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

INHALE-1st: Afrezza® For Youth With Newly-Diagnosed Type 1 Diabetes (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Mannkind Corporation

New P2 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

MannKind Announces U.S. FDA Accepts for Review its Supplemental Biologics License Application (sBLA) for Inhaled Insulin (Afrezza) in Children and Adolescents Aged 4-17 Years Living with Diabetes (GlobeNewswire) - "The application has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of May 29, 2026...The sBLA is based on results from the Phase 3 INHALE-1 study in children and adolescents between the ages of 4-17 who are living with either type 1 or type 2 diabetes....The submission also included safety data from the study’s 26-week extension phase in which all remaining MDI patients switched to Afrezza. Full results will be shared at the International Society for Pediatric and Adolescent Diabetes (ISPAD) in early November."

FDA filing • P3 data • PDUFA • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

MannKind Completes Acquisition of scPharmaceuticals, Accelerating Revenue Growth in Cardiometabolic Care (Mannkind Corp Press Release) - "The transaction will strengthen MannKind’s commercial and medical capabilities by integrating scPharmaceuticals’ experienced team into its existing infrastructure. MannKind is positioned as a diversified, growth-focused biopharmaceutical company with its commercial assets—Afrezza, FUROSCIX and V-Go -- along with Tyvaso DPI-related revenues, contributing to an annualized run rate of over $370 million based on Q2 2025 results. Additionally, the FUROSCIX ReadyFlow Autoinjector supplemental New Drug Application (sNDA) filing was submitted as planned in Q3 2025."

M&A • Pulmonary Arterial Hypertension • Type 2 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) - "Given these risks, clinicians should carefully consider alternative treatments for patients with lung disease or cancer risk factors, monitor pulmonary health regularly, and educate patients about potential symptoms. Further research is needed to establish a definitive causal relationship and understand the long-term safety of Afrezza."

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) - "TI(Afrezza®) demonstrated a significant reduction in HbA1c in individuals from India with T2DM with no significant differences in lung function observed compared to placebo group. This study reaffirms TI as an effective and safe treatment option for T2DM management."

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

Patient-Reported Outcomes with Use of Inhaled Technosphere Insulin (TI) (ADA 2025) - "Introduction and Objective: The INHALE-3 randomized trial (N=123) demonstrated HbA1c levels with a regimen of TI plus insulin degludec were non-inferior compared with a usual-care control group (about half using AID and half MDI). Participants who had poorer glycemic control and greater dissatisfaction with diabetes and with their insulin regimen at baseline showed more improvement in glycemic control and PROs, perhaps reflecting a greater openness to trying a different insulin delivery regimen."

Clinical • Patient reported outcomes • Diabetes • Hypoglycemia • Metabolic Disorders

Inhaled Technosphere Insulin (TI) vs. Rapid-Acting Analogue (RAA) Insulin in Children Using Multiple Daily Injections (MDI)—INHALE-1 [WITHDRAWN] (ADA 2025) - No abstract available

Clinical • Metabolic Disorders

Safety and Efficacy of Inhaled Technosphere® Insulin in the Postprandial Period With Modified Initial Dose Conversion. (PubMed, Diabetes Ther) - P4 | "TI group demonstrated a more favorable glycemic response in the 2-h postprandial period vs AID control. Data from this and previous studies suggest this higher modified conversion TI dose from subcutaneous RAA may help further reduce postprandial hyperglycemia in T1D."

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

INHALE-AIDEx: Effect of Inhaled Technosphere Insulin vs RAA Insulin on Exercise-Induced Hypoglycemia in Adults With T1D Using Automated Insulin Delivery (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: Jaeb Center for Health Research | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Technosphere insulin in the treatment of Type 1 diabetes mellitus: A systematic review and meta-analysis. (PubMed, J Diabetes Complications) - "The use of Technosphere Insulin (TI) in T1DM patients did not show a difference in HbA1c, suggesting that TI may offer advantages in weight stability and a lower incidence of hypoglycemic events compared to rapid-acting insulin (RAI)."

Journal • Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus

Inhaled Insulin Dosing in a Randomized Trial in Adults with Type 1 Diabetes (T1D) (AACE 2025) - "Technosphere Insulin (TI) is an ultra-rapid-acting inhaled insulin available in single-use cartridges of 4, 8, and 12 units. The TI United States Prescribing Information (USPI) recommends a conversion of subcutaneous rapid-acting insulin analogue (RAA) units rounded up to nearest TI cartridge dose."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

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

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

Enrollment open • Diabetes • Gestational Diabetes • Metabolic Disorders

Afrezza® INHALE-1 Study in Pediatrics (clinicaltrials.gov) - P3 | N=319 | Completed | Sponsor: Mannkind Corporation | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Pediatrics • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

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