# Summary Minutes of the

# Oncologic Drugs Advisory Committee

# March 12, 2008

# Location: Holiday Inn, The Ballrooms, Two Montgomery Village Avenue, Gaithersburg, MD

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# All external requests for the meeting transcripts should be submitted to the CDER, Freedom of Information office.

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# These summary minutes for March 12, 2008 Meeting of the Oncologic Drugs Advisory Committee of the Food and Drug Administration were approved on ­\_\_3/26/2008\_\_\_\_\_\_\_\_\_\_\_\_\_\_.

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# I certify that I attended the March 12, 2008 meeting of the Oncologic Drugs Advisory Committee of the Food and Drug Administration and that these minutes accurately reflect what transpired.

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# Nicole Vesely, Pharm.D. S. Gail Eckhardt, M.D.

# Designated Federal Official, ODAC Acting Committee Chair

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#  Meeting of the Oncologic Drugs Advisory Committee

# March 12, 2008

The Oncologic Drugs Advisory Committee of the Food and Drug
Administration, Center for Drug Evaluation and Research met on March 12,
2008 at the Holiday Inn, The Ballrooms, Two Montgomery Village Avenue,
Gaithersburg, MD. Prior to the meeting, members and invited consultants
were provided copies of the background material from the FDA and the
sponsor. The meeting was called to order by S. Gail Eckhardt, M.D.
(Acting Committee Chair); the conflict of interest statement was read
into the record by Nicole Vesely, Pharm.D. (Designated Federal
Official). There were approximately 250 persons in attendance. There
were 6 speakers for the Open Public Hearing session.

**Issue:** The committee discussed biologic license application (BLA)
125268, proposed trade name NPLATE (romiplostim), Amgen Inc., proposed
indication for the treatment of thrombocytopenia in adults with chronic
immune (idiopathic) thrombocytopenia purpura (ITP) who are
nonsplenectomized and have had an inadequate response or are intolerant
to corticosteroids and/or immunoglobulins; or patients who are
splenectomized and have an inadequate response to splenectomy.

**Attendance:**

**Oncologic Drug Advisory Committee Members Present (Voting):**

S. Gail Eckhardt, M.D. (Acting Committee Chair), Michael Link, M.D.,
Virginia Mason, RN (Consumer Representative), Joanne Mortimer, M.D.,
Ronald Richardson, M.D., David Harrington, Ph.D., Michael Perry, M.D.

**Special Government Employee Consultants (Voting):**

Harvey Katzen, M.D., Roshni Kulkarni, M.D., Joseph Petosa (Patient
Representative)

**Non-voting Participants:**

Gregory Curt, M.D. (Industry Representative)

Heather Mannuel, M.D., M.B.A. (Guest Speaker)

**Oncologic Drugs Advisory Committee Members Not Present:**

Maha Hussain, M.D.

Ronald Bukowski, M.D.

Gary Lyman, M.D.

**FDA Participants** (Non-Voting):

Richard Pazdur, M.D., R. Dwaine Rieves, M.D., Faranak Jamali, M.D.,
David Frucht, M.D., Steven Lemery, M.D., Suzanne Berkman, Pharm.D.

**Designated Federal Official:**

Nicole Vesely, Pharm.D.

**Open Public Hearing Speakers:**

Valentine Santos

Barbara Pruitt, Platelet Disorder Support Association

Pamela Ford

Joanne Moriarty

Joan Young, Founder and President, Platelet Disorder Support Association

James Bussel, M.D.

***The agenda was as follows:***

Call to Order and Introductions **S. Gail Eckhardt, M.D.**

Acting Committee Chair

Oncologic Drugs Advisory Committee

Conflict of Interest Statement **Nicole Vesely, Pharm.D.**

Designated Federal Official

Oncologic Drugs Advisory Committee

**=================================================================**

**[FDA Presentation]{.underline}**

Introduction to Romiplostim **David Frucht, M.D.**

> Product Quality Reviewer, Division of Monoclonal Antibodies, OBP, OPS,
> CDER, FDA

**[Guest Speaker]{.underline}** **Heather Mannuel, M.D., M.B.A**

Overview of ITP Assistant Professor of Medicine

> University of Maryland/Greenbaum Cancer Center

**[Sponsor Presentation]{.underline}** **[Amgen Inc.]{.underline}**

Background and Introduction **Joseph Miletich, M.D., Ph.D.**

Senior Vice President

> Research & Development, Amgen Inc.

Thrombopoietin (TPO) and **David Kuter, M.D., Ph.D.**

Management Professor, Dept of Medicine, Harvard Medical School

Of Immune Thrombocytopenic Director, Clinical Hematology, Massachusetts
General

Purpura (ITP) Hospital

Romiplostim in ITP: Efficacy **Dietmar Berger, M.D., Ph.D.**

And Risk Assessment Executive Director

Global Clinical Development, Amgen Inc.

