AFREZZA®—ULTRA RAPID-ACTING INHALED INSULIN

Afrezza® is a one-of-a-kind insulin purposefully engineered for ultra-rapid delivery of human insulin1,2

Monomeric insulin diffuses into the systemic circulation more rapidly than their larger counterparts (e.g., dimers, hexamers)3

TIME TO APPEARANCE IN CIRCULATION OF VARIOUS INSULINS1,3-8

  • Afrezza is the only FDA-approved dry-powder formulation of monomeric human insulin for oral inhalation and pulmonary delivery1
  • The clinical significance of the differences in pharmacodynamic (PD) parameters has not been established
filling your afrezza® prescription

See the Afrezza formulation and delivery in action

Afrezza is an ultra rapid-acting inhaled insulin that uses a unique formulation to deliver insulin into the bloodstream via the lungs in <1 minute4

FAST IN, FAST EFFECT, FAST OUT

Afrezza closely mimics physiologic insulin2,10,11

  • Afrezza achieves blood insulin concentrations within 12 minutes and produces maximal glucose lowering in about 45 minutes with a short duration of action (about 3 hours)1,9*
  • Allows for early suppression of endogenous glucose production4,9

MEASURABLE EFFECTS OF ENDOGENOUS AND EXOGENOUS INSULIN1, 12-15*

Insulin Parameters

Time to measurable effect

Time to peak effect

Time for effect to return to baseline

Circulating insulin in Healthy Inndividuals in 12

~ 10 minutes

~ 45 minutes

~ 210 minutes

Pulmonary Delivery 1*

~ 12 minutes

~ 45 minutes

~ 180 minutes

Sc Delivery
3,11,12

~ 17-30 minutes

~ 90-120 minutes

~ 275-320 minutes

Physiologic Insulin

*Data shown are for the 12-unit doses. The 48-unit doses of Afrezza have a time to peak effect of 55 minutes and time for effect to return to baseline of 270 minutes.1

Insulin secretion data from a study in healthy subjects (n=10) to estimate insulin sensitivity based on an oral glucose tolerance test or a meal glucose tolerance test (MGTT).12
Delivery data obtained from the prescribing information for inhaled and SC insulin therapies1,13,14 and a quantitative comparison of glucose infusion rate (GIR) profiles for Afrezza and lispro.15 Comparisons of efficacy and safety should not be made in the absence of head-to-head studies.

Afrezza approximates the time-action profile of endogenous insulin1,2,10,11

AVERAGE INSULIN CONCENTRATION
DURING MGTT IN HEALTHY ADULTS12

Average Insulin Concentration

Data from a study in healthy subjects (n=10) that estimated insulin sensitivity during a MGTT.12

TIME-ACTION PROFILES OF AFREZZA
AND SC RAI COMPARATOR3

Time Action Profiles

Data from a randomized, controlled, 6-treatment crossover, dose-response study that compared Afrezza with the SC RAI lispro, in 30 patients with T1D. On average the pharmacodynamic (PD) effect of Afrezza, measured as area under the glucose infusion rate time curve (AUC GIR), increased linearly with doses up to 48 units.3 The time course of insulin action may vary considerably in different individuals or within the same individual.

*The clinical significance of the differences in PD parameters has not been established.

MEALTIME SPONTANEITY

The onset and offset of Afrezza closely mimics
physiologic insulin1,2,10,11

  • Ultra-rapid onset
  • Short time to peak effect
  • Time to return to baseline similar to
    physiologic insulin

