Food and Drug Administration

Center for Drug Evaluation and Research

 

SUMMARY MINUTES

ENDOCRINOLOGIC AND METABOLIC DRUGS ADVISORY COMMITTEE #

July 27, 2001

Bethesda Holiday Inn

8120 Wisconsin Avenue, Bethesda, MD

Members Present FDA Participants

Allan Sampson, Ph.D. Gemma Kuijpers, Ph.D.

Marie Gelato, M.D., Ph.D. Bruce S. Schneider, M.D.

Deborah Grady, M.D., M.P.H. Bruce V. Stadel, M.D., M.P.H.

William Tamborlane, M.D. David G. Orloff, M.D.

Lynne Levitsky, M.D. John Jenkins, M.D.

Thomas Aoki, M.D.

Consultants Guest Experts

Robert Kreisberg, M.D. Henry Bone, M.D.

Mark Molitch, M.D.

Jody Pelosi, Ph.D.

Eric Holmboe, MD

Members Absent

Barbara Lukert, M.D.

Janet Silverstein, M.D.

Glenn Braunstein, M.D.

Executive Secretary

Kathleen R. Reedy, RDH, MS

These summary minutes for the July 27, 2001 meeting of the Endocrinologic and Metabolic Drugs Advisory Committee were approved on ____________.

I certify that I attended the July 27, 2001 meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and that these minutes accurately reflect what transpired.

 

_____________________________ _____________________________

Kathleen R. Reedy, Mark Molitch, M.D.

Executive Secretary Chairperson

 

The 76th Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee was held on July 26 and 27, 2001 at the Bethesda Holiday Inn, 8120 Wisconsin Avenue, Bethesda, Maryland, Versailles Rooms I, II and III.

On July 27, 2001, the meeting was 8:00 called to order by Mark E. Molitch, M.D., Acting Chair to consider NDA 21-318, FortéoTM (teriparatide injection, rDNA origin) Eli Lilly and Company. There were approximately 150 people in the audience. The committee had been provided with a briefing document from the sponsor and the FDA four weeks before the meeting.

Following the reading of the Meeting Statement by Kathleen Reedy, Executive Secretary, David G. Orloff, M.D., Director of the Division of Metabolic and Endocrine Drug Products extended a welcome and introduction to the topic for the day.

The Eli Lilly and Company Presentation was as follows:

Introduction:    Jennifer L. Stotka, MD, Executive Director,

US Regulatory Affairs, Eli Lilly and Company

History, Mechanism of Action and Clinical Need:  Robert Lindsay, MD, PhD
Professor of Clinical Medicine, Columbia University
                                        Chief of Internal Medicine, Helen Hayes Hospital
Nonclinical Overview:  John L. Vahle, DVM, PhD, Senior Research Pathologist,
                                        Toxicology, Eli Lilly and Company
Clinical Efficacy:  Bruce H. Mitlak, MD, Medical Director, Fortéo Product Team
                                        Eli Lilly and Company
Clinical Safety:  Gregory A. Gaich, MD , Senior Research Clinical Physician,

Fortéo Product Team, Eli Lilly and Company

Summary and Conclusions:  Bruce H. Mitlak, MD
                                       

The FDA Presentation consisted of:

Preclinical Studies: Gemma Kuijpers, Ph.D.

Efficacy: Bruce S. Schneider, M.D.

Safety: Bruce V. Stadel, M.D., M.P.H.

all of the Division of Metabolic and Endocrine Drug Products

Speakers at the Open Public Hearing were:

  1. Ronald H. White, M.S.T., Assistant Executive Director, Education, Research,
  2. and Community Affairs, National Osteoporosis Foundation

  3. Deborah Zeldow, Senior Director, Strategies and Programs,

Alliance for Aging Research

3. Peter Lurie, M.D., Assistant Director, Public Citizen Health Research Group

Following the Charge to the Committee by David G. Orloff, M.D. the participants engaged in discussion and addressed the following questions posed by the agency.

EFFICACY

  1. Based on the information presented by the sponsor in the NDA, are the data adequate to establish that teriparatide 20 ug/day is an effective dose
  1. for the treatment of postmenopausal osteoporosis to reduce fracture risk?
  2. Yes – 10 No – 0

  3. to increase BMD in men with osteoporosis?

Yes – 8 No - 2

If the answer to either of the above is no, what additional data would be required?

SAFETY

  1. Based on the information presented by the sponsor in the NDA, are the data adequate to define the safety profile of teriparatide
    1. for the treatment of postmenopausal osteoporosis?
    2. Yes – 0 No - 10

    3. for use to increase BMD in men with osteoporosis?

Yes – 0 No - 10

Consider in particular with regard to duration of use.

If the answer to either of the above is no, what additional data would be required?

APPROVABILITY

  1. Based on the data presented by the sponsor in the NDA, do you recommend approval of teriparatide
  1. for the treatment of postmenopausal osteoporosis?
  2. Yes – 10 No - 0

  3. to increase BMD in men with osteoporosis?

Yes – 5 No - 5

Consider in particular with regard to duration of use and appropriateness of teriparatide as first-line or second-line therapy for both indications.

First Line in post-menopausal osteoporosis: 4

Second Line: 5 (I abstention)

If the answer to either of the above is no, what additional data would be required?

  1. If the answer to either question in #3 is yes, given the theoretical risk for the development of osteosarcoma in humans treated with teriparatide:

a. Should duration of treatment with teriparatide be limited? If yes, please comment

on the recommended duration of use.

Two year limitation – unanimous

  1. Should use of teriparatide be recommended only for certain subgroups of patients? If yes, please comment on the recommended target population(s).
  2. Women; as second line except in cases of failure of other therapies, high fracture rates/risk; eliminate subgroups i.e. Paget’s, adolescents.

  3. Should teriparatide be limited to use as second line therapy? If yes, please comment on what criteria should be established to define second-line therapy.
  4. Yes – 5 (First line in women, second line in men – 2)

    Calcium monitoring, registry of users, monitor tumor registry, (SEER)

  5. Please comment on how the osteosarcoma findings in rodents should be addressed in labeling (e.g., Bolded Warning, Black Boxed Warning).

Bold print – 2 Black Box – 6

Patient education; nurse/educator education

POSTMARKETING/RISK MANAGEMENT

  1. If the answer to either question in #3 is yes, please provide recommendations regarding strategies for postmarketing surveillance for the possible development of osteosarcoma in teriparatide-treated patients.
  2. Case finding study to determine exposure

    Case ascertainment (to determine denominator and numerator)

    Rare occurrence, case collective

    Registry: determine patient exposure, tumor registry, national death index

    Registry: rebate card for money to increase compliance

    Get advice.

  3. If the answer to either question in #3 is yes, what, if any, postmarketing studies do you recommend?

Future studies with mature rats and increase number of exposures

Mechanistic studies in rats to understand carcinogenesis

Quality of life data with patients

Head to head with other treatments

Combination studies, and longer term studies

Diagnose and classify disease to determine therapy, i.e. anabolic or anti-resorptive.

The meeting was adjourned at 3:30 pm.

Kathleen Reedy, RDH, MS, Health Scientist Administrator

Executive Secretary, Endocrinologic and Metabolic Drugs Advisory Committee