Exubera, the first non-injectable insulin system approved by the Food and Drug Administration (FDA) in 2006, was designed to revolutionize diabetes care. Its purpose was to provide adult patients with Type 1 and Type 2 diabetes a needle-free alternative for managing hyperglycemia. The system utilized a specialized inhaler device to administer a powdered form of human insulin directly into the lungs via pulmonary inhalation. This offered a new option for the millions of people who relied on multiple daily injections to control their blood sugar.
The Promise of Inhaled Insulin
The concept of inhaled insulin held promise for patients by eliminating the psychological and practical barriers associated with daily subcutaneous injections, such as needle phobia. The mechanism relies on the lungs’ vast surface area and rich blood supply, allowing the dry insulin powder to be rapidly absorbed into the bloodstream. This delivery method created a profile similar to a rapid-acting insulin, with a quicker onset of action compared to traditional injected regular human insulin.
In clinical studies, Exubera achieved peak insulin concentration significantly faster than injected regular insulin (49 minutes versus 105 minutes). This pharmacokinetic advantage meant the insulin could better mimic the body’s natural mealtime surge, offering improved postprandial glucose control. Breathing in the dose before a meal represented an improvement in quality of life, potentially making insulin therapy more acceptable and improving adherence.
Health Concerns and Patient Experience
Despite its innovative delivery method, Exubera introduced several clinical and practical hurdles. A primary concern was the potential for long-term pulmonary effects, necessitating mandatory pulmonary function testing (PFTs) for all patients. The FDA recommended patients undergo spirometry tests before starting Exubera and periodically thereafter, typically every six months, to monitor for any decline in lung function.
This requirement was a barrier for both patients and physicians, adding complexity and cost to the treatment regimen. Dosing was also complex and confusing for users accustomed to traditional insulin units. Exubera was dosed in milligrams (1 mg and 3 mg blisters), which did not translate simply to standard international units (IU) of injected insulin. For instance, three 1 mg blisters did not provide the same systemic exposure as one 3 mg blister, complicating dose conversions and adjustments.
The design of the inhaler device added to the practical difficulties. The unit was large and bulky, often described as resembling a can of soda or a flashlight when folded. This lack of portability and discretion made it inconvenient for patients who needed to administer insulin several times a day, contrasting sharply with the small, discreet insulin pens popular at the time.
The Market Failure and Discontinuation
The combination of practical drawbacks and market dynamics led to a swift commercial failure. Despite Pfizer’s investment and marketing efforts, Exubera failed to gain acceptance among patients and physicians. Sales were poor, falling far short of the projected $2 billion annual revenue Pfizer had anticipated.
In the first nine months of 2007, Exubera generated only $12 million in worldwide sales. The low sales figures, compounded by high manufacturing and marketing costs, prompted Pfizer to withdraw the product. In October 2007, less than two years after its launch, the company officially removed Exubera from the market.
This discontinuation was attributed to commercial viability rather than safety concerns, resulting in a $2.8 billion pre-tax write-off for Pfizer. The lack of physician buy-in, particularly due to the mandatory lung function testing and the confusing dosing system, proved insurmountable. Ultimately, the system’s cost and inconvenience outweighed the benefit of avoiding an injection, leading to its removal.
Exubera’s Legacy and Modern Successors
The commercial failure of Exubera created caution across the pharmaceutical industry regarding subsequent inhaled insulin products. It provided a lesson that innovation in drug delivery must be coupled with superior device design, simple usability, and a compelling cost-benefit ratio to ensure patient compliance. The need for long-term safety data, particularly concerning lung function, was also emphasized by the regulatory requirements placed on the product.
The current FDA-approved successor to Exubera is Afrezza, approved in 2014, which learned from many of its predecessor’s flaws. Afrezza features a smaller and more discreet inhaler, addressing the bulkiness issue that plagued Exubera. Its dosing is also simplified, using unit increments that are easier for patients and prescribers to manage than Exubera’s milligram-based blisters. Exubera’s run underscored that for a novel drug delivery system to succeed, it must not only be clinically effective but also seamlessly integrate into the daily lives of patients.