Actual Afrezza User

References: 1. Afrezza (insulin human) Inhalation Powder Prescribing Information. MannKind Corporation 2. Heinemann L, Baughman R, Boss A, Hompesch M. Pharmacokinetic and pharmacodynamic properties of a novel inhaled insulin. J Diabetes Sci Technol. 2017;11(1):148-156. 3. Holleman F, Hoekstra JB. Insulin lispro. N Engl J Med. 1997;337(3):176-183. 4. Data on file. MannKind Corporation. 5. Heise T, Hövelmann U, Brøndsted L, Adrian CL, Nosek L, Haahr H. Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart. Diabetes Obes Metab. 2015;17(7):682-688. 6. Heise T, Stender-Petersen K, Hövelmann U, Bonde Jacobsen J, Nosek L, Zijlstra E, et al. Pharmacokinetic and pharmacodynamic properties of faster-acting insulin aspart versus insulin aspart across a clinically relevant dose range in subjects with type 1 diabetes mellitus. Clin Pharmacokinet. 2017;56(6):649-660. 7. Heise T, Pieber TR, Danne T, Erichsen L, Haahr H. A pooled analysis of clinical pharmacology trials investigating the pharmacokinetic and pharmacodynamic characteristics of fast-acting insulin aspart in adults with type 1 diabetes. Clin Pharmacokinet. 2017;56(5):551-559. 8. Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, Di Vincenzo A, et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000;49(12):2142-2148. 9. Rosenstock J, Lorber DL, Gnudi L, et al. Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial. Lancet. 2010;375(9733):2244-2253. 10. Rave K, Heise T, Heinemann L, Boss AH. Inhaled Technosphere insulin in comparison to subcutaneous regular human insulin: time action profile and variability in subjects with type 2 diabetes. J Diabetes Sci Technol. 2008;2(2):205-212. 11. Boss AH, Petrucci R, Lorber D. Coverage of prandial insulin requirements by means of an ultra-rapid-acting inhaled insulin. J Diabetes Sci Technol. 2012;6(4):773-779. 12. Caumo A, Bergman RN, Cobelli C. Insulin sensitivity from meal tolerance tests in normal subjects: a minimal model index. J Clin Endocrinol Metab. 2000;85(11):4396-4402. 13. Fiasp (insulin aspart injection) Prescribing Information. Novo Nordisk. 14. Lyumjev (insulin lispro-aabc injection) Prescribing Information. Eli Lilly and Company. 15. Grant M, Heise T, Baughman R. Comparison of Pharmacokinetics and Pharmacodynamics of Inhaled Technosphere Insulin and Subcutaneous Insulin Lispro in the Treatment of Type 1 Diabetes Mellitus. Clin Pharmacokinet. 2022;61(3):413-422.

US-AFR-2153

Important Safety Information  for AFREZZA® (insulin human) Inhalation Powder

WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE. Acute bronchospasms has been observed in AFREZZA-treated patients with asthma and COPD. AFREZZA is contraindicated in patients with chronic lung disease such as asthma or COPD. Before initiating AFREZZA, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.

Important Safety Information
Hide Important Safety Information

Indications and Usage:
Afrezza®(insulin human) Inhalation Powder is a rapid acting inhaled human insulin indicated to improve glycemic control in adult patients with diabetes mellitus.

Limitations of Use: Not recommended for the treatment of diabetic ketoacidosis, not recommended in patients who smoke or have recently stopped smoking.

Important Safety Information

WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE

  • Acute bronchospasms has been observed in AFREZZA-treated patients with asthma and COPD
  • AFREZZA is contraindicated in patients with chronic lung disease such as asthma or COPD.
  • Before initiating AFREZZA, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.

 

Contraindications
AFREZZA is contraindicated: during episodes of hypoglycemia, in patients with chronic lung disease (such as asthma or chronic obstructive pulmonary disease [COPD]) because of the risk of acute bronchospasm, and in patients with hypersensitivity to regular human insulin or any of the excipients in AFREZZA.

Warnings and Precautions
Acute Bronchospasm: In a study of patients with asthma whose bronchodilators were temporarily withheld for assessment, bronchoconstriction and wheezing following AFREZZA dosing was reported. Before initiating therapy, evaluate all patients with a medical history, physical examination, and spirometry (FEV1) to identify potential underlying lung disease. Do not use in patients with chronic lung disease such as asthma or COPD.

