By: Elissa Tam, PharmD Candidate c/o 2015
Patients with Type 1 or Type 2 diabetes who cannot control their glucose levels simply by taking oral medications have to inject insulin daily. They also have to measure their glucose levels by using strips and lancets on a regular basis. For patients, especially elderly ones, the process can be bothersome and frustrating and so pharmaceutical companies are trying to find innovative ways to make insulin delivery more convenient.
As of June 29, 2014, the FDA has approved an inhaled form of insulin called Afrezza® (insulin human), designed by the drug company MannKind.1 MannKind has been experimenting with an insulin-inhalation system that would reduce the need for injecting insulin since the company submitted a new drug application for Afrezza® back in 2010. In early 2011, the FDA rejected the drug and demanded two additional clinical trials. After completing the trials, MannKind resubmitted Afrezza® in October 2013. Early in April 2014, the U.S. Food and Drug Administration advisory panel voted in favor of MannKind’s Afrezza®. However, health regulators delayed a decision on the experimental diabetes inhalant for three months so that the FDA could review the data submitted by MannKind more carefully.1 Finally, in late June, MannKind obtained regulatory clearance for its device.
Afrezza® is advertised as a first-in-class, ultra rapid-acting mealtime insulin therapy that comes as a drug-device combination product—inhalation powder single use dose cartridges and the small Afrezza® inhaler.1 Earlier, there was an inhaled device called Exubera, marketed by Pfizer, that was discussed as a possible alternative to injectable insulin. However, concerns regarding a serious risk of dosing errors with Exubera (insulin is traditionally administered in international units but Exubera will be prescribed in milligrams), failure to be accepted by patients and physicians, and the development of lung cancer have Pfizer discontinuing the production of Exubera, making Afrezza® the first inhalation device for diabetes to be approved.2
Administered at the start of a meal, Afrezza® dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Similar to the rapid-acting insulin products that are available in the market now (e.g. insulin aspart (Novolog®) and insulin lispro (Humalog®), it should be administered 15 minutes before mealtime.2 In Type 1 diabetics, Afrezza® would be used with injected basal insulin.3 The FDA advisory panelists cited the advantages of more rapid onset and shorter duration of insulin action, resulting in a lower risk of hypoglycemia, in addition to greater acceptance of inhaled-insulin therapy for patients with Type 2 diabetes who refuse or are unable to self-inject insulin. It is, however, not a substitute for long-acting insulin and must be used in combination with long-acting insulin in patients with Type 1 diabetes.4
In an Afrezza® clinical program, which involved more than 6,500 adult patients, it was demonstrated that the inhaled insulin reduced HbA1c and resulted in less weight gain in comparison to currently available rapid-acting analogs.5 In a pivotal trial involving 353 patients with Type 2 diabetes inadequately controlled on one or more oral agents, Afrezza® was superior to placebo in lowering HbA1c at 24 weeks, with a week-24 treatment difference of -0.40 (P<.0001).1 However, in another study of 344 patients with type 1 diabetes, Afrezza® had significantly inferior HbA1c reduction compared with premeal injections of insulin aspart, although the difference remained within the pre-specified non-inferiority margin.1
In clinical trials of up to two years duration involving Type 1 and Type 2 adult patients with diabetes, any detrimental changes in lung function observed were small, did not progress, and resolved when Afrezza® treatment was discontinued.5 Moreover, the most common respiratory side effect experienced with Afrezza® in trials was a mild, transient, non-productive cough which occurred in 27% of all study subjects and lead to treatment discontinuation in 3%.5 A total of 4 cases of lung cancer occurred in patients who had used Afrezza®, 2 during the trial in smokers and 2 others, both squamous-cell tumors, at 2.6 and 3.8 years after the end of the trial in nonsmokers. Because of the risk of bronchospasm in patients with underlying lung disease, including chronic obstructive pulmonary disease (COPD) and asthma, Afrezza® has a black box warning advising such patients to not be used with this medication.4 Current smokers or those who had smoked in the past are also recommended to not use Afrezza®. 1
MannKind hopes to have the drug on the market in the upcoming months, though just how popular the inhaled device will be remains to be seen. Despite certain questionable risks and effects with the medication, Afreeza® serves as a new option for millions of Americans with diabetes by helping reduce the number of daily injections and by making controlling glucose levels more manageable.
- Tucker ME. “FDA Advisory Panel Endorses Inhaled-Insulin Product Afrezza.” Medscape Medical News. http://www.medscape.com/viewarticle/822957. Published April 02, 2014. Accessed July 20, 2014.
- Neumiller JJ, Campbell RK. “Technosphere Insulin: An Inhaled Prandial Insulin Product.” BioDrugs. 2010 Jun; 24(30: 165-72.
- Boss AH, Petrucci R, Lorber D. “Coverage of Prandial Insulin Requirements by Means of an Ultra-Rapid-Acting Inhaled Insulin.” Journal of Diabetes Science and Technology. Jul 2012; 6(4): 773-779
- FDA approves Afrezza to Treat Diabetes. FDA. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm403122.htm. Published June 27, 2014. Accessed June 30, 2014.
- Afrezza – A First-in-class Ultra Rapid-Acting Insulin. MannKind Corporation. http://www.mannkindcorp.com/product-pipeline-diabetes-afrezza.htm. Published 2010-2014. Accessed July 20, 2014.
[pubmed_related keyword1=”diabetes” keyword2=”insulin” keyword3=”afrezza”]