Indevus Pharmaceuticals, Inc. announced that based on a recent discussion with the US Food and Drug Administration (FDA) regarding the NDA filing for Nebido, the company expects the FDA to formally request that the company provide additional safety data prior to approving Nebido.
The company currently believes that an additional study will be required in order to supply the necessary data. The company expects to re-file for approval of Nebido in approximately 18 months followed by a 6 month FDA review. The company will finalize the requirements and initiate the study following the receipt of formal communication from the FDA which the company expects to receive by the original June 27, 2008 PDUFA date.
The company believes the requirement for additional data relates to a reaction immediately following the injection and is a known rare complication of oil-based depot injections. The reaction is believed to be the result of a small amount of the oily solution immediately entering the vascular system from the injection site and may be due to improper injection technique. The phenomenon is characterized by short-term reactions involving an urge to cough, coughing episodes or a shortness of breath. In rare cases the reaction has been classified as serious or the patient experiences other symptoms such as dizziness, flushing or fainting.
The company believes that the FDA's safety concern is derived from spontaneous post-marketing adverse event reports of the Nebido 1000 mg (4ml) dose. In the Indevus US clinical trials, which included a total of approximately 500 patients, there was a single, non-serious, instance of this phenomenon with the 750 mg (3ml) dosage of Nebido.
The patient did not require medical intervention and the event resolved without issue within 10 minutes. This patient has continued to receive regular injections without further incident. Because estimations of the true frequency of these events are difficult to determine from post-marketing reports on patients having received the 1000 mg (4ml) Nebido dose, FDA has asked for new data to more precisely calculate the incidence of the occurrence prospectively, as well as methods or procedures to mitigate the incidence with the 750 mg (3ml) dosage.
Glenn L. Cooper, MD, chairman and chief executive officer of Indevus stated, "We are very surprised and disappointed by the position the FDA is taking regarding the safety profile of Nebido given the large European experience. Rare coughing reactions have been well-described in the European product labeling of Nebido. We believe the information available on these cases indicates these reactions resolved without consequences and that our proposed labeling for Nebido in the US adequately addressed this issue. We intend to vigorously pursue the approval of Nebido and will allocate the resources necessary to conduct an additional study to satisfy the concerns of the FDA. From our verbal discussion with the FDA, we are not aware of any other approvability issues".
Dr Cooper continued, "Despite this disappointment we remain committed to our strategic direction. Vantas and Supprelin LA are both growing franchises that we will devote additional effort to promoting and we intend to extend our Sanctura XR sales force co-promotion agreement with Allergan by the full six months available to us. In addition, this summer we anticipate receiving approval to launch Valstar for bladder cancer and intend to initiate the -phase III clinical programme for our octreotide implant with an anticipated 2010 launch date for acromegaly. We will also continue to aggressively pursue business development opportunities".