T1D: PROVEN CONTROL

Proven A1C control comparable to SC RAI1

  • Afrezza met the non-inferiority margin: Specifically, the between-group difference in A1C levels from baseline to study end was 0.19% (95% CI, 0.02-0.36), satisfying the non-inferiority margin of 0.4%1

MEAN A1C LEVELS OVER 24-WEEK TREATMENT PERIOD1

Data from an open-label, non-inferiority trial comparing the change in A1C from baseline to week 24 of prandial Afrezza (n=174) with that of SC RAI (n=170), both with basal insulin, in adult patients (≥18 years) with T1D and an A1C of 7.5% to 10%. Afrezza provided less A1C reduction than RAI, satisfied the non-inferiority margin of 0.4%, and the difference was statistically significant. More subjects in the SC rapid-acting group achieved the A1C target of ≤7%.1

In an open-label, non-inferiority trial, Afrezza lowered A1C comparable to SC RAI1

  • Trial compared the change in A1C from baseline to week 24 of prandial Afrezza (n=174) with that of SC RAI (n=170), both with basal insulin, in adult patients (≥18 years) with T1D and A1C of 7.5% to 10%1
  • Afrezza provided less A1C reduction than RAI, and the difference was statistically significant. More subjects in the SC rapid-acting group achieved the A1C target of ≤7%1

Proven mealtime control2

POSTPRANDIAL GLUCOSE (PPG) LEVELS ASSOCIATED WITH AFREZZA2

Data from the STAT study of patients with T1D with A1C levels 6.5% to 10%. Individuals were randomized to treatment with titrated Afrezza (n=22) or titrated SC RAI aspart (n=34) and included in the final analysis. All were required to wear a real-time continuous glucose monitor (CGM) throughout the trial.2

  • The STAT trial assessed both postprandial glucose excursions (PPGE) in 1-4 hours and time-in-range (TIR: 70-180 mg/dL) using a real-time CGM with Afrezza versus insulin aspart in patients with T1D on multiple daily injections2
  • Afrezza demonstrated lower PPG values at 60 and 90 minutes post-meal as compared with SC RAI2
  • Significantly lower PPGE post-breakfast and -lunch versus SC RAI2

Improvement of TIR2

TIR WITH AFREZZA VERSUS SC RAI2

Data from the STAT study of patients with T1D with A1C levels 6.5% to 10%. Individuals were randomized to treatment with titrated Afrezza (n=22) or titrated SC RAI aspart (n=34) and included in the final analysis. Patients were defined as compliant if ≥90% of postmeal Afrezza dosages were taken per protocol, with at least one of the postmeal inhalations taken if indicated per meal. All were required to wear a real-time continuous glucose monitor (CGM) throughout the trial.2

  • Compared with the SC RAI group, TIR was significantly greater in the Afrezza-compliant group (62.5% ± 2.6% versus 53.8% ± 1.7%, P=0.009), and time in hyperglycemia (>180 mg/dL) was lower (34.2% ± 2.7% versus 41.0% ± 1.7%, P=0.045)2
  • Additionally, those treated with Afrezza versus aspart spent less time in hypoglycemia (<60 and <50 mg/dL, both P<0.05)2

Lower rates of postprandial hypoglycemia3

HYPOGLYCEMIA EVENT RATE WITH AFREZZA3

Data from a post-hoc regression analysis on a subset of the AFFINITY-1 study of adults (n=279) with T1D ≥12 months and an A1C level of 7.5% to 10%. Patients were randomized to receive basal insulin plus either Afrezza or SC RAI aspart.3 These results should be interpreted along with the efficacy results for this study.

  • A primary outcome measure was event rates for levels 1, 2, and 3 hypoglycemia, respectively, defined as blood glucose levels of ≤70.3 mg/dL, <54.1 mg/dL, or requiring assistance of another person to take corrective actions3
  • Patients treated with Afrezza experienced significantly fewer level 1 and 2 hypoglycemic event rates than participants treated with insulin aspart3
  • Hypoglycemia is the most common adverse reaction of insulin therapy, including Afrezza, and may be serious and life-threatening.4 Educate patients and caregivers on recognizing symptoms and mitigating the risks associated with hypoglycemia

Lower rates of late postprandial hypoglycemia1

POST-MEAL HYPOGLYCEMIA EVENT RATES WTH AFREZZA VERSUS SC RAI1

Data from an open-label, non-inferiority trial compared the change in A1C from baseline to week 24 of prandial Afrezza (n=174) with that of SC RAI (n=170), both with basal insulin, in adult patients (≥18 years) with T1D and A1C of 7.5% to 10%. Afrezza provided a mean reduction in A1C that met the pre-specified non-inferiority margin of 0.4%. Afrezza provided less A1C reduction than RAI, and the difference was statistically significant. More subjects in the SC rapid-acting group achieved the A1C target of ≤7%.1

  • Patients who received Afrezza had an overall lower hypoglycemia event rate than those who received aspart (9.8 events/patient-month versus 14.0 events/patient-month, P<0.0001)1
  • Specifically, event rates were higher in the >2-5 hours after meals in the insulin aspart group as compared with the Afrezza group1
  • These results should be interpreted along with the efficacy results for this study

References: 1. Bode BW, McGill JB, Lorber DL, Gross JL, Chang PC, Bregman DB. Inhaled Technosphere insulin compared with injected prandial insulin in type 1 diabetes: a randomized 24-week trial. Diabetes Care. 2015;38(12):2266-2273. 2. Akturk HK, Snell-Bergeon JK, Rewers A, et al. Improved postprandial glucose with inhaled Technosphere insulin compared with insulin aspart in patients with type 1 diabetes on multiple daily injections: the STAT study. Diabetes Technol Ther. 2018;20(10):639-647. 3. Seaquist ER, Blonde L, McGill JB, et al. Hypoglycaemia is reduced with use of inhaled Technosphere® Insulin relative to insulin aspart in type 1 diabetes mellitus. Diabet Med. 2020;37(5):752-759. 4. Afrezza (insulin human) Inhalation Powder Prescribing Information. MannKind Corporation.

US-AFR-2131

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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