Food and Drug Administration

Center for Biologics Evaluation and Research

SUMMARY MINUTES

VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY COMMITTEE

Meeting \# 91: May 21, 2002

[Committee Members]{.underline}

Dr. Robert Daum, Chair

### +Dr. Michael Decker

Dr. Pamela Diaz

Dr. Walter Faggett

\*Ms. Barbara Loe Fisher

Dr. Judith Goldberg

Dr. Diane Griffin

Dr. Sam Katz

Dr. David Markovitz

Dr. Gary Overturf

Dr. Julie Parsonnet

Dr. David Stephens

Dr. Rich Whitley

# Temporary Voting Members

Dr. Mimi Glode

Dr. Richard Schwartz

Dr. Dixie Snider

Dr. Holli Hamiliton

# Sponsor Presenters

Dr. Steven Black

Dr. George Siber

Dr. Terhi Kilpi

# FDA Participants

### Dr. Karen Midthun 

Dr. Susan Ellenberg

Dr. Norman Baylor

Dr. Karen Goldenthal

### Dr. Douglas Pratt

Dr. Patricia Rohan

Dr. Jingyee Kou

# Committee Members Absent 

Dr. Estuardo Aguilar-Cordova

Dr. Audrey Manley

Dr. Peter Palese

[Executive Secretary]{.underline}

Dr. Jody Sachs

These summary minutes for the May 21, 2002 meeting of the Vaccines and
Related Biological Products Advisory Committee were approved on
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ .

I certify that I participated in the May 21, 2002 Meeting of the
Vaccines and Related Biological Products Advisory Committee and that
these minutes accurately reflect what transpired.

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Jody Sachs, D.P.M. Robert S. Daum, M.D.

Executive Secretary Chair

The 91^th^ meeting of the Vaccines and Related Biological Products
Advisory Committee was called to order at 8:30 a.m. EST on May 21, 2002
by the Chair, Dr. Robert Daum. The meeting addressed in **Session #1:**
Prevnar for indication in acute ottitis media, and

**Session #2:** Update on GSK Lyme Disease Vaccine (LYMErix). Both
Session 1 and 2 were open sessions.

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 world wide web at:
http://www.fda.gov/ohrms/dockets/ac/02acsdocs.htm. A copy of the agenda
is attached.

# **Session #1-Open Session**

**[Prevnar® for Acute Otitis Media (AOM) Indication]{.underline}**

The committee discussed an additional proposed indication for Prevnar
"for active immunization of infants and toddlers against otitis media
caused by *Streptococcus pneumoniae* due to capsular serotypes included
in the vaccine (4, 6B, 9V, 14, 18C, 19F and 23F)."

Data supporting this indication were provided from two controlled
clinical trials:

1)  Finnish Acute Otitis Media Trial (FinAOM)

2)  Northern California Kaiser Permanente Efficacy Trial (NCKP)

**Efficacy Against Otitis Media**

[**FinAOM (%)** **NCKP (%)**]{.underline}

Vaccine Serotype AOM 57 (44,67) 69\* (0.4,93)

Vaccine Related Serotype AOM 51 (27,67)

Non Vaccine Serotype AOM -33 (-81,1)

All Pnc AOM 34 (21,45)

Recurrent AOM 16 (-6,35) 12 (7,16)

All AOM 6 (-4,16) 7 (4,9)

Tube Placement 44[^1] (19,62) 24 (12,35)

> \* Spontaneous TM rupture

In the Finnish study, vaccine efficacy was 57% (95%CI: 44%, 67%) for AOM
episodes due to vaccine serotypes, and 34% (95%CI: 21%, 45%) for all AOM
episodes caused by pneumococci, regardless of serotype. The Finnish
study included myringotomy and cultures of the middle ear, this was not
true of the Kaiser study. Vaccine efficacy for all causes of AOM,
regardless of etiology, was 7% (95%CI: 4.1%, 9.7%), based on evidence
from the Kaiser study, and 6% based on evidence from the Finnish Study.

In summary, the Committee concluded that data derived from two efficacy
trials are adequate to demonstrate efficacy of Prevnar® against AOM
caused by vaccine serotype. However, the committee expressed concern
about the low efficacy (7%) of the vaccine against AOM regardless of
etiology and concluded that substantial clinical benefit of Prevnar in
reducing AOM regardless of etiology had not been demonstrated. The
Committee cautioned against including an indication statement as
proposed by the sponsor into the label and suggested using qualifying
language if an indication for AOM regardless of etiology were to be
added. Committee members cautioned against promoting prevention of AOM
as a benefit of Prevnar in direct-to-consumer advertising because of
concerns about unrealistic public expectations. The Committee was
concerned that promoting Prevnar as an "AOM vaccine" could potentially
compromise confidence in the existing recommendations for the vaccine
and trust in the labeling that FDA puts on a vaccine. It was noted that
an AOM indication for Prevnar® could set precedence for licensure of
additional pneumococcal conjugate vaccines for prevention of AOM.

