Afrezza (recombinant human insulin inhalation) / MannKind - LARVOL DELTA

Cost-Effectiveness Analysis of Technosphere Insulin (TI) Versus Insulin Aspart Injection in Type 1 Diabetes Management: Perspective From the US Healthcare System (ISPOR 2025) - "Based on results obtained from 171 trial, TI appears to be a cost-effective alternative to insulin aspart, offering potential long-term cost savings and improved health outcomes by potentially reducing hypoglycemic events."

Cost effectiveness • HEOR • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Squamous Cell Carcinoma of the Lung in a Patient Using Inhaled Insulin: A Case Report and Review of Pulmonary Safety Concerns (ENDO 2025) - "While SCC is linked to smoking and environmental factors, studies suggest Afrezza, an inhaled insulin introduced in 2014, may also pose risks...https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022472lbl.pdf*. .*"

Case report • Clinical • Review • Clear Cell Renal Cell Carcinoma • Cough • Diabetes • Genito-urinary Cancer • Lung Cancer • Metabolic Disorders • Oncology • Pain • Pulmonary Disease • Renal Cell Carcinoma • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • Type 1 Diabetes Mellitus

Efficacy and Safety of Prandial Technosphere Inhaled Insulin (Afrezza) Compared with Placebo in Adult Individuals with T2DM—Results from a Phase III Clinical Trial from India (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Clinical • P3 data • Metabolic Disorders • Type 2 Diabetes Mellitus

Patient-Reported Outcomes with Use of Inhaled Technosphere Insulin (TI) (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Clinical • Patient reported outcomes • Metabolic Disorders

Inhaled Technosphere Insulin (TI) vs. Rapid-Acting Analogue (RAA) Insulin in Children Using Multiple Daily Injections (MDI)—INHALE-1 [WITHDRAWN] (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Clinical • Metabolic Disorders

COMPARISON OF A REGIMEN OF INHALED TECHNOSPHERE INSULIN PLUS INSULIN DEGLUDEC VERSUS USUAL CARE IN ADULTS WITH TYPE 1 DIABETES (T1D) (ATTD 2025) - "Treatment group difference in time <54 mg/dL was 0.2% (95% CI -0.1% to 0.5%). Conclusions Switching from insulin delivery with predominately AID or MDI to a regimen of TI and degludec was non-inferior for TIR and showed an improvement in HbA1c."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

INHALE-AIDEx: Evaluating the Effect of Inhaled Technosphere Insulin Vs Rapid Acting Analogue Insulin on Exercise-Induced Hypoglycemia in Adults with Type 1 Diabetes Using Automated Insulin Delivery (clinicaltrials.gov) - P=N/A | N=30 | Not yet recruiting | Sponsor: Jaeb Center for Health Research

New trial • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

A 13-Week Single-Arm Evaluation of Inhaled Technosphere Insulin Plus Insulin Degludec for Adults with Type 1 Diabetes. (PubMed, Diabetes Technol Ther) - " In adults with T1D, glycemic outcomes were comparable or slightly better with TI-degludec after switching from AID or MDI. TI should be considered as an option for individuals who want an alternative to using an insulin pump or MDI for insulin delivery."

Clinical • Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

What's new in pulmonary inhaled insulin? (ATTD 2025) - "Technosphere insulin (TI) was approved over a decade ago yet best use practices and who are the best candidates for its use is not well understood. INHALE-3 is a 123 subject study where 62 and 61 were randomized to the TI /degludec and usual care (UC) groups, respectively (mean baseline A1C 7.6%)...Those both on MDI and AID decided to stay on TI for various reasons, but not carrying additional diabetes equipment, long-term skin problems, and easier to exercise without hypoglycemia were the most common. In conclusion, TI is another option for prandial insulin use, including those not satisfied with AID."