Risk Management Program & **Paul Eisenberg, M.D., MPH**

Closing Remarks Senior Vice President

Global Regulatory Affairs & Safety, Amgen Inc.

**[FDA Presentation]{.underline} [BLA 125268 ]{.underline}**

Romiplostim FDA Overview **Faranak Jamali, M.D.**

> Medical Officer, Division of Medical Imaging and Hematology Products,
> OODP, OND, CDER, FDA

Romiplostim Safety Review: **Steven Lemery, M.D.**

MDS Progression Medical Officer, Division of Biologic Oncology Products,

> OODP, OND, CDER, FDA

Risk Management Considerations **Suzanne Berkman, Pharm.D.**

For Romiplostim Senior Drug Risk Management Analyst, Division of Risk
Management, OSE, CDER, FDA

Question to the Presenters

Open Public Hearing

Questions to the ODAC

and ODAC Discussion

Adjourn

Questions to the committee:

In two randomized clinical studies of adult patients with chronic immune
(idiopathic) thrombocytopenic purpura (ITP), a greater proportion of
patients who received Romiplostim experienced a \"durable platelet
response\" than patients who received a placebo (38% versus 0 in a study
of patients who had undergone splenectomy; 61% versus 5% in a study of
patients who had not undergone splenectomy). The studies were not
designed to demonstrate an effect upon bleeding rates and the observed
bleeding rates were low and generally similar between the study groups.

1.  (Discussion) Discuss the clinical importance of the durable platelet
    response rates and comment upon the extent, if any, to which the
    observed bleeding rates impact an assessment of a clinical benefit
    for Romiplostim.

    -   *The committee agreed that platelet response should be the only
        surrogate marker of efficacy.*

**Please see the transcript for detailed discussion.**

2.  (Discussion) Multiple safety risks were highlighted in the
    background documents and presentations. Discuss important
    considerations in the development of a risk management program.
    Consider the potential consequences of excessive or insufficient
    restriction of distribution, the best methods to monitor risks and
    the frequency of monitoring. For example, to what extent are the
    following aspects important components of a Romiplostim risk
    management program?

-   use limited to patients with a diagnosis of chronic ITP

-   documentation of \"qualifying\" platelet count values

-   systematic, regular assessment of all patients for significant
    clinical reactions

-   certain specific evaluations, such as bone marrow biopsy/aspirate or
    peripheral blood blast counts.

> Bullet One:

-   *The committee agreed that the use should be limited to those with
    chronic ITP.*

> Bullet Two:

-   *The panel agreed that the program should incorporate flexibility
    for physician judgment.*

-   *Overall, the panel agreed that the use of romiplostim should not be
    tied to a fixed entry criteria or platelet count.*

> Bullet Three:

-   *The panel agreed with this statement*

> Bullet Four:

-   *One panel member noted that routine bone marrow biopsy is outside
    the general scope of practice, but should be included in a study
    while another member noted that patients should be monitored closely
    since there will be a small data set.*

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-   *One panel member noted that looking at peripheral smears should be
    done prospectively*

-   *Most panel members agreed that the timing/frequency of the bone
    marrow biopsies needed to be examined*

**Please see the transcript for detailed discussion.**

3.  (Vote) Do the clinical data demonstrate a favorable risk-benefit
    profile for certain patients with chronic ITP? If \"yes,\" see
    question 4.

> ***Vote : Yes=10 No = 0 Abstain = 0***

**Please see the transcript for detailed discussion.**

> 4\. (Discussion) With respect to development of a label, discuss the
> clinical characteristics that should identify the indicated patient
> population. For example, consider whether the labeled indication
> should be limited to:

-   patients who are \"intolerant\" or who have an insufficient response
    to a [single]{.underline} course of corticosteroids and/or
    immunoglobulins,

-   patients who have failed at least two courses of ITP medications

-   patients who have undergone splenectomy.

> Bullet One

-   *Numerous panel members noted that it would be difficult to define
    intolerant or refractory, with one member noting that the product
    could be used only in 2^nd^ or 3^rd^ line therapy thereby not having
    to define failed or intolerant.*

> Bullet Two: (FDA further defined the question and asked whether
> romiplostim should be considered for those who failed
> corticosteroids/experienced side effects with corticosteroids)

-   *One panel member agreed that romiplostim should be considered based
    upon risk/benefit of prednisone and romiplostim*

-   *Panel members agreed that the physician's judgment needs to be
    considered.*

-   *FDA noted that there are several expanded access programs that
    individuals can use.*

> Bullet Three

-   *The panel agreed that romiplostim works in both splenectomized and
    non-splenectomized populations based upon the data presented*

**Please see the transcript for detailed discussion.**

The session adjourned @ approximately 2:30 p.m.