Medicine:Inhalable insulin

From HandWiki
Short description: Powdered insulin delivered with an inhaler

Inhalable insulin is a powdered form of insulin, delivered with an inhaler into the lungs where it is absorbed.[1] In general inhaled insulins have been more rapidly absorbed than subcutaneous injected insulin, with faster peak concentration in serum and more rapid metabolism.[2]

Exubera, developed by Inhale Therapeutics (later named Nektar Therapeutics), became the first inhaled insulin product to be marketed, in 2006 by Pfizer,[3] but poor sales led Pfizer to withdraw it in 2007.[4] Afrezza, a monomeric inhaled, ultra rapid-acting insulin developed by Mannkind, was approved by the FDA in 2014 and is the only inhaled insulin commercialized at the moment.[5]

History

Insulin was discovered by Sir Frederick G Banting, Charles H Best, and JJR Macleod from the University of Toronto in 1921 as an injectable agent.[6] German researchers first introduced the idea of inhalable insulin in 1924.[7] 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.[citation needed]

In the 1980s Nektar Therapeutics 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.[7]

Once concrete methods were developed, human tests began in the late 1990s.[7] In January 2006, the U.S. Food and Drug Administration (FDA) approved the use of Exubera, a form of inhalable insulin developed by Pfizer.[3] It was approved in the UK in August 2006 but reimbursed by the National Health Service only for people who had problems with needles.[8] It was not reimbursed by any US insurer.[9] 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."[10] 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".[4]

At the time of Exubera's discontinuation, several other companies were pursuing inhaled insulin including Alkermes working with Eli Lilly and Company,[11] MannKind Corporation,[12][13] and Aradigm working with Novo Nordisk. By March 2008, except for MannKind's Afrezza product, all of these products had been discontinued because investors all decided to withdraw funding.[14]

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.[15] 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.[5][16] In 2014 Mannkind and Sanofi agreed that Sanofi would take over manufacturing and marketing of Afrezza,[17] but Sanofi said it was dropping the effort in January 2016 due to poor sales of $7.5 million in 2015;[18] the companies formally terminated the agreement in November 2016.[19] At the time that Sanofi announced it was dropping the product Mannkind said it would continue alone,[18] and it had taken over manufacturing and relaunched the drug by July 2016.[19] 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.[20]

References

  1. ↑ Neumiller, Joshua (June 2010). "Pharmacologist". Annals of Pharmacotherapy 1231-9 (44): 7. https://www.researchgate.net/publication/44643382. 
  2. ↑ "Making Insulin Accessible: Does Inhaled Insulin Fill an Unmet Need?". Advances in Therapy 33 (8): 1267–78. August 2016. doi:10.1007/s12325-016-0370-1. PMID 27384191. 
  3. ↑ 3.0 3.1 "FDA Approves First Ever Inhaled Insulin Combination Product for Treatment of Diabetes" (Press release). Silver Spring, Maryland: FDA. 2006-01-27.
  4. ↑ 4.0 4.1 Simons, John (19 October 2007). "How the Exubera debacle hurts Pfizer". CNNMoney. https://money.cnn.com/2007/10/19/magazines/fortune/simons_pfizer_erbitux.fortune/index.htm?postversion=2007101916. 
  5. ↑ 5.0 5.1 "FDA approves Afrezza to treat diabetes". U.S. Food and Drug Administration. June 27, 2014. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm403122.htm. 
  6. ↑ "100 Years of Insulin". https://www.diabetes.org.uk/research/research-impact/insulin#:~:text=Insulin%20was%20discovered%20by%20Sir,than%20a%20year%20or%20two.. 
  7. ↑ 7.0 7.1 7.2 Gillis, Justin (January 28, 2006). "Inhaled Form of Insulin Is Approved". The Washington Post. https://pqasb.pqarchiver.com/washingtonpost/access/977402861.html?dids=977402861:977402861&FMT=ABS&FMTS=ABS:FT&fmac=&date=Jan+28%2C+2006&author=Justin+Gillis&desc=Inhaled+Form+of+Insulin+Is+Approved. 
  8. ↑ "Inhaled insulin given UK launch". BBC News. August 4, 2006. http://news.bbc.co.uk/2/hi/uk_news/england/5245344.stm. 
  9. ↑ "Commentary: Why Was Inhaled Insulin a Failure in the Market?". Diabetes Spectrum 29 (3): 180–4. August 2016. doi:10.2337/diaspect.29.3.180. PMID 27574374. 
  10. ↑ "The clinical effectiveness and cost-effectiveness of inhaled insulin in diabetes mellitus: a systematic review and economic evaluation". Health Technology Assessment 11 (33): 1–126. September 2007. doi:10.3310/hta11330. PMID 17767897. 
  11. ↑ "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. http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?forceid=413&next=bioWorldPhaseIII_searchDetails&search=1&htsid=0&htmax=1. [|permanent dead link|dead link}}]
  12. ↑ "Technosphere Insulin - How it works". MannKind Corp. 2007. http://www.mannkindcorp.com/how-technosphere-work.aspx. 
  13. ↑ Pollack, Andrew (November 16, 2007). "Betting an Estate on Inhaled Insulin". The New York Times. https://www.nytimes.com/2007/11/16/business/16mannkind.html?ex=1352955600&en=d236cde029038835&ei=5088. 
  14. ↑ Lilly/Alkermes—RIP, AIR Insulin, Close Concerns, Inc. Company Watch, Diabetes Close Up #78, www.diabetescloseup.com.
  15. ↑ "MannKind Corporation Receives Complete Response Letter from the FDA for AFREZZA(R)". MannKind Corporation. January 19, 2011. http://investors.mannkindcorp.com/releasedetail.cfm?ReleaseID=792188. 
  16. ↑ "US Afrezza label". FDA. May 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022472s009lbl.pdf. 
  17. ↑ Carroll, John (August 11, 2014). "Sanofi fills some big shoes in $925M Afrezza pact with MannKind". FierceBiotech. http://www.fiercebiotech.com/partnering/sanofi-fills-some-big-shoes-925m-afrezza-pact-mannkind. 
  18. ↑ 18.0 18.1 Staton, Tracy (February 10, 2016). "Sanofi tried and failed with Afrezza. Why does MannKind still think it can win?". FiercePharma. http://www.fiercepharma.com/pharma/sanofi-tried-and-failed-afrezza-why-does-mannkind-still-think-it-can-win. 
  19. ↑ 19.0 19.1 Palmer, Eric (November 10, 2016). "Sanofi forgives MannKind's boatload of debt over failed Afrezza deal". FiercePharma. http://www.fiercepharma.com/pharma/sanofi-forgives-mannkind-boatload-debt-over-failed-afrezza-deal. 
  20. ↑ Snell-Bergeon, Janet K.; Akturk, Halis K.; Rewers, Amanda; Bode, Bruce W.; Klaff, Leslie J.; Peters, Anne; Bailey, Timothy S.; Garg, Satish K. (2018-07-01). "Improved Time-in-Range (TIR) on Continuous Glucose Monitor (CGM) with Technosphere Inhaled Insulin (TI) Compared with Insulin Aspart in T1D Patients—STAT Study" (in en). Diabetes 67 (Supplement 1): 1017–P. doi:10.2337/db18-1017-P. ISSN 0012-1797. http://diabetes.diabetesjournals.org/content/67/Supplement_1/1017-P. 




Retrieved from "https://handwiki.org/wiki/index.php?title=Medicine:Inhalable_insulin&oldid=3270295"