Exubera reached peak concentration levels faster than some insulins administered by injection.^[2] Thus, this form of insulin would begin working within the body faster than insulin that is injected. Type 1 and 2 diabetics will still need an injection of longer acting insulin to maintain a basal level for a 24 hour period.^[5]

As of October 18, 2007, Pfizer has announced that it will no longer manufacture or market Exubera. According to Chairman and CEO Jeffrey Kindler this is because Exubera "failed to gain acceptance among patients and physicians."^[7]

As of October 2007, there are competing inhalable forms of insulin that are in development or in phase III clinical trials, but yet to receive FDA approval for sale and use by diabetics. These include Alkermes working with Eli Lilly and Company,^[12] MannKind Corporation,^[13],^[14] and Aradigm working with Novo Nordisk.

Pfizer patent infringement lawsuit

Novo Nordisk, a Danish diabetes pharmaceutical company and Pfizer competitor, filed suit against Pfizer on August 1, 2006, claiming patent infringement.^[15][16] The lawsuit seeks both compensatory damages and injunctive relief. Novo sought a preliminary injunction preventing the release of Pfizer's planned September 2006 launch of the diabetes drug. A federal judge, however, delayed any decision on Novo Nordisk's request for injunctive relief until at least December 4, 2006 when a court hearing is scheduled in the case.^[17] Pfizer's answer contends that Novo wants to deny diabetics access to Exubera, the only FDA approved inhaled insulin, and interfere with the company's pharmaceutical business.^[18]

On December 14, 2006 a federal judge denied Novo Nordisk's request for a preliminary injunction to halt sales of Pfizer's inhaled insulin.^[19] The patent lawsuit, however, has not been dismissed, and Pfizer's legal defenses are preserved. The pharmaceutical companies are still litigating in court over their respective inhaled insulin patent claims, a process that could take some time to resolve.

References