Afrezza HCP » Efficacy

Discover METRICS that MATTER

T1D TRIAL

AFFINITY-1

AFREZZA effectively lowers A1C^1,2

In the AFFINITY-1 pivotal T1D trial, patients treated with AFREZZA and patients treated with SC RAI achieved similar average A1C reductions from baseline. Baseline A1C levels were 7.94% for patients treated with AFREZZA and 7.92% for patients using SC RAI. By Week 24, AFREZZA reduced A1C to 7.73% (-0.21%), and SC RAI to 7.52% (-0.40%), resulting in a between-group difference of 0.19%

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 less A1C reduction than RAI, satisfied the non-inferiority margin of 0.4%, and the difference was statistically significant. More subjects in the SC RAI group achieved the A1C target of ≤7%.¹

T2D TRIAL

AFFINITY-2

AFREZZA significantly decreased A1C levels in inadequately controlled patients on oral agents^2,3*

In the AFFINITY-2 pivotal T2D trial, treatment with AFREZZA plus OADs provided a mean reduction in A1C that was statistically significantly greater compared with the A1C reduction observed in the placebo plus OADs group. Baseline A1C levels were 8.25% for patients treated with AFREZZA plus OADs and 8.27% for patients using placebo plus OADs. By Week 24, AFREZZA reduced A1C by 0.82% compared with 0.42% in the placebo group, resulting in a between-group difference of 0.4% (P<0.0001). Additionally, 32% of AFREZZA-treated subjects achieved an A1C of ≤7%, compared with 15% in the placebo group

Data from a 24-week, randomized, double-blind, placebo-controlled study in insulin-naïve patients with T2D whose disease was inadequately controlled with optimal/maximal-tolerated doses of OADs. After a 6-week run-in period, patients were randomized to receive either AFREZZA plus OADs (n=177) or inhaled (placebo) powder without insulin plus OADs (n=176).³

*Inadequately controlled patients included those whose A1C was ≥7.5% to ≤10%.

The ADA recommends patients with diabetes spend ≥70% Time in Range (TIR) per day⁴

AFREZZA^® ambulatory glucose profile case example⁵

Improved TIR correlates with A1C⁴

CGM data from a single AFREZZA patient.⁵

Levin Study

AFREZZA added to existing treatments significantly improved Time in Range⁶

Change in TIR Over 12 Weeks⁶

Bar chart showing how AFREZZA resulted in a 56% relative increase in Time in Range over 12 weeks.

Mean daily BG levels decreased by 41 mg/dL (P<0.0002), a 20% relative decrease⁴

Data from an open-label, non-randomized, clinical research study of 20 adult patients (≥18 years old) with T2D and inadequately controlled (A1C 7.5% to 11.5%) after at least 6 months of other diabetes treatments, including OAs and basal insulin. AFREZZA treatment was added to each patient’s current therapy, administered before each meal, and titrated per protocol. A1C and blinded CGM measurements were recorded at baseline and end of study, patients continued to self-monitor blood glucoses daily. CGM data were incomplete for 1 patient.⁶

STAT Study

AFREZZA increased Time in Range⁷

TIR With AFREZZA Versus SC RAI⁷

Patients† gained ~2 hours in TIR each day⁷

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 CGM throughout the trial.⁷

^†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.⁷

AFREZZA continues to exhibit a weight-neutral profile^3,5,7,9-12

Note: Cross-trial comparison should not be made due to differences in patient populations and trial designs.

^§Values represent the sample size at the end of the respective studies

^¶Patients in the Usual Care group were on AID or MDI.

In the most recent study, INHALE-3 AFREZZA vs Usual Care, the comparator had a mean weight gain of 1.4 kg vs AFREZZA, which had 0.1 kg from baseline to 17 weeks¹⁰

A1C=glycated hemoglobin; AID=automated insulin delivery; BG=blood glucose; CGM=continuous glucose monitor; IQR=interquartile range; MDI=multiple daily injections; OAs=oral antidiabetic agents; PPG=postprandial glucose; PPGE=postprandial glucose excursions; SC RAI=subcutaneous rapid-acting insulin; T1D=type 1 diabetes; T2D=type 2 diabetes; TIR=time in range.

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. Afrezza (insulin human) Inhalation Powder Prescribing Information. MannKind Corporation. 3. Rosenstock J, Franco D, Korpachev V, et al. Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents. Diabetes Care. 2015;38(12):2274-2281. 4. American Diabetes Association Professional Practice Committee. 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes—2024. Diabetes Care. 2924;47(Supplement_1):S111-S125. 5. Data on file. MannKind Corporation. 6. Levin P, Hoogwerf BJ, Snell-Bergeon J, Vigers T, Pyle L, Bromberger L. Ultra rapid-acting inhaled insulin improves glucose control in patients with type 2 diabetes mellitus. Endocr Pract. 2021;27(5):449-454. 7. 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. 8. 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. 9. McGill JB, Peters A, Buse JB, et al. Comprehensive pulmonary safety review of inhaled Technosphere^® insulin in patients with diabetes mellitus. Clin Drug Investig. 2020;40(10):973-983. 10. INHALE-3 Clinical Study Report, 2024. MannKind Corporation. 11. Hoogwerf BJ, Pantalone KM, Basina M, et al. Results of a 24-week trial of technosphere insulin versus insulin aspart in type 2 diabetes. Endocr Pract. 2021;27(1):38-43. 12. 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.

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 bronchospasm 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 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 decreasing 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.