Afrezza

Computer Modeling and Simulation (CM&S) provides the opportunity to drastically reduce clinical trial patient burden and advance regulatory decision making. At the suggestion of the US Food and Drug Administration (FDA), MannKind Corporation and Nudge BG submitted an application to the FDA Model-Informed Drug Development (MIDD) pilot program to support a label change for the initial dose of Afrezza® (insulin human), a novel inhalable insulin with a rapid pharmacokinetic and pharmacodynamic profile. The MIDD pilot program demonstrates the FDA's commitment to advancing regulatory science through the adoption of evidence generated by CM&S...

Since the discovery of insulin, continuous developments of this peptide have led to better management of diabetes mellitus, thus leading to a decrease in diabetes-related mortality. Despite these developments, we have seen an increase in diabetes cases, which has further necessitated for more innovative methods of diabetes management. The subcutaneous administration of insulin remains the mainstay therapy for type 1 diabetes mellitus. However, despite the availability of insulin analogues with improved pharmacokinetics, challenges with the conventional administration exists...

The delivery of biotherapeutic molecules (antibodies, proteins, peptides) and nucleic acids via the respiratory route has presented challenges for regulatory approval, due in part to a lack of understanding of the expected pathology, mechanisms of toxicity, and immunogenicity induced by the inhalation route. Although the first inhaled biotherapeutic was approved some time ago (Dornase Alfa, Pulmozyme; Genetech, 1993), no other inhaled biotherapeutics have been marketed for the treatment of human disease other than the inhaled insulins (Exubera; Pfizer, 2006 and Afrezza; Mannkind Corporation, 2014)...

BACKGROUND AND OBJECTIVE: Technosphere® Insulin (TI), a human insulin powder for inhalation (Afrezza® ; MannKind Corporation, Westlake Village, CA, USA), is an ultra-rapid-acting inhaled insulin indicated to improve postprandial glycemic control in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Because TI is absorbed across the alveolar membrane, the objective of this analysis was to characterize its pulmonary safety. METHODS: Pooled data from 13 phase 2/3 clinical studies in 5505 patients with T1DM or T2DM treated with TI, Technosphere inhalation powder without insulin (TP; placebo), or active-comparator treatment were analyzed for incidences of respiratory treatment-emergent adverse events (TEAEs), changes in pulmonary function, and lung malignancies...

OBJECTIVE: A major obstacle in optimizing the performance of closed-loop automated insulin delivery systems has been the delay in insulin absorption and action that results from the subcutaneous (SC) route of insulin delivery leading to exaggerated postmeal hyperglycemic excursions. We aimed to investigate the effect of Afrezza inhaled insulin with ultrafast-in and -out action profile on improving postprandial blood glucose control during hybrid closed-loop (HCL) treatment in young adults with type 1 diabetes...

A novel pure insulin spray-dried powder for DPI product (Ins_SD) was studied with respect to physico-chemical stability, in vitro respirability, bioavailability, activity and tolerability. Ins_SD powder exhibited a very high in vitro respirability, independently of the DPI product preparation (manual or semi-automatic). Physico-chemical characteristics of Ins_SD powder remained within the pharmacopoeia limits during 6 months of storage at room temperature. PK/PD profiles were measured in rats that received the pulmonary powders by intratracheal insufflation and compared with Afrezza inhalation insulin...

BACKGROUND: Diabetes is one of the most common chronic metabolic disorders which affect the quality of human life worldwide. As per the WHO report, between 1980 to 2014, the number of diabetes patients increases from 108 million to 422 million, with a global prevalence rate of 8.5% per year. Diabetes is the prime reason behind various other diseases like kidney failure, stroke, heart disorders, glaucoma, etc. It is recognized as the seventh leading cause of death throughout the world...

At present, the main form of insulin administration is the invasive subcutaneous (s.c.) route and, for many patients, this means managing their glucose levels with multiple daily injections, which is both painful and difficult to administer chronically. To increase patient compliance, products are slowly reaching the market that are more patient friendly, such as the insulin patch-pump systems, including Omnipod and V-Go, but also the inhaled-insulin Afrezza® and the buccal insulin Oral-lyn™. In this review, we outline the history of insulin, the various options that are currently available in practice for insulin delivery, and the non-invasive delivery systems that have entered the different stages of clinical trials over the past decade...

Treatment with Afrezza® (insulin human) inhalation powder in individuals with type 1 diabetes (T1D) reduces HbA1c levels similar to rapid-acting insulin analogs, but with significantly less hypoglycemia due to its unique time action profile. Examinations of studies of Afrezza pharmacokinetics/pharmacodynamics, relevant clinical trials, and U.S. Food and Drug Administration (FDA) documentation suggest that current FDA-mandated dosing recommendations for initiating Afrezza treatment may not result in optimal glycemic control for individuals with T1D...

