Exubera (recombinant human insulin inhalational) / Nektar Therapeutics - LARVOL DELTA

Pulmonary Safety and Clinical Considerations for Inhaled Insulin: A Comprehensive Review. (PubMed, Diabetes Technol Ther) - "Ongoing innovation in inhaled insulin led to FDA approval of Technosphere® Insulin (TI), the therapeutic component of the Afrezza® inhaled insulin delivery system (MannKind Corporation, Westlake Village, CA). However, many clinicians remain cautious about the potential for adverse events with chronic use beyond the duration of closely monitored clinical trials. In this article, we address the pulmonary safety concerns that are often associated with TI and present evidence demonstrating the safety of TI in type 1 diabetes and type 2 diabetes populations."

Journal • Review • Cough • Diabetes • Metabolic Disorders • Respiratory Diseases • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

"Exubera is such a great name to be wasted on such a shitty product" (@whatprobability)

Celebrating A Century Of Insulin Discovery: A Critical Appraisal Of The Emerging Alternative Insulin Delivery Systems. (PubMed, Curr Drug Deliv) - "These efforts have not been without victory, as we have seen the emergence of pulmonary (Exubera and Afrezza) and buccal insulin delivery systems licenced for therapeutic use...However, at present, there are no clinical studies that have reported the efficacy of transdermal insulin administration With technological advancement, there is a potential to develop yet another insulin delivery system which would likely enter the markets. Although these novel delivery systems are welcome, however, emerging competing products should be welcome and appreciated."

Journal • Diabetes • Hypoglycemia • Immunology • Inflammation • Metabolic Disorders • Type 1 Diabetes Mellitus

Efficacy and Safety of Inhaled Human Insulin (Exu hera) Compared to Subcutaneous Insulin in Children Ages 6 to 11 Years with Type 1 Diabetes Mellitus: Results of a 3-Month, Randomized, Parallel Trial. (PubMed, J Pediatr Endocrinol Metab) - "The efficacy and safety profiles shown in this study are the foundation for further investigation of EXU in this population."

Clinical • Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Pediatrics • Respiratory Diseases • Type 1 Diabetes Mellitus

Inspiration and Exasperation: The Challenges of Inhaled Biologics. (PubMed, Toxicol Pathol) - "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). As a result, scientific knowledge within the toxicologic pathology community is fragmented with precious little publicly available data. Therefore, one of the aims of this special edition was to generate a collection of manuscripts that pathologists and toxicologists could refer in order to understand the pathology, mechanisms of toxicity, immunogenicity, and challenges associated with the development of inhaled biotherapeutics."

Journal

"not only into the lungs, but deep into the lungs - did Exubera/Afrezza reach the alveoles?" (@tomorrowdaworld)

Pulmonary and cardiovascular safety of inhaled insulin in routine practice: The Exubera Large Simple Trial (VOLUME). (PubMed, Contemp Clin Trials Commun) - P4 | "Clinically important declines in lung function that persisted more than 60 days were uncommon and of similar frequency in Exubera and usual care. NCT00359801."

Clinical • Journal

Oral insulin to remain a pin prick for pharma cos' research (Moneycontrol) - Biocon's molecule failed in P3 trials, putting paid to a decade of studies; There has been some progress in other modes of insulin delivery, from insulin inhalers to insulin patches from Roche & Calibra which have progressed to clinical trials; But scientists believe that demands for comprehensive data from drug regulators might delay the entry of such products in the markets, especially, after Pfizer's inhaled insulin Exubera had to be withdrawn after it led to lung problems

Therapy update • Diabetes

Lung Cancer-Related Mortality With Inhaled Insulin or a Comparator: Follow-up Study of Patients Enrolled in Exubera-Controlled Clinical Trials (FUSE) Final Results. (PubMed, Diabetes Care) - "These data cannot exclude an increased risk of lung cancer-related mortality associated with EXU use. If real, the absolute increased risk of lung cancer-related mortality was small (0.48 cases per 1,000 PY). For all-cause mortality-the most reliably measured end point with the clearest interpretation-EXU users did not experience an excess all-cause death rate (relative nor absolute) compared with users of other diabetes treatments over the study period."

Clinical • Journal

Mechanism of Action of Inhaled Insulin on Whole Body Glucose Metabolism in Subjects with Type 2 Diabetes Mellitus. (PubMed, Int J Mol Sci) - "There were no episodes of hypoglycemia and no change in pulmonary function at EOS. After 16-weeks of inhaled insulin Exubera® we observed a marked improvement in glycemic control by decreasing HGP and 24-h PG profile, and decreased FFA and triglyceride concentrations."

Clinical • Journal

Speaker (IDF 2019) - "Newer injectables like glargine 300 U/ml and degludec are ultra long-acting insulins which reduced the number of pricks and had good glycemic control with less hypoglycemia...Exubera was first rapid-acting inhaled insulin in the market, but it was withdrawn in 2007 due to fewer acceptances by physicians and patients. Newer inhaled insulin Afrezza based on a technosphere platform contains recombinant human insulin administered via a small thumb-sized device introduced in 2014 with modification in the size of the device...Other different ways of administration of insulin which can bypass hepatic first-pass metabolism are in a different phase of trial like buccal insulin, nasal insulin, ocular insulin; rectal insulin (bypasses the more proximal areas that are actively involved indigestion)...The preclinical study result has shown that SOMA has released the same plasma level of insulin compare to subcutaneous millipost administration. Learning Objectives History and..."

AFREZZA-INDUCED PULMONARY INFILTRATE (CHEST 2019) - "As a new innovation milestone in diabetes, inhaled insulin therapy was introduced as Exubera in 2006 and Afrezza in 2014. To the best of our knowledge, this is the first known case of pulmonary infiltrate secondary to Afrezza, that resolved after discontinuing the therapy. Larger studies are required for standardizing the administration and surveillance strategies for Afrezza, so that it may serve as a model for channeling other parenteral medications in future."

Spray-Dried PulmoSphere™ Formulations for Inhalation Comprising Crystalline Drug Particles. (PubMed, AAPS PharmSciTech) - "...These include inhaled proteins for systemic action (e.g., Exubera®) and high-dose inhaled antibiotics (e.g., TOBI® Podhaler™)...The formulations extend the range of doses that can be delivered with a portable inhaler from about 100 ng to 100 mg. The spray-dried particles exhibit significant advantages in terms of lung targeting and dose consistency relative to conventional lactose blends, while still maintaining the crystallinity of drug(s) in the formulated drug product."

Journal • Review