51成人动漫

HYATTSVILLE, Md. -- An FDA advisory panel has voted in favor of approving a new inhaled insulin device, Afrezza, as a short-acting treatment to improve glycemic control in both type 1 and type 2 diabetes.

The Endocrinologic and Metabolic Drugs Advisory Committee voted 13-1 here Tuesday to support approval of the device to treat adult patients with type 1 diabetes, agreeing that the device manufacturer, MannKind, demonstrated adequate evidence of safety and efficacy. One panelist who left early did not vote.

The panel showed unanimous support (14-0) for approving the device to treat adult patients with type 2 diabetes, based on demonstrated safety and efficacy. The FDA is not obliged to go along with its advisory committees' recommendations but it usually does.

The one panelist who voted against recommending approval of the device for the treatment of type 1 diabetes said his concerns over pulmonary and lung cancer risks with Afrezza use outweighed the proof of benefit of the drug-device combination.

"My greatest concern is related to the cancer risk and I think the way I saw the data, the efficacy of this was not as good as [injectable] insulin," said , associate professor of pediatrics at Johns Hopkins University School of Medicine, adding that more preclinical data would reassure him against the cancer risk.

"The convenience and desirability of avoiding injections and ease of use and all the hurdles that injections impose upon diabetics," are, however, an "an unambiguous benefit," Cooke continued. He cited decreased hypoglycemia as another potential benefit of the device in type 1 diabetics.

He voted Yes to approve the device to treat type 2 diabetes because he felt the "exposure time is likely to be shorter, given the older age of the average type 2 diabetic," thereby lowering the risk for longer-term complications such as decreased pulmonary function and lung cancer.

Before voting, panelists discussed pulmonary safety, including bronchospasm and loss of pulmonary function over time, as well as lung cancer risks. There had been an apparent increase in lung cancer with an earlier Pfizer inhaled insulin (Exubera).

The committee also discussed the lower HbA1c reductions seen with the inhaled insulin compared with injected insulin in type 1 diabetes, including the impact of efficacy differences on the overall risk-benefit ratio and whether the product would benefit specific subgroups of patients, such as those who are afraid of needles, those who might need insulin between meals, and patients with visual impairments or manual dexterity issues.

The panel generally agreed that although better treatment options are needed for type 1 diabetes in terms of managing glycemia and HbA1c, the manufacturer demonstrated borderline efficacy for the use of Afrezza in type 1 diabetics, providing grounds for uncertainty in the broad application of the drug-device to all patients with type 1 diabetes.

Panel members also considered whether there is a specific clinical setting and patient subgroup most appropriate for inhaled insulin in type 2 diabetes. The panel consensus was that there is not, at this point, an adequate treat-to-target trial, which would be "helpful and important" regardless of Afrezza's approval, according to the summary given by panel chairman , of Brown University in Providence, R.I.

Panel patient representative Rebecca Killion echoed the support heard from all 17 speakers during the open public hearing by voting Yes to approve Afrezza for use in both types 1 and 2 diabetics.

"Diabetics dance with the devil every single day. Our lives are a series of peaks and valleys," Killion said during the panel discussion.

This is MannKind's third attempt to obtain approval for Afrezza as a short-acting treatment to improve glycemic control in both type 1 and type 2 diabetes.

The company's new drug application for the device was denied in 2011 for reasons including insufficient data on the latest "Gen2" version of the inhaler. The application also was rejected the previous year, with FDA requesting more clinical and labeling information.

MannKind has now submitted data from two new pivotal trials in type 1 and type 2 diabetes, respectively.

For the noninferiority study evaluating Afrezza in type 1 diabetes, the new Gen 2 Dreamboat inhaler was compared with an older-generation inhaler (MedTone) and injected insulin.

FDA staff scientists, in a prepared for the Tuesday meeting, raised concerns about possible inadequate dose titration in the type 1 diabetes study, stating, "it is not clear how to interpret the results of this noninferiority study."

The reviewers also noted that study dropouts because of cough and other pulmonary problems did not appear to have changed meaningfully since the previous submission.

Noninferiority was achieved for the new inhaler, with HbA1c levels decreasing by 0.21 percentage points, compared with a decrease of 0.40 points for the older inhaler.

However, compared with injected aspart insulin, a decrease in FEV₁ (forced expiratory volume in 1 second) was seen among patients using the new inhaler, and a higher rate of discontinuation because of cough was seen in the Dreamboat group.

The type 2 study compared the Afrezza insulin powder with Technosphere insulin powder, and found significantly greater decreases in HbA1c among patients using the Afrezza powder (-0.82 versus -0.42 percentage points, P<0.0001).

Mild and moderate hypoglycemia was more common in the Afrezza group, but fewer severe adverse events occurred. Cough was the most common side effect.

Comment