The ADA is currently holding their annual scientific sessions. I came across some sessions on Afrezza that I thought were interesting.
I think that if Mannkind can show that Afrezza is safe for children, many more people would be willing to use it. So I’m particularly interested in the final results of that study. They presented some results at the scientific sessions. I’m pasting the full abstracts of the 3 presentations related to Afrezza below. The A1c improvement for Type 2 patients is pretty incredible.
Safety and Pharmacokinetics of Technosphere Insulin in Pediatric Patients
Author Block: MARSHALL L. GRANT, JOHN A. KRUEGER, MARK FINEMAN, GAURAV SHARMA, FRANK POMPILIO, DAVID M . KENDALL , Westlake Village , CA , San Diego , CA
Technosphere Insulin (TI) is an ultra-rapid, short-acting inhaled insulin that provides glycemic control in patients with diabetes. This ongoing, 2-part, open-label, interventional study aims to assess the efficacy and safety of TI in children aged 4 to 17 years with type 1 diabetes mellitus (T1DM) who are on a stable regimen of basal-bolus insulin therapy. Part 1 is a single-arm study that includes evaluation of insulin pharmacokinetics (PK) after a single prandial dose of TI (4, 8, or 12 units), followed by a 4-week titration period. Approximately 46 patients will be enrolled across 3 age cohorts: cohort 1 (13-17 years), cohort 2 (8-12 years), and cohort 3 (4-7 years). As of August 16, 2018, 15 patients had enrolled in cohort 1, 14 had received at least 1 dose, and 8 completed the titration period. Overall, 50% of the safety population (n=14) was female, mean duration of T1DM was 6.2 years, mean age was 15 years, and mean body mass index was 22.4 kg/m2. Initial PK results from cohort 1 demonstrated insulin metabolism similar to that in adult patients receiving TI. Insulin concentrations rapidly increased in the first 30 minutes after TI treatment and returned to baseline by 120 minutes for the 4-, 8-, and 12-unit doses. Mean postprandial glucose levels decreased within 1-hour postdose for the 8- and 12-unit dose groups. Seven patients developed treatment-related cough of mild (6 events) or moderate (1 event) severity. Seven patients experienced a total of 41 hypoglycemic events, but no patient required the assistance of another person to administer corrective carbohydrates. No clinically relevant declines in pulmonary function were reported. Two patients discontinued the study due to adverse events (cough, diabetic ketoacidosis). These data will help determine the appropriate age range for inclusion and recommended dosing for part 2, which will be a 1-year efficacy and safety study.
Technosphere Insulin Provides Better Early Postprandial Glucose Control than Subcutaneous Rapid-Acting Analog
Author Block: MARSHALL L. GRANT, FRANK POMPILIO, GAURAV SHARMA, JOHN A. KRUEGER, DAVID M . KENDALL , NADIA ZAVERI, Westlake Village , CA
In a recent study (STAT, NCT03143816), patients with type 1 diabetes mellitus (T1DM) treated with Technosphere Insulin (TI) demonstrated better early postprandial glucose (PPG) control than those on subcutaneous (SC) insulin aspart. The average daily dose of TI in patients who took TI as directed in the protocol was twice that of aspart (40.5 vs. 20.6 units). Despite the higher dose, the TI group experienced less time in hypoglycemia than the aspart group. These results prompted a retrospective analysis of mixed-meal tolerance tests (MMTTs) conducted in T1DM to further evaluate the 2:1 dosing ratio.
In study MKC-TI-009 (NCT00308308), patients with T1DM underwent 1 to 3 MMTTs. A total of 1326 PPG profiles were evaluable: 674 MMTTs from 261 patients on SC aspart and 652 MMTTs from 264 patients on TI. On average, the area under the PPG excursion curve (PPGE AUC) decreased with increasing dose, and the mean (SE) ratio of the aspart slope to the TI slope was 2.1 (0.3), consistent with the results of STAT. This was confirmed when doses of TI 8, 16, and 24 units were compared with mean (SE) aspart doses of 4 (1), 8 (1), and 12 (1) units, respectively (Figure).
The PPGE curves confirm the earlier onset and shorter duration of TI, while the tendency to drop below baseline in the late postprandial period reflects the longer duration of action of SC aspart. The timing of hypoglycemia (levels 1 and 2) follows the pattern of PPGEs.
Disclosures: M.L.Grant: Employee; Self; MannKind Corporation, Stock/Shareholder; Self; MannKind Corporation. F.Pompilio: Employee; Self; MannKind Corporation, Stock/Shareholder; Self; Amgen Inc., MannKind Corporation. G.Sharma: Employee; Self; MannKind Corporation. J.A.Krueger: Employee; Self; Eli Lilly and Company, MannKind Corporation, Stock/Shareholder; Self; Eli Lilly and Company. D.M.Kendall: Employee; Self; MannKind Corporation, Employee; Spouse/Partner; Amgen Inc., Stock/Shareholder; Self; MannKind Corporation. N.Zaveri: Employee; Self; MannKind Corporation, Stock/Shareholder; Self; Becton, Dickinson and Company.
Effective Treatment of T2D Patients Uncontrolled on Multiple Diabetes Medications by Adding Afrezza Mealtime Ultra-Rapid Insulin
Author Block: PHILIP LEVIN , LEE A. BROMBERGER, SIMON R. BRUCE, Baltimore , MD , San Diego , CA
Fourteen T2D subjects in a real-world practice setting, uncontrolled on oral/injectable combo therapy (mean A1C 9%), received inhaled human insulin (INH-Afrezza), added to current therapy and titrated weekly for up to 12 weeks. A1C and 2-week continuous glucose monitoring (CGMS) profiles (Libre Pro) were collected at baseline and after 3 months.
All subjects started INH 4 units (u) prior to each meal and titrated rapidly to 12 u/meal over 9 days. Thereafter, INH was adjusted for each meal once weekly, based on PPG at 2-2.5 hours measured on days 1 and 2 of each week, as follows: Add 4 u if PPG > 160 mg/dl, no change if PPG 90-160 mg/dl and decrease by 4 u if PPG < 90 mg/dl. More than 1/2 of subjects were taking basal insulin.
Addition of the only available inhaled ultra-rapid rapid mealtime insulin (Afrezza) lowered glucose safely in patients with T2D inadequately controlled on oral and/or injectable therapy. Initiation and titration, following a simple algorithm, resulted in significant A1c reduction (-1.6%, p<.0001), a decrease in mean daily glucose (~50 mg/dl), and a 76% increase in time-in-range on CGMS, with no significant increase in hypoglycemia (Time<70 mg/dL). No severe hypoglycemia occurred. Final mealtime Afrezza doses achieved were 18, 16 and 20 u at breakfast, lunch, dinner respectively.
Disclosures: P.Levin: Research Support; Self; MannKind Corporation, Novartis AG, Novo Nordisk Inc., Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck & Co., Inc., Sanofi. L.A.Bromberger: None. S.R.Bruce: Consultant; Self; Dance Biopharm Holdings Inc., MannKind Corporation, Oramed Pharmaceuticals.
There were many presentations that looked incredibly interesting. You can look at the full calendar by clicking on the “Online Planner” link on the page below.