Understanding Technosphere Insulin

[itellthefuture777]

onlinelibrary.wiley.com/doi/abs/10.1111/1753-0407.13099?af=R

Understanding Inhaled Technosphere Insulin: Results of an Early Randomized Trial in Type 1 Diabetes Mellitus
Janet B. McGill Daniel Weiss Marshall Grant Marisa C. Jones David M. Kendall Byron J. Hoogwerf
First published: 31 July 2020

Background
Technosphere® Insulin (TI) is an inhaled insulin. Studies comparing TI with short‐acting insulin analogues provide important insights on efficacy, dosing, and time course of action.

Methods
Planned enrollment of 230 subjects was limited to 138 due to premature study discontinuation. The primary efficacy endpoint was a non‐inferiority of HbA1c of 0.4%. for TI compared with insulin lispro (LIS) in a 16‐week phase 3 randomized clinical trial in type 1 diabetes mellitus.

Results
Glycated hemoglobin values were similar in the TI and LIS groups at the beginning of the trial ( 7.8 and 7.6%, respectively) and at trial endpoint (7.7 and 7.6%, respectively). Least squares mean changes from baseline were similar between study groups. Glucose values after a standard meal were significantly lower with TI in the first 90 minutes post‐meal compared with LIS. Mild or moderate hypoglycemia event rates were also significantly lower with TI compared with LIS (5.97 vs 8.01, respectively; P =0.0269). Cough was the most commonly reported adverse event with TI. Pulmonary function as measured by forced expiratory volume in 1 second was not different between groups at baseline, 16 weeks or 4 weeks off study drug.

Conclusions
HbA1c was unchanged and overall glucose control was comparable between groups. Treatment with TI resulted in improved post‐meal glucose and a lower risk of hypoglycemia compared with LIS.

[mango]

This is some of the Veins of Gold Dr. Kendall was referring to


• Glucose values after a standard meal were significantly lower with TI in the first 90 minutes post‐meal compared with LIS.

• Mild or moderate hypoglycemia event rates were also significantly lower with TI compared with LIS (5.97 vs 8.01, respectively; P =0.0269).

• Pulmonary function as measured by forced expiratory volume in 1 second was not different between groups at baseline, 16 weeks or 4 weeks off study drug.

[mnkdfann]

Veins of gold they may be, but I'm not convinced this study / article will be much of a game changer.

Some comments / observations about the paper ... 

I wonder what 'personal reasons' people had for discontinuing use of TI?

"The ITT population included 61 subjects in the TI arm and 65 subjects in the LIS arm ... More subjects discontinued in TI group than in the LIS group (n=13 vs. 5, Supplementary Table 1). There were increased discontinuations due to respiratory TEAEs (n=4 vs. 0 in comparator) related to cough that resolved upon discontinuation of study drug. Additionally, more subjects discontinued the study in the TI arm due to withdrawal of consent or “other” (n=7 vs. 2), most often citing personal reasons."

Also:

"Cough was the most common side effect reported in the TI group with approximately 48% of participants reporting a cough at any point during study follow-up (Supplementary Table 3). Cough was described as intermittent and generally occurred within 10 minutes of dosing."

The article contains this interesting historical blurb ('rabbit unit', so cute):

"Some of the concern over the apparent difference in the unit-dose effect arises from confusion between the definition of an insulin unit, both in terms of clinical “effect” and unit “amount.” When insulin was first developed by extraction techniques, each batch was tested for clinical comparability and the unit of insulin (using the so-called “rabbit unit”) was defined as “the amount of insulin which is capable of lowering the blood sugar to the convulsive level within three hours, in rabbits of approximately 2 kg weight from which food has been withheld for 24 hours.” Note that the insulin in the biopotency test was administered by subcutaneous injection, binding the definition to this specific route of administration. As the preparations of insulin have become purer, the definition of a unit has also changed. Both the international and USP units of insulin are now defined in terms of amount (0.0347 mg insulin pure, or 6 nmol), and not by clinical effect. The relationship between amount and effect still generally holds for subcutaneous insulin, but this relationship does not necessarily hold when insulin is administered by other routes."

Also interesting (at least to me) that the authors are supported by nearly every Pharma under the sun (but I suppose that may be par for the course in medicine):

"JBM has received speaker fees from Aegerion, Dexcom, and Janssen; research funding from Dexcom, Medtronic, and Novo Nordisk; and served as a consultant or advisor for Aegerion, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, Metavant, Novo Nordisk, and Valeritas. DW has received speaker honoraria or clinical research funding from Eli Lilly, Janssen, Novo Nordisk, Sanofi-Aventis, and Gan Lee and has served on an advisory board for AstraZeneca. MG and MCJ are full-time employees of MannKind Corporation. DMK is a full-time employee of MannKind Corporation and a minor stockholder of Eli Lilly and Co. BJH is a consultant for MannKind Corporation and a minor stock older of Eli Lilly and Co."