With a PDUFA date on the horizon, another trial of Afrezza begins

With an important FDA approval decision scheduled for late May, the maker of an inhaled insulin product recently announced that the investigators had enrolled the first participant in a study of the product in older children and adolescents who had been newly diagnosed Type 1 diabetes.

The target decision date — known as the Prescription Drug User Fee Act, or PDUFA date — for the inhaled insulin product is May 29, 2026. That decision will be about whether to approve the inhaled insulin produced, marketed as Afrezza, for children and adolescents living with Type 1 or Type 2 diabetes. To make that decision, the agency is considering evidence collected from a different study, called INHALE-1, a phase 3, open-label, randomized clinical study that compared Afrezza in combination with a basal insulin with insulin aspart, insulin lispro or insulin glulisine, also in combination with a basal insulin. Results of the INHALE-1 study published in January 2026 in the journal Diabetes Care showed that Afrezza did not meet the primary end point of noninferiority with respect to hemoglobin A1c, but the investigators noted greater treatment satisfaction among those in the Afrezza group and also less weight gain.

Afrezza was approved by the FDA for adults in 2014. Approvals, clinical trials and possible use in children and adolescents is a new chapter for the drug and its maker, MannKind Corporation. Other MannKind products FDA-approved and on the market include an insulin patch, called V-Go; Tyvaso (treprostinil), an inhaled treatment for pulmonary arterial hypertension; and Furoscix (furosemide), a version of the commonly prescribed diuretic that is delivered subcutaneously rather than orally as a pill

The trial that the first patient was enrolled in is called INHALE-1st. It is a phase 3, single-arm study evaluating the safety and efficacy of Afrezza in combination with subcutaneously injected basal insulin. The study subjects are older children and teens, ages 10 to less than 18 years, with newly diagnosed, stage 3 type 1 diabetes. Stage 3 is the stage at which symptoms appear and currently is the stage at which most cases of Type 1 are diagnosed. According to the summary of the trial on clinicaltrials.gov, the study is also designed to assess the satisfaction of patients and parents or “legally authorized representatives.” The study design calls for investigators to follow the participants for 13 weeks, followed by an optional extension period.

According to the company news release, which was issued on Feb. 9, the first patient was enrolled at the Barbara Davis Center for Diabetes in Aurora, Colorado, one of the approximately 10 sites where patients will be enrolled.

The news release says that the Jaeb Center for Health Research, a nonprofit coordinator of studies of eye disorders and Type 1 diabetes in Tampa Florida, is leading the INHALE-1st study. The news release quotes the center’s medical director, Roy W.Beck, M.D., Ph.D., as saying that one of his children developed Type 1 diabetes. “I know firsthand how overwhelming it is to find out that your child has been diagnosed with diabetes and has to start giving injections of insulin multiple times a day,” Beck said. “The study will help evaluate whether replacing most of the injections with inhalations of insulin may lessen that burden for children and their families as they adjust to managing a lifelong disease.”

Many of the innovations that transformed diabetes care, such as continuous glucose monitors (CGMs) and insulin pumps, have shown their full value and impact in the pediatric patients, Michael Castagna, Pharm.D., MannKind’s CEO, said in the news release. “With nearly a decade of safety and real-world adult experience behind Afrezza, INHALE-1st gives us an important opportunity to assess use earlier in the treatment journey for youth at the time of diagnosis so patients can potentially improve management of their mealtime glucose,” Castagna said.

Beck was the corresponding author of a study of Afrezza in adults published in Diabetes Care in December 2024 that showed that a regimen of Afrezza and degludec, a long-acting insulin sold under the brand name Tresiba, was noninferior to “usual care,” which consisted of an automated insulin delivery system or multiple daily insulin injections with continuous glucose monitoring.

Beck and his co-authors noted that Afrezza is not frequently prescribed, even though it was approved 10 years ago. They said the lack of use may be due to limited clinical trial data about a dose that is more bioequivalent to the rapid-acting insulin analogs — insulin aspart, insulin lispro or insulin glulisine — that are commonly used to tamp down after-meal spikes in blood glucose.

Beck and his colleagues also mentioned the dearth of data that compare Afrezza, used in conjunction with long-acting basal insulin plus continuous glucose monitoring for dosing determinations, with contemporary insulin delivery methods, including automated delivery.