VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE
September 9, 2009
Hilton Hotel, Gaithersburg, MD
Dr. John Modlin, Chair ##
Dr. Lisa Jackson #
Dr. Jack Stapleton #
Dr. Vicky Debold *
Dr. Jose Romero #
Dr. Pablo Sanchez
Dr. Frank DeStefano
Dr. Peter Gilbert
Dr. Margaret Rennels **#
Dr. Norman Baylor
Dr. Robin Levis
Dr. Wellington Sun
Dr. Nancy Miller
Dr. Jeffrey Roberts
Temporary Voting Members
Dr. Michael Greene +
Dr. Lauri Markowitz
Dr. Kenneth Noller
Dr. Pamela McInnes
Dr. Melinda Wharton
Dr. Bruce Gellin
Dr. Lisa Rider ++
Dr. Robert Seder ++
Dr. Theodore Tsai +++
Dr. Elizabeth Unger
Dr. Barbara Howe, GSK
Dr. Martine Wettendorf, GSK
Dr. Gary Dubin, GSK
Dr. Thomas Verstraeten, GSK
Dr. Dalya Guris, Merck & Co.
Dr. Patrick Brill-Edwards, Merck & Co.
Designated Federal Official
Christine Walsh, R.N.
Committee Management Specialist
These summary minutes for the September 9, 2009 Meeting of the Vaccines and Related Biological products Advisory Committee were approved on April 11, 2011.
I certify that I participated in the September 9, 2009 Meeting of the Vaccines and Related Biological Products Advisory Committee and that these minutes accurately reflect what transpired.
Christine Walsh, R.N.
Designated Federal Official
John Modlin, M.D.
Chair (Topic 1)
Michael Greene, M.D.
Acting Chair (Topic 2)
|* Consumer Representative|
+ Acting Chair Topic 2
|## Did Not Attend Topic 2|
# Did Not Attend
++ Attended Topic 1 only
|+++ Acting Industry Rep|
The Chair, Dr. John Modlin called the Meeting of the Vaccines and Related Biological Products Advisory Committee to order at 8:00 a.m. ET on September 9, 2009. The committee discussed the safety and effectiveness of Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant, in females and the safety and effectiveness of vaccinating males with Gardasil, (Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine).
An Open Public Hearing was announced for each topic. Several public comments were made.
Following is a summary of the discussion. Additional information and specific details may be obtained from the transcript of the meeting. The transcript may be viewed on the FDA website.
Proceedings were adjourned at approximately 5:00 p.m. ET on September 9, 2009.
After opening administrative remarks, Dr. Robin Levis, FDA introduced the first topic; Safety and Effectiveness of Human Papillomavirus Bivalent (Types 16 and 18) Vaccine Recombinant, in females and presented the committee with the questions. Following Dr. Levis, the product sponsor, GlaxoSmithKline presented. Presentation content by the company included vaccine design, efficacy, safety, a pharmacovigilence plan, and a benefit/risk conclusion. Following GSK, Dr. Nancy Miller made presentation with topics that included product proposed indication, efficacy, immunogenicity, safety, and post-marketing studies.
The committee voted favorably in response to the following questions:
1a. Do the data support the efficacy of Cervarix for the prevention of HPV 16/18 related cervical cancer, CIN2+, AIS, and CIN1+ in females 15-25 years of age? (12 yes, 1 no, 0 abstain)
There was discussion regarding the data presented and demonstration of efficacy in prevention of cervical intraepithelial neoplasia (CIN2+) as well as AIS and CIN. CIN2+ included CIN2, CIN3, AIS and invasive cervical cancer. This was a composite endpoint. After discussion, the majority of the committee voted in the affirmative. .
1.b.Do the immunogenicity bridging data support effectiveness for prevention of HPV 16/18 related cervical cancer, CIN2+, AIS, CIN1+ in adolescent females 10-14 years of age? (12 yes, 1 no, 0 abstain)
In summary, based on the immunogenicity of the vaccine, the biological plausibility, the natural history of HPV infection in humans, as well as the precedent that the currently licensed vaccine was also licensed for use in younger females based on bridging immunogenicity data, the committee was of the opinion that bridging data supports effectiveness of the vaccine in females 10-14 years of age.
- Please comment on the strength of the data to support the efficacy of Cervarix for the
prevention of any non-vaccine HPV related CIN2+ in females 10-25 years of age.
The committee believed that there is basis for indicating that the bivalent vaccine does protect against some non-vaccine HPV serotypes, most likely those to which there has been demonstrated cross-protection in animal models or cross-neutralization. However, there was a difference of opinion among committee members as to whether or not a specific non-vaccine HPV type, i.e. HPV-31, should be individually included. (No vote was taken on this comment.)
- Do the safety data support the safety of Cervarix for use in females 10-25 years of age? (11 yes, 1 no, 0 abstain)
- Please comment on imbalance noted in spontaneous abortions.
The expected rate of spontaneous abortions in the general population was discussed, and was reported to be higher than the rate observed in the clinical trials presented for either the vaccine or control group. The sponsor reported that they had begun a pregnancy registry in the United Kingdom one year ago, which will continue. In addition, a pregnancy registry is planned for the United States. Further, the sponsor is planning a Phase 4 study to study this issue after licensure.
- Please comment on findings for neuroinflammatory events and diseases of potential autoimmune etiology.
The committee in general advised that a post-marketing study be conducted to study these events.
- Please comment on other recommendations for post-marketing commitments.
The committee in general advised that there would be a need for a robust post-marketing surveillance phase IV study, particularly for the autoimmune conditions.
For the afternoon session, Effectiveness of Vaccinating Males with Gardasil, (Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine), Merck and CBER both gave presentations that included background information on HPV-associated anogenital disease in males and description of and analyses from the pivotal (020) and supportive (016 and 018) studies of Gardasil in males.
The committee discussed efficacy data with regard to the prevention of genital warts in males. High point estimates of efficacy and statistical significance, as defined by a 95% Confidence Interval above 0, were noted for the prevention of genital warts across several analysis populations and when including disease due to vaccine and non-vaccine HPV types.
After presentation and discussion, the committee voted favorably in response to the following questions:
The safety of Gardasil in males 9-26 years of age was presented and discussed. The status of ongoing international postmarketing safety surveillance in males was also discussed.
The committee voted favorably in response to both of the following questions:
- Do the efficacy data submitted to the BLA supplement support the use of Gardasil in males 9 to 26 years of age for the indication of prevention of genital warts?(7 yes, 0 no, 1 abstain)
- Do the data submitted to the BLA supplement support the safety of Gardasil for use in males 9 to 26 years of age? (7 yes, 0 no, 1 abstain)
In addition, the committee discussed the proposed postmarketing safety study in males and commented broadly on the appropriate approach to postmarketing safety surveillance in males.
The meeting was adjourned at 5:00 p.m.