Afrezza HCP » INHALE-3 Data

INHALE-3 Study Summary

Study Design

Efficacy

Safety

Individualized Insulin Therapy

INHALE-3 Study: Comparing AFREZZA to injectables and pumps

Learn about our latest INHALE-3 clinical trial

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Dr. Kevin Kaiserman

SVP Medical Affairs

INHALE-3 Study Summary

Primary endpoint met: AFREZZA demonstrated similar A1C control compared with Usual Care¹

More patients achieved A1C goal vs MDI¹

30% of participants who switched from MDI to AFREZZA achieved an A1C <7% compared to 4% who remained on MDI

Achieved similar results to AID without a tethered device¹

The AFREZZA and AID groups achieved comparable glycemic goals (A1C <7% and TIR >70%)

Demonstrated established safety profile¹

Similar percentage of hypoglycemia by CGM
No significant difference in FEV₁

Consider AFREZZA in your treatment options

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Study Design

Diabetes knows no boundaries: 19 sites selected across the U.S.

123 randomized participants ≥18 years old with T1D^1,2

Map of the United States indicating the 19 clinical study sites for the INHALE-3 Study.

INHALE-3 patient characteristics^1,2

Two pie charts depicting patient characteristics in the INHALE-3 study: baseline A1C ≥7.0% and Usual Care insulin delivery modalities (AID, MDI, other).

INHALE-3 study design^1,2

Diagram depicting the study design of the INHALE-3 Study, showing the screening phase, randomized trial/treatment phase, and extension phase.

Primary Endpoint Data

At baseline:

Both the AFREZZA group (n=62) and the usual care group (n=61) had a baseline average A1C of 7.6%, indicating similar baseline glycemic control in both groups

After 17 weeks:

The AFREZZA group (n=57) maintained an average A1C of 7.6%
The Usual Care group (n=58) had an average A1C of 7.5%
The non-inferiority margin of 0.4% was met (P=0.01^‡)

^‡17-week treatment difference between AFREZZA and Usual Care (95% CI): 0.11 (-0.10, 0.33)

Patients randomized to AFREZZA maintained A1C levels of 7.6 over 17 weeks²

Efficacy

AFREZZA vs Usual Care: more patients on AFREZZA achieved A1C goals¹

More AFREZZA patients achieved an A1C <7% compared to Usual Care

A1C Change From Baseline in All Participants

(Exploratory endpoint)

Bar chart showing that more AFREZZA patients achieved an A1C <7.0% compared with Usual Care (30% vs 17%, respectively).

ª17-week treatment difference between AFREZZA and Usual Care (95% CI); P-value.

Proportion of patients experiencing a >0.5% change in A1C: Among all subjects, 21% of AFREZZA patients had a >0.5% decrease in A1C compared with 5% in the Usual Care group. Conversely, 26% of AFREZZA patients achieved a >0.5% increase in A1C, compared with 3% in the Usual Care group

In patients with a baseline A1C >7%, only AFREZZA patients achieved A1C goals by Week 17

Bar chart showing that only AFREZZA patients (21%) achieved A1C goals >7.0% by Week 17 compared with 0% on Usual Care.

Proportion of patients experiencing a >0.5% change in A1C: Among subjects with a baseline A1C >7%, 28% of AFREZZA patients had a >0.5% decrease in A1C compared with 7% in the Usual Care group. Conversely, 21% of AFREZZA patients achieved a >0.5% increase in A1C, compared with 2% in the Usual Care group

AFREZZA vs Usual Care: time in range outcomes¹

AFREZZA maintained TIR at Week 17

Bar chart showing that AFREZZA maintained time in range outcomes similar to Usual Care at Week 17.

More AFREZZA patients improved TIR

Time in Range (70-180 mg/dL) >70% at 17 Weeks

Bar chart showing that more AFREZZA patients achieved TIR >70% at 17 weeks compared with those on Usual Care (24% vs 13%, respectively).

^b17-week treatment difference between AFREZZA and Usual Care (95% CI); P-value.

Proportion of patients experiencing a ≥10% change in TIR: Among all subjects, 25% of AFREZZA patients increased TIR by ≥10% compared to 14% on Usual Care. Conversely, 31% of AFREZZA patients decreased TIR by ≥10%, compared to 19% on Usual Care

Delivery methods matter^1§

More AFREZZA patients achieved…

Patients who switched to AFREZZA experienced…

Bar chart showing that patients who switched to AFREZZA achieved A1C and TIR results similar to those who remained on AID (30% vs 33%; 23% vs 27%, respectively).

Weight-neutrality¹

The Usual Care group gained statistically more weight than the AFREZZA group

AFREZZA UNITS: different bolus to basal insulin dose ratio at Week 17¹

Before AFREZZA (baseline): Patients on usual care (which includes rapid-acting analog bolus insulin) had a ~50/50 bolus-to-basal insulin ratio

AFREZZA at Week 17: Titrated dose was ~70% bolus (in AFREZZA UNITS) to 30% basal insulin

Usual Care baseline and Usual Care Week 17: For those continuing on usual care, the ratio remains consistent at 50% bolus and 50% basal

Bar chart showing that units of AFREZZA had a different bolus to basil insulin dose ratio compared with Usual Care.

Safety

Safety: comparable time in hypoglycemic range observed^1††

Bar chart showing that comparable time in hypoglycemic range was observed between the AFREZZA and Usual Care groups at baseline and Week 17.

No significant change in pulmonary function¹

FEV₁ showed no significant difference between groups at 17 weeks

Bar chart showing that pulmonary function (FEV1) showed no significant difference between the AFREZZA and Usual Care groups at 17 weeks (range: 2.84 to 2.93).

Adverse events^1‡‡

Table listing adverse events occurring in each treatment group between randomization and 17 weeks post-randomization: severe hypoglycemia (n=1 in AFREZZA group), diabetic ketoacidosis (n=0), and other serious adverse events (n=2 in Usual Care group)

Treatment-emergent adverse events:

Cough is the most commonly reported AE in the AFREZZA group (14 of 62)
Only other TEAE >5% was shortness of breath (5 of 62)

Individualized Insulin Therapy

Individualized insulin therapy for your patient: a possible scenario based on INHALE-3 study design and results^1,3

Decision-tree schematic depicting a hypothetical scenario for individualized insulin therapy with AFREZZA based on INHALE-3 findings.

A1C=glycated hemoglobin; AID=automated insulin delivery; BG=blood glucose; CGM=continuous glucose monitor; FEV₁=forced expiratory volume in one second; MDI=multiple daily injections; PLG=predictive low-glucose suspend technology; SC RAI=subcutaneous rapid-acting insulin; TIR=time in range; T1D=type 1 diabetes.

References: 1. Data on File (INHALE-3 Clinical Study Report 2024). MannKind Corporation. 2. ClinicalTrials.gov identifier: NCT05904743. 3. American Diabetes Association Professional Practice Committee. Diabetes Care. 2024; 47 (Supplement_1): S158-S178.

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.