Oral inhalation offers the opportunity of targeting drugs locally to different regions of the respiratory tract or alternatively, using the high surface area of the alveoli for systemic delivery. Pulmozyme and the inhaled insulins (i.e. Exubera and Afrezza) are examples of the scope of pulmonary drug delivery of biopharmaceuticals-albeit with strikingly different commercial success. Particularly, the failure of Exubera and the subsequent overreactions (e.g. the unsubstantiated lung cancer fear), lastingly stunned the field of systemically inhaled protein and peptide drugs...

Diabetes Mellitus (DM) is a metabolic disorder characterized by relative or absolute deficiency of insulin, resulting in hyperglycemia. Subcutaneous insulin and Oral Hypoglycaemic Agents (OHA) constitute the main treatment option for DM. Insulin is administered by injection or continuous infusion to control glucose levels mainly in Type I diabetes. Newer routes both oral and non oral, for insulin administration are current direction of insulin research as insulin injection therapy is burdensome and painful for many patients...

Considerable progress in treatment of diabetes has been made in the nearly 100 years following the discovery of insulin, and advances in insulin therapy have improved convenience, quality of life, overall glycemic control (A1C), and risk of hypoglycemia. An unmet need remains for a mealtime insulin that can faithfully reproduce the metabolic profile that ensues following meal ingestion in healthy persons. A number of "ultra-fast" insulin programs have been initiated, and Afrezza® (insulin human; Inhalation Powder, MannKind Corporation, Danbury, CT) stands as the first such product to be approved by the US FDA...

Technosphere insulin (TI), Afrezza, is a powder form of short-acting regular insulin taken by oral inhalation with meals. Action of TI peaks after approximately 40-60 min and lasts for 2-3 h. TI is slightly less effective than subcutaneous insulin aspart, with mean hemoglobin A1c (HbA1c) reduction of 0.21% and 0.4%, respectively. When compared with technosphere inhaled placebo, the decrease in HbA1c levels was 0.8% and 0.4% with TI and placebo, respectively. Compared with insulin aspart, TI is associated with lower risk of late post-prandial hypoglycemia and weight gain...

BACKGROUND: Technoshere insulin (TI), Afrezza, is a form of short-acting human insulin taken by oral inhalation with meals. METHODS: literature search (English, French, Spanish) of all human studies and pertinent animal and in-vitro studies related to technosphere insulin until September 2016 with special emphasis on its safety. RESULTS: Compared to subcutaneous insulin aspart, TI is slightly less effective, the difference in hemoglobin A1c (HbA1c) reduction being 0...

UNLABELLED: Glycemic control is fundamental to the management of diabetes. However, studies suggest that a significant proportion of people with diabetes, particularly those using insulin, are not achieving glycemic targets. The reasons for this are likely to be multifactorial. The real and perceived risk of hypoglycemia and the need for multiple daily injections are widely recognized as key barriers to effective insulin therapy. Therefore, there is a clear unmet need for a treatment option which can help mitigate these barriers...

BACKGROUND: Technosphere(®) insulin (TI), an inhaled human insulin with a fast onset of action, provides a novel option for the control of prandial glucose. We used the University of Virginia (UVA)/Padova simulator to explore in-silico the potential benefit of different dosing regimens on postprandial glucose (PPG) control to support the design of further clinical trials. Tested dosing regimens included at-meal or postmeal dosing, or dosing before and after a meal (split dosing). METHODS: Various dosing regimens of TI were compared among one another and to insulin lispro in 100 virtual type-1 patients...

No abstract text is available yet for this article.

Afrezza (insulin human) inhalation powder: a new inhaled insulin for the management of type-1 or type-2 diabetes mellitus.

Afrezza® (insulin human) inhalation powder is a rapid-acting Technosphere® insulin (TI) administered via a breath-powered oral inhaler to patients with diabetes requiring prandial insulin. TI, a dry powdered formulation of recombinant human insulin adsorbed onto a proprietary carrier, is designed to deliver insulin to the deep lung, at the level of the alveoli, where it is absorbed into the systemic circulation. In a randomized, open-label, multinational, phase III trial (trial 171) in type 1 diabetes (T1DM) patients, prandial TI via the Gen2 inhaler provided noninferior glycated haemoglobin (HbA1c) lowering compared with prandial subcutaneous insulin aspart...

The current review was designed to compare between the insulin inhalation systems Exubera and Afrezza and to investigate the reasons why Exubera was unsuccessful, when Afrezza maker is expecting their product to be felicitous. In January 2006, Pfizer secured FDA and EC approval for the first of its kind, regular insulin through Exubera inhaler device for the management of types 1 and 2 diabetes mellitus (DM) in adults. The product was no longer available to the market after less than two years from its approval triggering a setback for competitive new inhalable insulins that were already in various clinical development phases...