Telecon - Cervarix, October 18, 2007

DATE: 18 October 2007
SUBJECT: Cervarix BLA submission
CBER Representative: Norman W. Baylor, Ph.D.
GSK Representative: Dr. Vincent Ahonkai

I called Dr. Vincent Ahonkai this morning to notify him that the VRBPAC tentatively scheduled for December 12, 2007 to discuss the Cervarix BLA would be cancelled, and rescheduled for a future date. I explained to Dr. Ahonkai that we need to complete our analysis of the neuroinflammatory events reported in the BLA before we can reach any conclusions on the safety of Cervarix. Further, there are still narratives on subjects that we requested in September for which we are waiting to receive from GSK. I told Dr. Ahonkai that I appreciated GSK’s efforts in responding to our requests and acknowledged that we understood the magnitude of the effort on GSK’s part to provide these data to us.

Dr. Ahonkai responded that GSK had communicated recently with Ms. Christine Walsh about the December VRBPAC, and after speaking with her, GSK had communicated to some of their stakeholders that they would be taking Cervarix to the VRBPAC in December 2007. I reminded Dr. Ahonkai of our conversation a couple of months ago where I told him that until we assess all of the data in the BLA and reach a conclusion on the MPL issue, the December date for the VRBPAC is tentative. Dr. Ahonkai stated that he understood. I asked Dr. Ahonkai whether GSK had completed an in-depth analysis of their data, the neuroinflammatory events in particular. Dr. Ahonkai stated that GSK has conducted an in-depth analysis of the data across all of their MPL-containing products and consulted with experts within and outside of GSK. Further, their Data Safety Monitoring Committee, who is not blinded to the data, concluded that there were no imbalances in the events reported between the vaccine and control groups. I asked Dr. Ahonkai whether GSK had done an in-depth analysis of the neuroinflammatory cases reported, and he stated that GSK had not, and had not planned to do so. I strongly recommended to Dr. Ahonkai that GSK conduct such an analysis and consult their experts specifically about these cases. I proposed to Dr. Ahonkai that once we complete our analysis and GSK has conducted and completed an independent analysis of these events, we should meet and discuss our conclusions prior to going forward with a VRBPAC. Dr. Ahonkai agreed.

Dr. Ahonkai asked would GSK be receiving an official correspondence that the December 12, 2007 VRBPAC would be cancelled or would this telecom serve that purpose. I responded that this telecom would serve that purpose. Dr. Ahonkai asked when would GSK be receiving correspondence from FDA outlining all of the deficiencies in the Cervarix BLA. I responded that we would be issuing a CR letter outlining the deficiencies in the BLA by the action due date; however, we would try to issue this letter in advance of the action due date. Dr. Ahonkai asked whether I could give him a timeframe as to when GSK would be receiving the CR letter. I responded that I could not. Dr. Ahonkai asked how would the action due date be affected by the cancellation of the December VRBPAC. I reminded Dr. Ahonkai that the CR letter will stop the clock, and the clock would not be restarted until after we received a complete response from GSK to our CR letter, and the clock would be extended 6 months. I told him that this does not mean that we would take 6 months to complete our review of the additional data. I reiterated that we will work with GSK to move this application forward, but it will be critical for FDA and GSK to analyze all of the available data before presenting this application to the VRBPAC. I also reminded him that there may be other deficiencies beyond the assessment of MPL, and these, of course, would also be communicated in the CR letter. Dr. Ahonkai stated that he would communicate our decision to cancel the VRBPAC to his upper management within GSK, and would be back in communication with me afterwards. I told him that would be fine. I further stated that that FDA’s review team for Cervarix would communicate directly with GSK’s Cervarix team to discuss next steps.