Hypoglycemia or Hyperglycemia with Changes in Insulin Regimen: Glucose monitoring is essential for patients receiving insulin therapy. Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made under close medical supervision and the frequency of blood glucose monitoring should be increased. For patients with type 2 diabetes, dosage modifications of concomitant oral antidiabetic treatment may need to be needed.

Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulins, including AFREZZA. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly, and symptoms may differ across patients and change over time in the same patient. Patients and caregivers should be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia.

Decline in Pulmonary Function: AFREZZA causes a decline in lung pulmonary function over time as measured by FEV1. In clinical trials excluding patients with chronic lung disease and lasting up to 2 years, AFREZZA-treated patients experienced a small (40 mL) but greater FEV1 decline than comparator-treated patients. Assess pulmonary function with spirometry at baseline, after the first 6 months of therapy and annually thereafter even in the absence of pulmonary symptoms. In patients who have a decline of ≥20% in FEV1 from baseline, consider discontinuing AFREZZA. Consider more frequent lung function assessment in patients with pulmonary symptoms, e.g., wheezing, bronchospasm, breathing difficulties, or persistent or recurring cough. If symptoms persist, discontinue AFREZZA.

Lung Cancer: In clinical trials, 2 cases of lung cancer were observed in patients exposed to AFREZZA while no cases were reported for the comparators. In both cases, a prior history of heavy tobacco use was identified as a risk factor for lung cancer. Two additional cases of lung cancer (squamous cell and lung blastoma) were reported in non-smokers exposed to AFREZZA after the trial completion. These data are insufficient to determine whether AFREZZA has an effect on lung or respiratory tract tumors. In patients with active lung cancer, a prior history of lung cancer, or in patients at risk of lung cancer, consider whether the benefits of AFREZZA use outweigh this potential risk.

Diabetic Ketoacidosis (DKA): In clinical trials enrolling patients with type 1 diabetes, diabetic ketoacidosis (DKA) was more common in AFREZZA-treated patients (0.43%; n=13) than in comparator-treated patients (0.14%; n=3). Patients with type 1 diabetes should always use AFREZZA in combination with basal insulin. In patients at risk for DKA, such as those with an acute illness or infection, increase the frequency of glucose monitoring and consider discontinuing AFREZZA and giving insulin using an alternate route of administration.

Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including AFREZZA . If hypersensitivity reactions occur, discontinue AFREZZA, treat per standard of care and monitor until symptoms and signs resolve.

Hypokalemia: All insulin products, including AFREZZA, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Closely monitor potassium levels in patients at risk of hypokalemia and treat if indicated.

Fluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs): Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of TZDs and insulin. Observe these patients for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the TZD should be considered.

Drug Interactions
Certain drugs may affect glucose metabolism, increasing the risk of hypoglycemia or deceasing or increasing the blood glucose lowering effect of AFREZZA. Dose adjustment and increased frequency of blood glucose monitoring may be required. Co-administration of beta-blockers, clonidine, guanethidine, and reserpine with AFREZZA may reduce the signs and symptoms of hypoglycemia. For full list, see Prescribing Information.

Adverse Reactions
The most common adverse reactions associated with AFREZZA are hypoglycemia, cough, and throat pain or irritation.

To report SUSPECTED ADVERSE REACTIONS, contact MannKind Corporation at 1-877-323-8505 or FDA at www.fda.gov/medwatch or call 1-800-FDA-1088 (1-800-332-1088).

Please see full Prescribing Information, including BOXED WARNING for AFREZZA.

AFREZZA and the Afrezza logo, MANNKIND, BLUHALE, TECHNOSPHERE and AFREZZAASSIST are registered trademarks, READY. SET. INHALE., the Racing Car design and BLUHALE PRO are marks, all owned by MannKind Corporation. © MannKind Corporation 2023. This site is intended for use by US healthcare professionals only

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