Valencia-based MannKind Corp. announced results of two late-breaking posters and four additional analyses of Afrezza® (insulin human) Inhalation Powder, including three posters demonstrating a faster onset of action and a shorter duration than rapid-acting insulin analogs in patients with diabetes mellitus. These data were presented at the American Diabetes Association’s 76th Scientific Sessions (ADA). Afrezza, approved by the FDA in 2014 to improve glycemic control in adult patients with type 1 and type 2 diabetes mellitus, is the only inhaled insulin product available in the U.S.

A randomized, controlled, six-treatment, crossover dose-response study (Poster #100-LB) comparing Afrezza to the rapid-acting insulin analog, Lispro, in 30 patients with type 1 diabetes was presented as a late-breaking poster. Results for doses matched to provide the same GIR-AUC (activity parameter) demonstrated:

* Onset of action within 16 to 21 minutes for Afrezza compared to 45 to 52 minutes for subcutaneous insulin across studies

* Afrezza’s duration of action at clinically relevant doses was consistently shorter by 2 to 3 hours

* Afrezza’s labeled dose overestimates its effect reinforcing the need for appropriate dose titration

Similar results were presented in Poster# 975-P and in a separate meta-analysis of three open-label clamp trials (Poster #931-P) comparing the onset of action of Afrezza with that of subcutaneous Lispro or regular human insulin, which showed onset of action (time to 10% GIR-AUC 0-240) with Afrezza was faster at 25 to 34 minutes compared to 53 to 60 minutes with Lispro.

These data highlight the faster onset of action of Afrezza compared with subcutaneous insulins is relevant for optimal dosing, and supports Afrezza’s use for rapidly controlling elevated glucose levels.

Many people with type 1 diabetes and progressed type 2 diabetes inject rapid-acting insulin analogs to address rising blood sugar levels caused by food.i Hypoglycemia, a dangerous condition that occurs when blood sugar levels drop too low, can be a concern when the effects of rapid-acting insulin analogs extend past mealtime and food absorption. Insulin-related hypoglycemia resulted in nearly 100,000 hospital visits per year in the U.S. between 2007 and 2011, with a cost of $600 million during that five-year period.ii

“When administering an inhaled rapid-acting insulin or an injectable rapid-acting insulin analog, it is critical to strike the balance of providing prandial glucose control while minimizing the risk for post-prandial hypoglycemic events,” said Raymond W. Urbanski, MD, PhD, Chief Medical Officer of MannKind. “These data show Afrezza begins to work in the body more rapidly and leaves the bloodstream more quickly than an injectable rapid-acting insulin analog, which could translate into more flexibility in the timing of administration and a lower potential for hypoglycemic episodes following meals.”

Additional data presented in Poster #100-LB shed light on the dosing of Afrezza relative to subcutaneous rapid-acting insulin. Though no single conversion factor could fully describe the effect, it was noted that the faster response and shorter duration were maintained across matched dosing. As a result, investigators on the late-breaking study reinforced the importance of dose titration for each patient. Based on pharmacokinetic and pharmacodynamic data, it was observed that a 4 unit Afrezza cartridge provides approximately the same insulin exposure as 3.1 IU Lispro.

“There can be significant variability in the way individuals respond to any insulin treatment, often resulting in difficulty with dose selection or a perceived lack of response,” said Tim Heise, MD, of the Profil Institute for Clinical Research in Germany and a study investigator. “The findings presented at ADA are important in helping physicians understanding how to dose and titrate Afrezza in order to maintain optimal insulin response and glucose control.”

Two additional analyses looking at pulmonary function tests from 4,271 patients (Posters #937-P and #973-P) showed that baseline FEV1, a common measure of lung function, was not correlated with the proportion of patients experiencing hypoglycemia, reporting cough or reaching A1C targets with Afrezza. The analyses also showed:

* A pooled analysis of seven studies demonstrated slightly greater declines in pulmonary function (FEV1) in those treated with Afrezza compared with comparator treatments (oral antidiabetic medications or insulin therapy) during the first three months (approximately 30 to 40 mL difference)

* After three months, the change in pulmonary function was similar to comparators up to 24 months

* FEV1 reductions were small in both Afrezza and comparator groups; they represented a small fraction of pulmonary capacity, and the observed treatment group difference disappeared within one month of cessation of Afrezza therapy

“Afrezza fills an important role in the management of blood sugar for people with diabetes, and MannKind is devoted to ensuring patients who can benefit from it are aware that it is available and that their doctors are appropriately trained on how to use it,” said Matthew Pfeffer, Chief Executive Officer of MannKind. “When we relaunch next month, we will be pulling from nearly two years of learnings related to patient selection, access and titration, in order to simplify the process of getting this important treatment option into the hands of individuals with diabetes.”

MannKind recently reacquired the rights to Afrezza and will be launching its own fully integrated commercialization infrastructure along with MannKind-branded supply of the treatment in July. Patients and healthcare providers should be aware that MannKind is committed to ensuring Afrezza remains available to diabetes patients in the United States with no disruptions in access. In addition, MannKind earlier this week announced a new collaboration with JDRF to advance therapies for all patients with type 1 diabetes.