MannKind Corporation (Nasdaq: MNKD) announced that it has received a complete response letter from the U.S. Food & Drug Administration (FDA) regarding the New Drug Application (NDA) for AFREZZA® (insulin human [rDNA origin]) Inhalation Powder for the treatment of adult patients with type 1 and type 2 diabetes for the control of hyperglycemia.
A complete response letter is issued by the FDA's Center for Drug Evaluation and Research when the review of a file is completed and questions remain that preclude the approval of the NDA in its current form.
The principal issue raised by the FDA concerned the usage of 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. The FDA has requested that MannKind conduct two clinical trials with the next-generation inhaler (one in patients with type 1 diabetes and one in patients with type 2 diabetes), 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. In the complete response letter, the FDA stated that after an adequate titration of study medication there should be at least twelve weeks of relatively stable insulin dosing at the end of the treatment period.
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.
"As we reported last fall, we 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," said Alfred Mann, Chairman and Chief Executive Officer of MannKind Corporation. "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. 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."
Mr. Mann continued, "While we are disappointed with the complete response letter, we are encouraged that the FDA is asking for clinical studies only to confirm the bridging and handling of the next-generation device in order to compare it to the device used in our extensive clinical program. We remain committed to working with the FDA to make AFREZZA available to people with diabetes."
About AFREZZA®
AFREZZA® is a novel, ultra rapid acting mealtime insulin therapy being developed by MannKind Corporation for the treatment of adult patients with type 1 and type 2 diabetes for the control of hyperglycemia. It is a drug-device combination product, consisting of AFREZZA Inhalation Powder pre-metered into single use dose cartridges and the light, discreet and easy- to-use AFREZZA Inhaler. Administered at the start of a meal, AFREZZA dissolves immediately upon inhalation and delivers insulin quickly to the blood stream. Peak insulin levels are achieved within 12 to 14 minutes of administration, mimicking the release of mealtime insulin observed in healthy individuals. To date, the AFREZZA clinical program has involved more than 50 different studies and over 5,000 adult patients with both type 1 and type 2 diabetes.