Discussion points included:

-   The Kaiser Study demonstrated only a vaccine efficacy of 7% against
    AOM regardless of etiology. The significance of this efficacy was
    discussed.

-   The Finnish Study and the Kaiser Study used different endpoints. By
    the use of different endpoints, some felt that the supporting
    results from the Kaiser Study may/may not support the findings of
    the Finnish Study.

-   The vaccine serotype efficacy of 19F was discussed. The Finnish
    Study demonstrated that the AOM episodes due to individual vaccine
    serotypes (6B, 18C, 14, 23F, 4, 9V, 19F) ranged from 80% to 10%; 19F
    being the lowest.

-   Reduction in the use of antibiotics was discussed as a positive
    outcome with the use of the vaccine.

-   Prevnar® is currently recommended for all children under the age of
    2 years. Immunization is already advised for children and toddlers,
    and children are given the vaccine. The two trials show consistent
    efficacy.

-   Would the suggested change in the current label accurately
    communicate all the information necessary to the families of the AOM
    patients treated, as well as, the doctors treating AOM patients?
    Many members discussed their concerns with this issue. Promotional
    materials are based on the approved labeling. Inaccurate marketing
    would do more harm than good. The committee members felt that this
    was not an "AOM vaccine". Many felt that it would be a mistake by
    the company and FDA to have this marketed as an "AOM vaccine".

-   There is no minimum level of efficacy required for licensure of a
    preventive vaccine addressed by the FDA regulations or guidelines.

Recommendations were as follows:

-   Additional clinical trials for the prevention of AOM with the
    vaccine, using serology and analyzing serotypes, would be helpful to
    further evaluate the consistency of the results of the two studies.
    Continuous monitoring of serotypes is needed and more data need to
    be generated for analysis.

-   Further evaluation of the vaccine serotype 19F was suggested to find
    out why the 19F vaccine component was not effective.

-   Tympanostomy tube placement can easily be followed by ICD coding.
    Long-term tympanostomy tube follow-up on AOM vaccine patients was
    recommended.

-   Phase 4 studies might be useful. Serotype 19F efficacy, tube
    placement, antibiotic resistance, and the pursuit of non-serotype
    replacement of nasopharyngeal colonization are important issues to
    pursue.

-   Careful wording and qualifying language be used if the AOM
    indication efficacy data were to be included on the current label of
    Prevnar®. (Suggestions included using the wording that "the vaccine
    efficacy was only 7% in treating all AOM, regardless of etiology".)

-   The vote was 13 to 3 to agree that the data support the efficacy of
    Prevnar® for active immunization in infants and toddlers for the
    prevention of AOM caused by *S Pneumoniae* due to capsular serotypes
    included in the vaccine (4, 6B, 9V, 14, 18C, 19F and 23F).

## 

## Session #2 -- Open Session

**[FDA Update on the GSK-Lyme Disease Vaccine (LYMErix)]{.underline}**

The FDA informed the committee members that GSK voluntary withdrew
LYMErix from sale in February of 2002 and distribution was
discontinued. GSK cited poor sales as the reason for withdrawal. No
further vaccinations are recommended, clinical trial vaccination ended,
Dear Doctor/Investigator letters were sent, and refunds were given for
returned vaccine. Complete safety follow-up will be completed for all
clinical studies and the Phase 4 post-marketing study is to be completed
in 2006.

##### Open Public Hearings

Two Open Public Hearing sessions were announced. No one requested time
to speak in Session #1. For Session #2 there were eight requests for
speaking.

**Session #2-Open Public Hearing**

Public Speakers on Lyme Disease:

1.  Karen Vanderhoof-Forschner (Lyme Disease Foundation)

2.  Dr. Norman Latov

3.  Dr. Mark Geier

4.  David Geier

5.  Stephen Sheller, Esq.

6.  Kathy Shepanski

7.  Pat Smith (Lyme Disease Assoc.)

8.  Jenny Marra

Proceedings were adjourned at approximately 3:30 p.m. EST on May 21,
2002.

[^1]: Fin AOM follow up