Medical Writing for Pharmaceutical Company

Afrezza®

Afrezza®is rapidly acting inhaled insulin built on the Techtechnology and noosphere platform technology and it is a prescription drug made from a dry powder form of human insulin. The drug was approved by the FDA in July 2014 as an inhalation powder to improve glycemic control for type I diabetes mellitus (TIDM) or type II diabetes Mellitus (T2DM) (FDA n.d.). The drug is manufactured by MannKind Corp. /Sanofi-AventisUS and it employs the new Gen2 inhaler. Afrezza is a drug-device that includes a combination of a dry powder formulation of recombinant insulin that is packed in pre-metered unit dose cartridges and an inhaler device. The Afrezza dose is individualized and is administered through oral inhalation before each meal. Initially, Afrezza® was developed as mealtime insulin since they cover the blood glucose changes after absorption of macronutrients (FDA Ref ID: 3533681).

Formulation

Afrezzaconsists of single-use plastic cartridges that are filled with a white powder containing human insulin that is administered via oral inhalation using an AfrezzaInhaler only. The human insulin is produced by recombinant DNA technology that utilizes a non-pathogenic laboratory strain of Escherichia coli (K12), a powder suitable for inhalation produced through a freeze-drying process (Goldberget al., 2015). The human insulin has an empirical formula C257H383N65O77S6in addition, it has a molecular weight of 5808. The dry powder for the formulation of Afrezza® inhalation is supplied as 4-unit, 8-unit, or 12-unit cartridges. In this case, the 4-unit cartridge contains 0.35mg of insulin, the 8-unit cartridge has 0.7mg of insulin, while the 12-unit cartridge contains 1mgof insulin. The inhaler is breath-powered by the patient, the powder aerosolizes when the patient inhales through the device, and as a result, the drug is delivered to the lungs, however, the amount delivered depends on on individual patient factors (Afrezza n.d.).

Why was Afrezza® formulated?

Diabetes is a common public health problem in the world. It is accompanied by multiple comorbidities and health complications. Diabetes is a major cause of death and various chronic diseases such as heart disease and stroke. Its management is complex and requires multiple risk-reduction strategies to prevent or reduce complications. The US Food and Drug Administration (FDA) approved Afrezza®insulin human inhalation powder to improve glycemic control in adults with diabetes (Fala et al., 2015). It controls high blood sugar in adults with type 1 diabetes mellitus and type 2 diabetes mellitus.

Mechanism of Action

Afrezza®is a rapidly acting inhaled insulin. Insulin lowers blood glucose levels by stimulating peripheral glucose uptake via skeletal muscles and fat. It also inhibits hepatic glucose production. After inhalation of the powdered insulin, it enters the systemic circulation after pulmonary absorption, its metabolism and is achieved elimination are similar to regular human insulin. Its peak level isachieved within 12 to 15 minutes after inhalation and the serum insulin concentrations decline to near baseline levels by approximately 180 minutes. The human inhalation powder is administered before meals using a single inhalation per cartridge. The dosing is individualized and before its administration, a detailed medical history, physical examination, and spirometry. It should be conducted to rule out the possibility of any lung disease(Fala et al., 2015)

 

Limitations for Afrezza® Use

Itis not advisable to use Afrezza® as a substitute for long-acting insulin, however, it should be used in combination with long-acting insulin, especially in patients with type 1 diabetes. Furthermore, Afrezza® should not be used for treating diabetic ketoacidosis and it is not recommended in patients who are smoking or patients who stopped smoking recently. Patients with chronic lung diseases such as asthma and COPD should not use Afrezza® due to the risk of developing acute bronchospasm. In addition, patients with low blood sugar reactions should not use the drug as well as patients with allergic reactions to any of its ingredients.

Adverse Reactions

The most common side effect of Afrezza® is low blood sugar which can be life-threatening and symptoms include shaking, sweating, rapid heartbeat, and blurred vision which may cause heart or brain damage (Afrezza, 2014). Other adverse reactions include lung cancer, hypersensitivity reactions, a decline in pulmonary function, acute bronchospasm in patients with chronic lung disease, and diabetic ketoacidosis.

Superiority

Afrezza®was the second rapid inhaled insulin to be approved by the FDA in 2014 on themarket. Exubera was the first drug to be approved in 2006, however, Pfizer withdrew Exubera from the market in January 2016 due to poor sales. Pfizer had bought the worldwide rights to Exubera from Sanofi Aventis and the product was introduced to the market in Britain in 2006. Sanofi had a marketing agreement for Afrezza®with MannKind but withdrew from the $ 925 million deal also due to poor sales(Oleck et al., 2016). The worldwide sales of Exubera in the first nine months of 2007 was $12m yet they had projected a $2bn sale. It is believed that restrictive guidelines, for example, the use of Exubera only in restricted cases, may have resulted in poor sales (Bailey et al., 2007). Currently, Afrezza® is the only inhaled insulin available in the U.S. (Marckx et al.,2019)

The marketing of Afrezza® has been difficult due to poor insurance coverage, new adverse effects, and competition from other therapeutic alternatives. To address the challenge, Afrezza® should be priced competitively to gain favorable payer coverage and make strategies for short-term cash flow, and to address the possible negative effects (Oleck et al., 2016

Competing Formulations

There are various therapeutic options available in the market for patients with type 1 or type 2 diabetes and there are also new development arising constantly. Afrezza®is usually used in combination with another anti-glycemic. The prevalence and incidence of diabetes continue to escalate therefore the need to have a safe, efficacious, easy, and affordable solution to the problem. Thus a continuous advancement in diabetes management in the future is necessary and Afrezza® has got a chance to succeed even with emerging therapies and medical devices (Olecket al., 2016).

Afrezza (Insulin human inhalation powder): Uses, dosage, side effects, interactions, warning. (n.d.). RxList. https://www.rxlist.com/afrezza-drug.htm#description

Afrezza. (2014, November).https://file:///C:/Users/user/AppData/Local/Temp/Afrezza%20Fact%20Sheet%2012.12.14.pdf

Bailey, C. J.,& Barnett, A. H. (2007). Why is Exubera being withdrawn? BMJ,335(7630), 1156-1156. https://doi.org/10.1136/bmj.39409.507662.94

Fala L. (2015).Afrezza (Insulin Human) Inhalation Powder Approved for the Treatment ofPatients with Type 1 or Type 2 Diabetes. American health & drug benefits,8(Spec Feature), 40–43.

FDA Ref ID: 3533681. (n.d.). CENTER FOR DRUG EVALUATION AND RESEARCH: SUMMARY REVIEW. Accessdata.https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/022472Orig1s000SumR.pdf

FDA Ref ID:3533688.https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022472lbl.pdf

Goldberg,T., & Wong, E. (2015). Afrezza (Insulin Human) Inhalation Powder: A NewInhaled Insulin for the Management of Type-1 or Type-2 Diabetes Mellitus. P& T: a peer-reviewed journal for formulary management, 40(11),735–741.

Marckx, B., & Dushyanth, A. (2013, May 13). ZacksSmall-Cap Research.https://s1.q4cdn.com/460208960/files/News/2019/Zacks_SCR_Research_05132019_MNKD_Marckx.pdf

Oleck,J., Kassam, S., & Goldman, J. D. (2016). Commentary: Why Was InhaledInsulin a Failure in the Market? Diabetes spectrum: a publication of theAmerican Diabetes Association, 29(3), 180–184.https://doi.org/10.2337/diaspect.29.3.180