Michael Haller, MD, discusses inhaled insulin and Afrezza data for type 1 diabetes

On August 6, 2025, MannKind Corporation submitted a supplemental Biologics License Application to the FDA for its inhaled insulin Afrezza for a pediatric population indication, with a decision expected early in the fourth quarter of 2025, according to a financial report from the company.¹

The filing was based on data from the INHALE-1 study, led by Michael Haller, MD, MS-CI, lead author of the study and professor and chief of Pediatric Endocrinology at the University of Florida. The study evaluated the safety and efficacy of the inhaled insulin regimen as a replacement for rapid-acting meal insulin in children with type 1 diabetes (T1D). It included 230 patients aged 4 to 17 years, who were randomized to either inhaled insulin or rapid-acting analogue for meals, with a primary outcome of change in A_1C at 26 weeks.²

According to a press release from the American Diabetes Association's 85th Scientific Session, where data were presented at the June meeting in Chicago, findings indicated that inhaled insulin is safe and effective in children with T1D. Full study results, including a safety extension, have been submitted for presentation at a medical meeting sometime in the second half of 2025, according to MannKind.¹

"The primary outcome essentially showed non-inferiority of inhaled insulin compared to rapid-acting injected insulin," stated Haller in the video above. "This finding is slightly qualified by the inclusion of 1 patient who was highly non-adherent to their insulin regimen and was assigned to the inhaled insulin group. Including this patient in the analysis resulted in a non-significant p-value for non-inferiority. However, in a sensitivity analysis excluding this non-adherent [patient], the inhaled and injected insulin groups showed nearly identical outcomes in terms of hemoglobin A_1C."

Currently, Afrezza is being prescribed off-label for the pediatric population, with the adult population being the only FDA-approved indication for the inhaled insulin. Now, with a filing submitted to the federal agency, Afrezza is one step closer to a proper label pediatrics.

"The field has long been in search of more rapid-acting insulins—truly rapid insulins—that can more physiologically cover meal excursions and corrections and reduce risk for post-meal hypoglycemia," added Haller. "In terms of injectable insulins, we've made some progress by manipulating the insulin structure so it gets into the bloodstream faster, but again, it's just not fast enough."

"Essentially, this is a biomaterial technosphere that gets bound to regular human insulin," Haller explained of Afrezza. "So, it's your non-manipulated insulin, and then, when it's inhaled into the lung, these particles dissociate, and the insulin is absorbed very rapidly through the lung blood vasculature, allowing the insulin to reach peak levels within 15 or 20 minutes. So, much closer to the way a human pancreas that's working should work. Because of that, it really can provide more optimal meal coverage, safer control of hyperglycemic corrections, and it's much better for athletes in terms of not having hypoglycemia associated with insulin dosing."

Haller added that until there is a wider shift in how T1D treatment is looked at, utilization rates, even among adults, could be lower compared to other T1D insulin options.

"It's been successful in adults, although it remains fairly underutilized, I would say, just because the paradigm hasn't shifted so that people think of using inhaled insulin as a first option. Everybody still kind of assumes we have to use injected," he said. "Current pediatric use is off-label, and myself and many others are prescribing it that way. Lots of pediatric medicine is off-label, unfortunately."

References:

1. MannKind Corporation reports second quarter 2025 financial results and provides business update. MannKind Corporation. Press release. August 6, 2025. Accessed August 7, 2025. https://investors.mannkindcorp.com/news-releases/news-release-details/mannkind-corporation-reports-second-quarter-2025-financial
2. Inhaled insulin shown as a safe and effective replacement for standard-of-care in children with type 1 diabetes. American Diabetes Association. Press release. June 22, 2025. Accessed August 7, 2025. https://professional.diabetes.org/sites/dpro/files/2025-06/ADA_InhaledInsulinPressRelease_FINAL.pdf