Assistant Managing Editor

It was just as MannKind Corp.'s bearish investors predicted when the FDA said it was extending the PDUFA date for inhaled insulin candidate Afrezza: The agency issued a complete response letter – the second – for use of the product in Type I and Type II diabetes.

While the first CRL did not specifically require additional clinical data – the agency instead asked for more information on Afrezza's clinical utility and the company's next-generation inhaler device – the second letter requested the firm to conduct two clinical studies using its newer inhaler, one testing the product in Type I diabetics and the other in Type II disease. And at least one of those studies should include a treatment group using the MedTone inhaler from previous trials for a head-to-head comparison. (See BioWorld Today, March 16, 2010.)

Shares of MannKind (NASDAQ:MNKD) fell 72 cents Wednesday to close at $9.11.

The good news is that the Valencia, Calif.-based firm already has started two trials testing the new device. AFFINITY 1 is enrolling Type I diabetes patients, while AFFINITY 2 is enrolling Type II diabetics. "We plan to meet with the agency as quickly as possible in order to be confident that these trials, with appropriate modifications to incorporate a comparison to the MedTone device, will suffice in addressing the agency's questions," Alfred Mann, chairman and CEO, said in a statement.

He stressed that the FDA was asking only for data to confirm the bridging and handling of the new device.

MannKind had hoped to gain approval of Afrezza last year, with plans to submit a supplemental application after completing trials with the next-generation inhaler. That newer inhaler could be key to market uptake of the product.

Inhaled insulin has remained a shaky proposition following Exubera, which gained approval only to be pulled from the market by Pfizer Inc. and Nektar Therapeutics Inc. after dismal sales. A bulky and inconvenient inhaler was partly to blame. (See BioWorld Today, April 10, 2008.)

MannKind has soldiered on, even as other competitors backed away from inhaled insulin programs.

Partners Novo Nordisk A/S and Aradigm Corp. and partners Alkermes Inc. and Eli Lilly and Co. both dropped their respective late-stage programs in the wake of Exubera's demise.

A new player, however, recently emerged. Dance Pharma partnered with Aerogen Ltd. last week to develop an inhaled insulin product using Aerogen's OnQ aerosol generator technology.

The timeline for MannKind resubmitting a new drug application for Afrezza was not immediately clear. But the delay is almost certain to further hold up any partnering discussions.

Fourth-quarter financial results have not yet been released, but MannKind ended the third quarter with about $98 million in cash.

In addition to the clinical data, the FDA's letter also requested more information, including usage, handling, shipment and storage of the inhaler, plus updated safety information for Afrezza.