Diabetes • Hypoglycemia • Metabolic Disorders

SUSTAINED BENEFIT FROM USE OF INHALED INSULIN IN THE INHALE-3 EXTENSION STUDY (ATTD 2025) - "Background and Aims In the INHALE-3 randomized trial of adults with type 1 diabetes, inhaled Technosphere Insulin (TI) was shown to be superior to rapid acting analogue (RAA) insulin in reducing post-prandial hyperglycemia, and 17-week HbA1c levels with a regimen of TI plus insulin deglucec were non-inferior compared with a control group using RAA insulin with automated insulin delivery or multiple daily injections. Following the randomized trial, the TI group continued to use TI and degludec for an additional 13 weeks to assess sustainability of effect without intervening clinic visits...CGM metrics did not change substantially from 17 weeks to 30 weeks (Table). Conclusions In the INHALE-3 trial, HbA1c improved between 17 and 30 weeks despite there being no scheduled study visits or contacts This durable effect suggests that over time participants learned how to better optimize use of TI dosing for meals and corrections."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

POST-PRANDIAL GLUCOSE EXCURSION WITH INHALED INSULIN IN YOUTH COMPARED WITH ADULTS WITH TYPE 1 DIABETES (ATTD 2025) - "Background and Aims Inhaled Technosphere insulin (TI) has been shown to reduce post-prandial glucose excursions in adults with type 1 diabetes (T1D)...Results Mean (±SD) glucose excursion was less with TI (69±56 mg/dL in youth and 73±50 mg/dL in adults) compared with RAA in adults (101±45 mg/dL); and time to peak glucose was shorter with TI (69±34 in youth and 71±36 minutes in adults) than with RAA (78±31 minutes in adults) as seen in the Figure. Conclusions The post-prandial glucose excursion with TI appears similar in youth to that which has been reported in adults and is substantially lower than the excursion following a bolus with RAA insulin."

Clinical • Diabetes • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus

Inhaled Technosphere Insulin Plus Insulin Degludec for Adults with Type 1 Diabetes: The INHALE-3 Extension Study. (PubMed, Diabetes Technol Ther) - " HbA1c levels were sustained over 30 weeks using a TI-degludec regimen after switching from AID or MDI. TI should be considered an option for people with T1D."

Clinical • Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Inhaled insulin in pediatrics (INHALE-1 - Peds Study) (ATTD 2025) - "Objective: To evaluate the efficacy and safety of Afrezza, an inhaled technosphere insulin (TI) versus subcutaneous rapid-acting analog (RAA) insulin in children with type 1 diabetes... Observed dosing for a standardized meal with TI resulted in significantly reduced post-meal glucose excursions versus RAA. TI may be an important alternative to injected RAA insulin for glycemic control in children with T1D offering reduced glycemic excursion following a standardized meal"

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

INHALE-GDM: Inhaled Insulin Vs Rapid-acting Injections for Post-meal Glucose Control in Women with Gestational Diabetes (clinicaltrials.gov) - P2/3 | N=30 | Not yet recruiting | Sponsor: Jaeb Center for Health Research | Trial completion date: Dec 2024 ➔ May 2025 | Initiation date: Sep 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2024 ➔ May 2025

Trial completion date • Trial initiation date • Trial primary completion date • Diabetes • Gestational Diabetes • Metabolic Disorders

MannKind Showcases Efficacy, Safety, and Mealtime Control Data from Recent Pediatric and Adult Studies of Afrezza at the ATTD Conference, March 19-22 (GlobeNewswire) - "An sNDA filing for Afrezza in pediatric population anticipated in 2025....MannKind...will showcase data from recent studies of inhaled insulin across five presentations at the 18th International Conference on Advanced Technologies and Treatments for Diabetes to be held March 19-22 in Amsterdam....'Data from both the INHALE-1 pediatric and INHALE-3 adult studies continue to drive groundbreaking conversations around inhaled insulin,..."

Clinical data • FDA filing • Type 2 Diabetes Mellitus

MannKind Corporation Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Requested meeting with the U.S. Food and Drug Administration ('FDA') in 1H 2025 to discuss data submission for potential approval of Afrezza in the pediatric population. Expect twelve-month data set with safety extension in 1H 2025. Anticipate supplemental new drug application filing in 1H 2025 pending FDA feedback. Clofazimine Inhalation Suspension Phase 3 (ICON-1) global clinical trial (MNKD-101)...Expect to meet the interim enrollment target by YE 2025....Nintedanib DPI Phase 1 clinical trial (MNKD-201)...Expect to meet with the FDA in 1H 2025 to advance MNKD-201 into next phase of development..."

