Type 1 & Type 2 Diabetes Studies

Type 1 Patients

Efficacy: Noninferior to Insulin Aspart1

Study Design1: This open-label noninferiority trial compared the change in HbA1C from baseline to 24 week prandial AFREZZA (n=174) with that of subcutaneous insulin aspart (n=170), both with basal insulin, in adult patients (> 18 years old) with type 1 diabetes and HbA1C of 7.5% to 10.0%; the prespecified noninferiority margin was defined as an upper bound of the 95% confidence interval <0.4% in the difference between AFREZZA and insulin aspart groups.

 

Study Results: At week 24, patients treated with inhaled AFREZZA + basal insulin (n=174) had an 0.21% A1C reduction vs 0.40% in those treated with insulin aspart + basal insulin (n=170).

  • Difference between the 2 groups was 0.19% (95% CI: 0.02, 0.36). “Noninferior” was predetermined as the upper limit of the confidence interval to be less than 0.4%.

Inhaled AFREZZA provided less A1C reduction than insulin aspart, and the difference was statistically significant. More subjects in the insulin aspart group achieved the A1C target of <7%.

 

Reference: 1. AFREZZA Prescribing Information.

Type 2 Patients

Effectively Lowered A1C Levels1

Study Design: AFREZZA efficacy was studied in a 24-week, double-blind, placebo-controlled trial of adults with type 2 diabetes (n=353) uncontrolled (A1C>7%) on optimal/maximally tolerated doses of either metformin alone or 2 or more OADs. Patients were treated with AFREZZA + OADs or inhaled placebo powder without insulin + OADs.

 

Study Results: At week 24, 32.3% of patients treated with AFREZZA + oral antidiabetic drugs (OADs) achieved an A1C of <7% vs 15.3% of patients on inhaled placebo + OADs.

 

Reference: 1. AFREZZA Prescribing Information.

Type 1 Patients

Safety: Common adverse reactions (excluding hypoglycemia) from pooled safety results in type 1 diabetes patients 1

Common adverse reactions, excluding hypoglycemia, associated with the use of AFREZZA in the pool of active-controlled trials in type 1 diabetes patients. These adverse reactions were not present at baseline, occurred more commonly on AFREZZA than on comparator, and occurred in at least 2% of patients treated with AFREZZA

Note: Hypoglycemia is the most common adverse reaction associated with insulins, including AFREZZA.

Approximately 27% of patients treated with AFREZZA reported cough, compared to approximately 5.2% of patients treated with comparator. In clinical trials, cough was the most common reason for discontinuation of AFREZZA therapy (2.8% of AFREZZA-treated patients).

 

 

References: 1. AFREZZA Prescribing Information

Type 2 Patients

Safety: Common adverse reactions (excluding hypoglycemia) from pooled safety results in type 2 diabetes patients1

Common adverse reactions, excluding hypoglycemia, associated with the use of AFREZZA in the pool of controlled trials in type 2 diabetes patients. These adverse reactions were not present at baseline, occurred more commonly on AFREZZA than on placebo and/or comparator and occurred in at least 2% of patients treated with AFREZZA.

Note: Approximately 27% of patients treated with AFREZZA reported cough, compared to approximately 5.2% of patients treated with comparator. In clinical trials, cough was the most common reason for discontinuation of AFREZZA therapy (2.8% of AFREZZA-treated patients).

 

References: 1. AFREZZA Prescribing Information

Incidence of Cough

Approximately 27% of patients treated with AFREZZA reported cough, compared to approximately 5.2% of patients treated with comparator. In clinical trials, cough was the most common reason for discontinuation of AFREZZA therapy (2.8% of AFREZZA-treated patients)

 

The incidence of cough was highest during the first 4 weeks of the treatment period. It was predominantly dry and intermittent, and usually occurred within the first 10 minutes of inhalation.

 

Cough (Pooled Safety Population)1

Reference: 1. Data on file, MannKind Corporation

Pulmonary Function Decline

In clinical trials lasting up to 2 years, patients treated with AFREZZA had a 40 mL (95% CI: -80, -1) greater decline from baseline in FEV1 compared to patients treated with other antidiabetes treatments.

 

Mean (+/-SE) Change in FEV1 (L) from Baseline for Patients with Type 1 and Type 2 Diabetes2

 

 

Reference: 2. AFREZZA Prescribing Information

WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE. Acute bronchospasm has been observed in patients with asthma and COPD using AFREZZA. 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.

Indications and Usage

AFREZZA® (insulin human) inhalation powder is a rapid acting inhaled insulin indicated to improve glycemic control in adult patients with diabetes mellitus.

Limitations of Use

  • AFREZZA is not a substitute for long-acting insulin. AFREZZA must be used in combination with long-acting insulin in patients with type 1 diabetes mellitus.
  • AFREZZA is not recommended for the treatment of diabetic ketoacidosis.
  • The safety and efficacy of AFREZZA in patients who smoke has not been established. The use of AFREZZA is not recommended in patients who smoke or who have recently stopped smoking (less than 6 months).

Important Safety Information

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

  • Acute bronchospasm has been observed in patients with asthma and COPD using AFREZZA.
  • 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.

Access the AFREZZA Risk Evaluation and Mitigation Strategy (REMS) program at www.afrezzarems.com.

Contraindications

AFREZZA is contraindicated in patients:

  • During episodes of hypoglycemia.
  • With chronic lung disease (such as asthma or chronic obstructive pulmonary disease [(COPD)] because of the risk of acute bronchospasm.
  • With hypersensitivity to regular human insulin or any of the AFREZZA excipients.

Warnings and Precautions

Acute Bronchospasm: Prior to initiating therapy, evaluate patients with a medical history, physical examination and spirometry (FEV1) to identify potential underlying lung disease. Acute bronchospasm has been observed following AFREZZA dosing in patients with asthma and patients with COPD. The long-term safety and efficacy of AFREZZA in patients with chronic lung disease has not been established.

Change in Insulin Regimen: Monitor blood glucose in all patients treated with insulin. Modify insulin regimen and dose cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral antidiabetic treatment.

Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin therapy, including AFREZZA, and may be serious and life-threatening. Educate patients and caregivers on mitigating the risks associated with hypoglycemia.

Decline in Pulmonary Function: AFREZZA has been shown to cause a decrease in lung function as measured by FEV1. In clinical trials 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 initial 6 months of therapy and annually thereafter even in the absence of pulmonary symptoms. 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 reported in patients exposed to AFREZZA while no cases were reported for the comparators. Two additional cases of lung cancer (squamous cell) 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 outweigh the risks.

Diabetic Ketoacidosis (DKA): Increase the frequency of glucose monitoring and consider an alternate route of administration of insulin in patients at risk for DKA.

Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue AFREZZA, monitor and treat if indicated.

Hypokalemia: 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 occurs, consider dose reduction or discontinuation of TZD.

Drug Interactions

Certain drugs may affect glucose metabolism, increasing the risk of hypoglycemia or decreasing 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.

Adverse Reactions

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