In the study of patients with type 1 diabetes, those treated with Afrezza had a mean 0.20–percentage point drop in HbA1c from baseline at 24 weeks, compared with a 0.42–percentage point drop among those on insulin aspart. In the study of patients with type 2 diabetes who were on metformin or at least two other oral diabetes drugs, those treated with Afrezza had a mean 0.84–percentage point drop in HbA1c from baseline, compared with 0.41 at 24 weeks in those on placebo. In trials, the most common adverse events were a dry, transient cough and transient changes in pulmonary function. Lung cancer rates were similar to what would be expected in the general population, according to the company. Hypoglycemia was slightly lower among those on Afrezza in both studies.
There have been four lung cancers in patients treated with Afrezza in clinical trials, including two cases in patients with no smoking history. Since the product delivers a high level of insulin to the lungs, and insulin may activate growth receptors in the lungs, the panel agreed this was a significant issue that should be followed in postmarketing studies. The company has proposed a prospective observational registry of patients to track the incidence of primary lung cancers, as well as other malignancies and serious pulmonary, allergic, and hypoglycemic events that require medical intervention. Labeling would recommend that spirometry be done every 6 months during treatment.
Voting for approval, panel chair Dr. Robert Smith, professor of medicine at Brown University, Providence, R.I., said that inhaled insulin "represents a drug that will serve some patients that are not effectively served by currently available forms of insulin." The data about the potentially serious adverse effects "were not strong enough that I feel it is imperative to resolve those questions" before marketing, he added, but stressed that these safety issues, including the potential for lung cancer and deteriorating lung function, are "very, very important to follow up."
The panelist who voted against approval for type 1diabetes, Dr. David Cooke, clinical director of the division of pediatric endocrinology at Johns Hopkins University, Baltimore, said he was concerned that the risks outweighed the benefits in this group of patients, particularly because of the potential increased risk of cancer. But he said he was more confident about the risk-benefit profile for patients with type 2 diabetes because they would not be exposed to the drug for as long as patients with type 1 diabetes, and that the inhaled insulin may provide some type 2 patients who might otherwise put off taking insulin with a more acceptable and effective option.
The FDA is expected to make a decision on approval by April 15. The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts. Occasionally, a panelist is given a waiver but not at this meeting.