Enrollment status • FDA event • Idiopathic Pulmonary Fibrosis • Nontuberculous Mycobacterial Disease • Type 2 Diabetes Mellitus

A Randomized Trial Comparing Inhaled Insulin Plus Basal Insulin Versus Usual Care in Adults With Type 1 Diabetes. (PubMed, Diabetes Care) - "In adults with type 1 diabetes, HbA1c after 17 weeks with a regimen of TI and degludec was noninferior to UC, which consisted predominately of either AID or MDI. TI should be considered an option for people with type 1 diabetes, particularly those who are motivated to further reduce postprandial hyperglycemia."

Journal • Cough • Diabetes • Metabolic Disorders • Respiratory Diseases • Type 1 Diabetes Mellitus

INHALE-GDM: Inhaled Insulin vs Rapid-acting Injections for Post-meal Glucose Control in Women With Gestational Diabetes (clinicaltrials.gov) - P2/3 | N=30 | Not yet recruiting | Sponsor: Jaeb Center for Health Research

New P2/3 trial • Diabetes • Gestational Diabetes • Metabolic Disorders

A Randomized Comparison of Postprandial Glucose Excursion Using Inhaled Insulin Versus Rapid-Acting Analog Insulin in Adults With Type 1 Diabetes Using Multiple Daily Injections of Insulin or Automated Insulin Delivery. (PubMed, Diabetes Care) - "Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users."

Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

MKC-TI-193: INHALE-3: Afrezza® Combined With Insulin Degludec Versus Usual Care in Adults With Type 1 Diabetes (clinicaltrials.gov) - P4 | N=141 | Completed | Sponsor: Mannkind Corporation | Active, not recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Jun 2024

Trial completion • Trial completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

An in-silico modeling approach to separate exogenous and endogenous plasma insulin appearance, with application to inhaled insulin. (PubMed, Sci Rep) - "A three-step dynamic in-silico modeling approach was developed to estimate the two insulin contributions of total plasma insulin in a group of 21 healthy subjects who underwent two equivalent standardized meal tests on separate days, one of which preceded by inhalation of a Technosphere® Insulin dose (22U or 20U)...The percentage of exogenous insulin reaching the plasma, relative to the inhaled dose, was 42 ± 21%. The proposed in-silico approach separates exogenous and endogenous insulin contributions to total plasma insulin, provides individual bioavailability estimates, and can be used to assess the effect of inhaled insulin on endogenous insulin secretion during a meal."

Journal

Prandial Insulins: A Person-Centered Choice. (PubMed, Curr Diab Rep) - "In contrast, rapid-acting analogs, such as lispro, aspart, and glulisine, are new insulin types with amino acid modifications that enhance their subcutaneous absorption, resulting in a faster onset and shorter action duration. Ultra-rapid analogs, like faster aspart and ultra-rapid lispro, offer even shorter onset of action, providing better meal-time flexibility. The Technosphere insulin offers an inhaled route for prandial insulin delivery...Ongoing research is focused on refining prandial insulin replacement and exploring newer delivery methods. The article provides a comprehensive overview of various prandial insulin options and their clinical applications in the management of diabetes."

Journal • Review • Diabetes • Hypoglycemia • Metabolic Disorders

Afrezza® INHALE-1 Study in Pediatrics (clinicaltrials.gov) - P3 | N=319 | Active, not recruiting | Sponsor: Mannkind Corporation | Recruiting ➔ Active, not recruiting | Trial primary completion date: Feb 2024 ➔ Sep 2024

Combination therapy • Enrollment closed • Trial primary completion date • Diabetes • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

POSTPRANDIAL GLUCOSE FOLLOWING A BOLUS WITH INHALED INSULIN VERSUS USUAL CARE (ATTD 2024) - "Background and Aims: Technosphere Insulin is an ultra-rapid-acting inhaled insulin... Expected conclusion to include summary of results highlighting the efficacy and safety outcomes."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Afrezza® INHALE-1 Study in Pediatrics (clinicaltrials.gov) - P3 | N=264 | Recruiting | Sponsor: Mannkind Corporation | Trial completion date: Apr 2024 ➔ Apr 2025

Combination therapy • Trial completion date • Diabetes • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus