MannKind Announces FDA Acceptance of sBLA for Afrezza in Pediatric Diabetes Patients

Analysis reveals significant industry trends and economic implications

Release Date

2025-10-14

Category

Drug Approval Event

Reference

Source

Breakthrough Clinical Results

MannKind Corporation announced that the FDA has accepted its supplemental Biologics License Application (sBLA) for Afrezza (insulin human) Inhalation Powder for children and adolescents aged 4-17 years living with type 1 or type 2 diabetes. The sBLA is based on data from the Phase 3 INHALE-1 study, which evaluated Afrezza in combination with basal insulin versus multiple daily injections (MDI) with basal insulin. The FDA has assigned a PDUFA target action date of May 29, 2026.

Key Highlights

  • FDA accepts sBLA for Afrezza in pediatric diabetes patients aged 4-17.
  • Afrezza could be the first needle-free insulin option for pediatric patients in over 100 years.
  • sBLA submission is based on data from the Phase 3 INHALE-1 study.
  • PDUFA target action date is set for May 29, 2026.

Incidence and Prevalence

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Global Diabetes Estimates: Incidence and Prevalence

The prevalence of diabetes continues to increase worldwide, with diabetes-related macrovascular morbidity and mortality becoming major health care problems. Diabetes mellitus is projected to rank as the seventh leading cause of mortality by 2030 globally, highlighting the growing burden of this condition.

Regional Prevalence Data

United States

In the United States, as of 2021, 38.4 million Americans have diabetes. This represents a significant increase from 2011, when an estimated 26 million persons aged ≥20 years (11.3% of the U.S. population) had diabetes. The prevalence of diabetes is over 50% higher in Latinos than in the general population, with this group also suffering from higher rates of complications and diabetes-related mortality than non-Hispanic whites. Hispanics and non-Hispanic blacks had a greater risk of diabetes than whites, with hazard ratios of 2.25 (95% CI 1.48-3.40) and 1.69 (95% CI 1.11-2.59) respectively.

Africa

Sub-Saharan Africa is predicted to have the steepest increase in the prevalence of diabetes in the next 25 years. In Mozambique, the prevalence of diabetes was 7.4% (95% CI: 5.5-10.0) and impaired fasting glucose was 4.8% (95% CI: 3.6-6.3) in 2014/2015, which was more than twofold higher than in 2005 [2.9% (95% CI: 2.0-4.2) and 2.0% (95% CI: 1.1-3.5) respectively]. Diabetes prevalence in Mozambique was almost double in participants classified with overweight/obesity [10.6% (95% CI: 7.5-14.6)] compared to their leaner counterparts [6.3% (95% CI: 4.0-9.9)]. There were 50% more people with diabetes in urban areas than in rural areas in Mozambique.

Europe

In the Republic of Srpska (Bosnia and Herzegovina), the average incidence of type 1 diabetes in children under 15 years was 19/100,000 (95% CI 13.1-25.0) in the period 2017-2022, compared to 11/100,000 in 2001-2016. The highest incidence was 28.7/100,000 in 2020, the first year of the global COVID-19 pandemic. The Republic of Srpska has entered the group of countries with high-risk for diabetes with an incidence of 19.4/100,000.

Risk Factors and Patterns

Several patterns emerge from the global data:

  1. Urban vs. Rural: Higher prevalence in urban areas compared to rural settings
  2. Weight Association: Significantly higher rates among those with overweight/obesity
  3. Ethnic Disparities: Certain ethnic groups face disproportionately higher risks
  4. Temporal Trends: Consistent increases in prevalence over time across regions

The global diabetes epidemic continues to evolve, with concerning trends of increasing prevalence across diverse populations and geographic regions.

Study Design Parameters

Study Design Parameters and Endpoints in Key Diabetes Trials

Study Designs

Randomized controlled trials (RCTs) are the predominant design in diabetes research, including patient-preference equivalence trials, double-blinded trials, and open-label studies. Recent trials have employed various approaches:

  • A 2023 study randomized 120 people with type 2 diabetes into four parallel groups for 32 weeks: semaglutide (open label), empagliflozin (blinded), their combination, and placebo
  • The IMAGINE program included more than 6000 patients with ~3900 receiving basal insulin peglispro (BIL)
  • Cross-sectional designs evaluate quality of life in diabetic patients with complications
  • Crossover designs are used particularly for comparing different treatment devices
  • Qualitative participant interviews provide context to endpoint improvements
  • Quality improvement interventional studies develop and evaluate new diabetic algorithms

Trial durations typically range from 3-6 months for early outcomes to several years (median 4.5 years in some studies) for long-term outcomes.

Participant Selection

Eligibility criteria commonly include: - Age ranges (e.g., 40-80 years or 26-60 years) - HbA1c levels (e.g., ≤7.5% or <10%) - Blood pressure parameters (e.g., systolic ≤145 mmHg) - Cholesterol levels (e.g., total ≤5.2 mmol/l) - Duration of diabetes (e.g., more than one year) - Treatment by a general practitioner - Insulin treatment status (often excluded in some studies) - High risk of CVD (in some studies)

Primary Endpoints

Key primary endpoints include:

  • Glycemic control measures: HbA1c reduction, time in target glucose range, time below range (<70 mg/dL), glycemic variability
  • Cardiovascular outcomes: major adverse cardiovascular events (MACEs), composite of all-cause death and cardiovascular events
  • Cardiometabolic control equivalence between monitoring frequencies
  • Kidney oxygenation and arterial stiffness measured by MRI
  • Rates of nocturnal hypoglycemia
  • Patient-reported outcomes (PROs): quality of life and psychological well-being

Secondary Endpoints

Secondary endpoints are diverse:

  • Metabolic parameters: Blood pressure, cholesterol levels, body mass index, liver fat, triglycerides
  • Kidney function: GFR, urine albumin/creatinine ratio (UACR), kidney perfusion
  • Blood markers: Erythropoietin levels, hematocrit, alanine aminotransferase (ALT)
  • Treatment-related: Injection site reactions, adherence to medications, satisfaction with treatment
  • Lifestyle factors: Smoking behavior, physical activity
  • Economic measures: Loss of work due to illness, supply costs, cost-effectiveness
  • Safety outcomes: Severe hypoglycemia episodes, diabetic ketoacidosis events

Analysis Methods

Trials employ various analytical approaches:

  • Intention-to-treat analysis with repeated measures
  • ANCOVA for outcomes with only baseline and final measurements
  • Cost-minimisation analysis or incremental cost-effectiveness analysis
  • Meta-regression to evaluate interventions
  • Latent profile analysis to classify patients into homogeneous groups
  • One-stage individual participant data meta-analyses and network meta-analyses
  • Subgroup analyses by age, follow-up length, treatment intensity, and diabetes duration

Recent trials increasingly incorporate technology assessment and equity considerations using frameworks like PROGRESS to assess health inequality.