Overview of Inhaled Insulin Products
After an extensive search, we found a list of inhaled insulin products that have been developed thus far: Exubera, AIR, Spiros, Technosphere, PROMAXX, Aerodose Insulin, and AERx Insulin. Technosphere was later renamed to Afreeza.
Because case studies for Exubera and Afreeza will be covered in a different Wonder request, the two companies will not be explained in full detail for this particular request.
Unfortunately, after extensive research, besides the product Afreeza, there are no other case studies of successful products nor current inhaled insulin products in development that are openly available to be found. Currently, Afreeza is the only inhaled insulin product that is FDA-approved and has not been discontinued. Its 4 biggest competitors, Exubera, AERx Insulin, Aerodose Insulin, and AIR have already been discontinued.
There is a lack of recent information publicly available for products Spiros and PROMAXX. This may be due to the fact that pharmaceutical companies may be guarding the development status of these products. PROMAXX completed phase I clinical studies in December 2005, and although additional clinical data was added in 2007, there haven't been any recent news on the status of its current development.
Under the company Alkermes, AIR, an inhaled insulin product using a dry powder form of insulin, was discontinued at Phase-III for Type-1 diabetes mellitus in 2008 after their funding partner, Eli Lilly, terminated the development and license agreement.
Case studies for AERx Insulin, which was discontinued after news of its competitor Exubera's failure, and Aerodose Insulin, which was discontinued due to lack of funding, were used as representatives of failed products and have been provided below.
FailED CASE STUDIES
CASE STUDY # 1: AERx Insulin Diabetes Management System
The AERx Insulin Diabetes Management System "delivers an aerosol of liquid insulin" into the lung. It features a unique system that only delivers the drug to the lung if the patient is breathing optimally and correctly. This is important since optimal breathing allows the insulin to be better deposited and absorbed by the lung. By using strips of liquid insulin, dosage can be adjusted to the nearest unit, similar to insulin injections. There is also a datadownloading and monitoring aspect that saves and monitors session data, allowing patients, physicans, and clinicians to review data on dose administration and breathing patterns, as well as information on patient compliance. Both type 1 and type 2 diabetes mellitus patients have been studied for this system.
To be more precise, the device was a "microprocessor-controlled inhaler" that monitored the patient's breathing patterns by actuating "when a combination of breathing parameters fell to a predetermined range." The insulin would move through a single-use nozzle that created a fine mist. In order to release the mist in a uniform manner, hundreds of 1 μm holes were contained in the nozzle.
"Compared with subcutaneous human insulin, the pharmacokinetic and pharmacodynamic profile of inhaled insulin with AERx iDMS is similar, but with a more rapid onset of action." Data from the studies demonstrated that using AERx iDMS is "as consistent and reproducible as subcutaneous human insulin." A study in 2007 concluded that, "no major safety concerns have been raised with respect to pulmonary function tests." In 2005, it was reported that according to the preliminary data at that time, patients transitioning from injections to AERx iDMS "showed higher compliance to therapy, demonstrated by improved glycemic control."
However, in 2008, "Novo Nordisk elected to discontinue further study with the AERxiDMS system given the experience of Pfizer with Exubera." Further information on the reasoning for discontinuing AERx iDMS couldn't be found, however it was evident that the failure of the competitor product Exubera affected the owners of AERx iDMS to the point of discontinuing the product.
CASE STUDY #2: Aerodose Insulin
Aerodose Insulin used a breath-activated inhaler to deliver liquid insulin. A cartridge was incorporated to be able to adjust the dosage based on insulin requirements.
RESEARCH STUDY: METHODS
The product was studied in a small group of 15 patients (nonsmokers, 10 men, aged 47-77 years) with type 2 diabetes mellitus. The patients received two 240-unit doses of INH via inhaler and another "two 24-unit doses of SC under euglycemic clamp conditions on four separate study days." Over the next 8 hours, glucose infusion rates (GIRs) and serum insulin concentrations were closely monitored.
RESEARCH STUDY: RESULTS
When comparing the related coefficients of variation (CV), there were "no significant differences between the treatments during 0-3 hours (19% for INH versus 23% for SC) or 0-8 hours (22% for INH versus 16% for SC)." The INH, which again, were delivered via inhaler, "exhibited a shorter peak insulin concentration" and "shorter time to peak metabolic effect" compared with SC (P < 0.001). It was also reported that "no adverse events were observed."
RESEARCH STUDY: CONCLUSIONS
The study concluded that the "comparable dosing reproductibility and shorter time to peak action" of the INH delivered via inhaler to the SC "suggest that INH delivered via the Aerodose Insulin Inhaler can provide reliable preprandial dosing of insulin in patients with type 2 diabetes."
Although Aerogen Corporation saw promising results, the company "failed to secure a financial partner and halted development of the product in January 2003."
After an extensive search, we found a list of inhaled insulin products that have been developed thus far: Exubera, AIR, Spiros, Technosphere, PROMAXX, Aerodose Insulin, and AERx Insulin. Technosphere was later renamed to Afreeza. However, some lacked any current information on their development, while others had already been discontinued. AERx Insulin, which was discontinued after news of its competitor Exubera's failure, and Aerodose Insulin, which was discontinued due to lack of funding, were used as case studies for failed inhaled insulin products. The only truly successful product was Afreeza as the only inhaled insulin product that is FDA-approved and has not been discontinued.