Regulatory Affairs

FDA issues CRL to MannKind Afrezza NDA

Published 20 January 2011

The US Food & Drug Administration (FDA) has issued a complete response letter (CRL) to MannKind for its new drug application (NDA) for Afrezza (insulin human [rDNA origin]) inhalation powder to treat patients suffering from type 1 and type 2 diabetes for the control of hyperglycemia.

In its CRL, the FDA has showed its concern regarding the use of the in-vitro performance data and clinical pharmacology data to bridge MannKind's next generation inhaler to the Phase 3 trials conducted using its MedTone inhaler.

Additionally, the FDA has asked the company to conduct two clinical trials involving MannKind's next generation inhaler and MedTone inhaler evaluating patients with type 1 diabetes in one trial and for assessing patients with type 2 diabetes in the second trial with at least one trial including a treatment group using the MedTone inhaler in order to obtain a head-to-head comparison of the data for the two devices.

Further, the FDA has also requested additional information concerning the performance characteristics, usage, handling, shipment and storage of the next-generation device, an update of safety information related to Afrezza as well as information on proposed user training and changes to the proposed labeling of the device, blister pack, foil wrap and cartons.

MannKind chairman and CEO Alfred Mann said as they have already begun a series of studies of the next-generation device in patients with type 1 (Affinity 1) and type 2 (Affinity 2) diabetes.

"Consistent with the direction we received in the complete response letter, these trials are designed to focus on careful titration of insulin dose and include at least twelve weeks of stable dosing," Mann said.

"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 about patient use and robustness of the next-generation device."