Exubera Case Study

How Exubera^TM was formulated?

Exubera^TM is a spray-dried amorphous powder insulin formulation that is designed to provide insulin to the human lung alveoli (Figure1). The amorphous powder is stable at ambient conditions and compromises of 60% insulin in a protected sugar based environment. (1)The packaging of insulin involves blisters that with recombinant insulin 1mg or 3mg in 5mg powder that is containing mannitol, glycine and sodium citrate. In general, every inhalation provides the body with approximately 3 and 9 U of subcutaneous insulin. (2)The spray drying technique generates consistent inhalable particle size of less than 5 m which in theory is the preferred size for an effective inhalation in order to reach the Alveoli. The vacuum of the inhalation machine allows for delivering aerosolised cloud particles from powder filled blisters, (figure2).

Figure2. Exubera^TM inhaled insulin delivery system.

Figure1. an illustration of the human lung and the Alveoli. (source: Lecture notes)

The administration process of the insulin dose involves a slow and deep inhalation upon pressing the air pump. The inhalation device is about 22.86 cm long. It has a base which allows for retaining insulin powder in addition to a spacer chamber above (Figure2). The clear chamber of the device allows the patients to know instantly once the inhalation process is completed. (2) It specifically designed to provide the lung alveoli with a sufficient dose of insulin without relying on the inspiratory flowrate of the patient. (3) The device operates when pulling the spacer into place and air compression is being produced which penetrates the insulin blisters. The powder then enters the chamber as an aerosol cloud ready for inhalation.

Why Exubera^TM Was formulated?

Diabetes is a chronic disease and patients need to administrate insulin to control their high blood glucose level. Delivering insulin through injection is a tough and painful process for lots of patients. Also, insulin injection can cause dosing inconsistency which can lead to hyperglycemia or hypoglycaemia which happens as a result of inappropriate injection site, depth and volume. Therefore, the demand for a new, innovative and non-invasive route for insulin administration is high and Exubera^TM has specifically designed to meet the need of these patients. Theoretically, Exubera^TM meant to make the process of insulin administration easier and eliminates the psychological barriers related to subcutaneous insulin delivery.

Clinical Trials

A study of 2500 adults patients with type 1 and 2 diabetes shows that the peak concentration of insulin have been achieved quicker with Exubera^TM at an average of 49 minutes but side effects like cough, shortness of breath, sore throat and dry mouth were identified.(2)(4)

Figure.3 Glucose infusion rate of SC and inhalation administration in patients.(10)

Despite Exubera^TM showing a higher patients acceptability to the subcutaneous route (6) (7)(8), the efficacy rate of this product is from 10% to 20%. This is because about 30% of the insulin stays in the inhalation device and not inhaled. Practically, only about 40% of the insulin powder reaches the alveolar region, however, about 25% to 30% of this is absorbed by the systemic circulation.(10)

Was Exubera a commercial success?

The estimated cost of launching Exubera^TM to the market is approximately $1.3billion. It was introduced to the UK in August 2006 and the product was anticipated to make a worldwide sales of $2billions but instead the estimated sells were about $12millions due to Pfizer s marketing strategy as well as the practical difficulties of the device. Additionally, in the UK the NICE guidance and labelling restrictions made the prescribing process of Exubera^TM nearly impossible which contributed to a poor selling rate.(11)

Why were the sales of Exubera^TM under expectations?

Numerous reasons contributed to the failure of Exubera^TM including the strict labelling and national strategies. The guidelines and labelling restrictions of NICE in the UK made it nearly impossible for the doctors to prescribe Exubera^TM to lots of patients due to its lack of data on the long term side effects of the product to patients lung. This is because there is a strong link between lung cancer and what an individual inhale as the lung is not designed to take in powder. Also, Pfizer did not implement the right marketing strategies and did not wait for the market to open up for the first inhaled insulin product that was introduced to the market. Similarly, the cost of Exubera^TM was too high as it cost about $188 for a one month of insulin supply. Equally, the inhalation device and dose administration was not so convenient for patients since about 30% of the insulin remained in the device and causes a temporary cough for the patients during administration which makes the administration process more irritating than the injection root. Furthermore, the poor selling of the product could also be related to the product couldn t replace the insulin injection in type 1 diabetes patients due to its poor delivery rate(10%-20%). This contradict with the purpose of the product invention which is eliminating the psychological barriers associated to subcutaneous insulin administration. So technically the product was not beneficial for type 1 diabetes patients. Although clinical trials showed patients satisfaction with Exubera^TM was great, it did not improve the glycaemic control in type 1 and 2 diabetes which contradicts its promotional claim of maintaining log-term glycaemic control .

Conclusion

Although Exubera^TM seemed to be scientifically a unique formulation which makes the insulin administration easier and less painful for patients it appeared to be withdrawn from the market mainly for economic reasons. This is because the annual anticipated sales for Exubera^TM was 2 billion but the estimated sales were only 12 million worldwide because of Pfizer s marketing strategies for the first inhaled insulin introduced to the market as well as high cost of the product. In addition practical difficulties, and the poor delivery rate of insulin to the body meant that patients with type1 diabetes could not use this product. Additionally, the lack of data of proving its promotional claim of maintaining log-term glycaemic control and the NICE strict labelling guidance meant that the clinicians could not recommend it to patients as often. All of these factors have contributed to a poor sales of Exubera^TM and therefore Pfizer had to withdraw the product from the market.