Inhalable insulin
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Inhalable insulin is a powdered form of
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, delivered with an inhaler into the lungs where it is absorbed. In general inhaled insulins have been more rapidly absorbed than subcutaneous injected insulin, with faster peak concentration in serum and more rapid metabolism. Exubera, developed by Inhale Therapeutics (later named
Nektar Therapeutics Nektar Therapeutics (Nektar) is an American biopharmaceutical company. The company was founded in 1990 and is based in San Francisco, California. The company develops new drug candidates by applying its proprietary PEGylation and advanced polymer ...
), became the first inhaled insulin product to be marketed, in 2006 by
Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
, but poor sales led Pfizer to withdraw it in 2007. Afrezza, a
monomeric In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Mo ...
inhaled, ultra rapid-acting insulin developed by Mannkind, was approved by the FDA in 2014 and is the only inhaled insulin comercialized at the moment. __TOC__


History

Insulin was discovered by Sir Frederick G Banting, Charles H Best, and JJR Macleod from the
University of Toronto The University of Toronto (UToronto or U of T) is a public research university in Toronto, Ontario, Canada, located on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution ...
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 Nektar Therapeutics (Nektar) is an American biopharmaceutical company. The company was founded in 1990 and is based in San Francisco, California. The company develops new drug candidates by applying its proprietary PEGylation and advanced polymer ...
developed technology to make insulin into small particles, technology then licensed to Pfizer. Alkermes developed a delivery device that they licensed to
Eli Lilly and Company Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...
. Once concrete methods were developed, human tests began in the late 1990s. In January 2006, the
U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) approved the use of Exubera, a form of inhalable insulin developed by
Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
. It was approved in the UK in August 2006 but reimbursed by the
National Health Service The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...
only for people who had problems with needles. It was not reimbursed by any US insurer. A 2007
systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
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." 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 Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...
, MannKind Corporation, and Aradigm working with
Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
. By March 2008, except for MannKind's Afrezza product, all of these products had been discontinued because investors all decided to withdraw funding. On March 16, 2009 MannKind submitted a new drug application for their inhalable insulin. In 2011 the FDA denied approval of Afrezza; because the design of the delivery device had changed, it requested additional clinical trials 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 2014 Mannkind and Sanofi agreed that Sanofi would take over manufacturing and marketing of Afrezza, but Sanofi said it was dropping the effort in January 2016 due to poor sales of $7.5 million in 2015; the companies formally terminated the agreement in November 2016. At the time that Sanofi announced it was dropping the product Mannkind said it would continue alone, and it had taken over manufacturing and relaunched the drug by July 2016. According to results presented at the 2018 meeting of the American Diabetes Association (ADA), Afrezza increases the time that blood glucose levels remain in optimal range (74 – 106 mg/dl), reducing both spikes in blood glucose and time in hypoglycemia in adults with Type I diabetes, compared to insulin Aspart.


References

{{Oral hypoglycemics and insulin analogs Insulin therapies Pfizer brands Sanofi Withdrawn drugs