Inhalable insulin is a powdered form of insulin, delivered with a nebulizer into the lungs where it is absorbed. A 2007 systematic review concluded that the inhaled hexameric insulin (Exubera) "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."
Exubera, developed by Inhale Therapeutics (later named Nektar Therapeutics), became the first inhaled insulin product to be marketed in 2006 by Pfizer, but poor sales led Pfizer to withdraw it in 2007. Afrezza, a monomeric inhaled insulin developed by Mannkind, was approved by the FDA in 2014.
Insulin was introduced by Banting and Best from the University of Toronto in 1921 as an injectable agent. German researchers first introduced the idea of inhalable insulin in 1924. 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.
In the 1980s Nektar Therapeutics developed technology to make insulin into small particles that they licensed to Pfizer; Alkermes developed a delivery device that they licensed to Eli Lilly and Company.
Once concrete methods were developed, human tests began in the late 1990s. In January 2006, the U.S. Food and Drug Administration (FDA) approved the use of Exubera, a form of inhalable insulin developed by Pfizer; it was approved in the UK in August 2006 but reimbursed by the National Health Service only for people who had problems with needles. However, in 2007, Pfizer announced that it would no longer manufacture or market Exubera. According to Chairman and CEO Jeffrey Kindler this was because Exubera "failed to gain acceptance among patients and physicians".
At the time of Exubera's discontinuation, several other companies were pursuing inhaled insulin including Alkermes working with Eli Lilly and Company, MannKind Corporation, and Aradigm working with Novo Nordisk. By March 2008, all of these products had been discontinued except for MannKind's Afrezza product.
On March 16, 2009 MannKind submitted an NDA for their inhalable insulin. In 2011 the FDA denied approval of Afrezza and requested additional clinical trials to its product, the design of which had changed, to ensure that people would use it the same way as the earlier versions. After conducting further studies, Mannkind submitted a new application, and in June, 2014, the FDA approved Afrezza for both Type I and Type II adult diabetics, with a label restriction for patients having asthma, active lung cancer or COPD.
In June of 2016, Mannkind entered into a collaboration agreement with JDRF (formerly known as Juvenile Diabetes Research Foundation) to focus on the use of Afrezza in the pediatric population. During the American Diabetes Association's Annual meeting (ADA 2016) later that month, Mannkind presented 6 abstracts, one of which was late-breaking data demonstrating faster onset and shorter duration of action compared to mealtime insulins.
Mannkind Corporation launched their own U.S. sales force during the last week of July, 2016. Consisting of about 70 people initially, including management, the establishment of a direct sales team by Mannkind marked the transition from a terminated global distribution arrangement with French pharmaceutical giant, Sanofi. Mannkind also took over responsibility for sales outside the U.S. According to Michael Castagna, Mannkind's Chief Commercial Officer, the U.S. sales team for Afrezza will initially focus on physician and nurse education due to the critical differences between inhaled Technosphere insulin and current rapid-acting injected insulin analogs.
- Black C, Cummins E, Royle P, Philip S, Waugh N (2007). "The clinical effectiveness and cost-effectiveness of inhaled insulin in diabetes mellitus: a systematic review and economic evaluation". Health technology assessment (Winchester, England). 11 (33): 1–126. PMID 17767897.
- "FDA Approves First Ever Inhaled Insulin Combination Product for Treatment of Diabetes" (Press release). Silver Spring, Maryland: FDA. 2006-01-27.
- John Simons (19 October 2007). "How the Exubera debacle hurts Pfizer". CNNMoney. Retrieved 2007-10-21.
- "FDA approves Afrezza to treat diabetes" (News Release). U.S. Food and Drug Administration. June 27, 2014. Retrieved July 19, 2016.
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- "Alkermes Inc. AIR Inhaled Insulin System Human insulin inhalation powder Began Phase III trial to evaluate effectiveness in improving glucose control vs. injected premeal insulin in 400 patients 4/06 Type II diabetes". Bioworld Today. January 1, 2007. Retrieved 2007-10-22.
- "Technosphere Insulin - How it works". MannKind Corp. 2007. Archived from the original on 2007-10-20. Retrieved 2007-10-22.
- Pollack, Andrew (November 16, 2007). "Betting an Estate on Inhaled Insulin". The New York Times. Retrieved May 5, 2010.
- Lilly/Alkermes—RIP, AIR Insulin, Close Concerns, Inc. Company Watch, Diabetes Close Up #78, www.diabetescloseup.com.
- "MannKind Corporation Receives Complete Response Letter from the FDA for AFREZZA(R)". MannKind Corporation. January 19, 2011. Retrieved July 19, 2016.
- "Highlights of Prescribing Information" (PDF). MannKind Corporation. Archived from the original (PDF) on August 1, 2014.
- "MannKind Announces Late-Breaking Data Demonstrating Faster Onset and Shorter Duration of Action Compared to Mealtime Insulins". MannKind Corporation. June 12, 2016. Retrieved July 19, 2016.
- Kam, Ken. "MannKind Will Market Afrezza Better Than Sanofi Ever Did". Retrieved 2016-07-31.