Martha ArnoldPrincipal, PharmApprove

Princeton, NJ

Michael W. YoungbiomedwoRx: Life Sciences Consulting

San Diego, CA

January 21, 2010Philadelphia, PA

Preparing for Successful Interactions with ODAC

3rd Annual Forum on Oncology Commercialization Strategies

DisclaimerThe views discussed in this presentation given on January 21, 2010 at the Loews Hotel Philadelphia at the CBI 3rd Annual Forum on Oncology Commercialization Strategies are those of the presenters and do not necessarily represent the views of any associated company or client.

Objectives

To provide you with: A better understanding of the Oncology Drugs

Advisory Committee (ODAC) to increase your likelihood of a successful interaction.

A brief backgrounder on the function and make-up of ODAC

Key learnings from recent ODAC meetingsSuggested resources to use in preparing to meet

with ODACA helpful review of part of the oncology drug

approval process which will strengthen your commercialization skillset, even if you’re not going to ODAC in the near-term.

Your PresentersMartha Arnold

Principal, PharmApproveRegulatory and Commercial Strategy ConsultantProject lead on over 25 Advisory Committee

projectsLead Commercial Officer at Anesta Corp. Group Product Director, Johnson & Johnson

Michael W. YoungPrincipal, biomedwoRx: Life Sciences ConsultingSenior Dir., Alliance Marketing & Management,

Senior Director, Global Oncology Strategy ~ Eisai Oncology Franchise

Head of Marketing ~ Ligand Pharmaceuticals, Inc.Over 20 product launches in the oncology /

supportive care / specialty markets

Insurmountable Opportunities

In 1972, Congress passed the Federal Advisory Committee Act Public Law 92-963

In 2010, getting a drug or medical device to market has never been more expensive, time-consuming, or difficult.

New legislation increases the likelihood that your product will wind up in front of an FDA advisory committee.

With the road to approval becoming even tougher, just having solid data to support your product may not be enough.

Additional Hurdles

Over the past decade that the advisory panel process itself has changed.

Because of tighter conflict-of-interest rules, panelists tend to be less well-informed about your product and indication, and more concerned than ever about product safety.

The combination makes for a particularly challenging meeting.

But there are strategies and processes that can help you prepare your team, better explain the issues, and increase your chances for product approval.

About Advisory CommitteesThe Food and Drug Administration, to assist in its

mission to protect and promote the public health, uses 48 committees and panels to obtain independent expert advice on scientific, technical, and policy matters.

48 committees…Advisory committees provide FDA with independent

opinions and recommendations from outside experts on applications to market new drugs, and on FDA policies. 

The marketing applications include data to show the safety and effectiveness of human drugs. 

The outside experts receive summary information about the applications and copies of  FDA's review of the application documents.  

Advisory committees may recommend approval or disapproval of a drug's marketing application.  FDA generally follows an advisory committee's recommendation, but is not bound to do so. 

Drugs Advisory Committees

Anesthetic and Life Support Drugs Advisory Committee

Anti-Infective Drugs Advisory Committee Antiviral Drugs Advisory Committee Arthritis Advisory Committee Cardiovascular and Renal Drugs Advisory Committ

ee

Dermatologic and Ophthalmic Drugs Advisory Committee

Drug Safety and Risk Management Advisory Committee

Endocrinologic and Metabolic Drugs Advisory Committee

Gastrointestinal Drugs Advisory Committee Nonprescription Drugs Advisory Committee Oncologic Drugs Advisory Committee Peripheral and Central Nervous System Drugs Advi

sory Committee

Pharmaceutical Science and Clinical Pharmacology Advisory Committee

Psychopharmacologic Drugs Advisory Committee Pulmonary-Allergy Drugs Advisory Committee Reproductive Health Drugs Advisory Committee

ODAC According to ODACThe '''Oncology Drugs Advisory Committee'''

(ODAC) receives requests for technical and clinical evaluation of new drugs by the United States) U.S. Food and Drug Administration (FDA).

The committee, consisting of members from academic and clinical oncology biostatistics, the general public, and the pharmaceutical industry

Make non-binding recommendations to both the CDER and CBER divisions of the FDA about the advisability of approving new medications to treat cancer.

CDERThe Center for Drug Evaluation and Research

(CDER, pronounced "see'-der") is a division of the U.S. Food and Drug Administration (FDA) that monitors most drugs as defined in the FD&C Act.

The center reviews applications for new and generic pharmaceuticals, manages US cGMP regulations for pharmaceutical manufacturing, determines which medications require a medical prescription, monitors advertising of approved medications, and collects and analyzes safety data about pharmaceuticals that are already on the market.

CDER reviews New Drug Applications to ensure that the drugs are safe and effective.

Its primary objective is to ensure that all prescription and over-the-counter (OTC) medications are safe and effective when used as directed.

CBERThe Center for Biologics Evaluation and Research (CBER)

is one of six main centers for the U.S. Food and Drug Administration (FDA), which is a part of the U.S. Department of Health and Human Services. CBER is responsible for assuring the safety, purity, potency, and effectiveness of biological and related products, including:

Blood for transfusion and as a raw material for drug products Human cells, tissues, and cellular and tissue-based products Vaccines for use in humans. Allergenic extracts. Some medical devices, specifically test kits for HIV Xenotransplantation. Gene therapy and Human Cloning

ODAC Span of InfluenceAdvisory committees are the primary means

by which the FDA obtains independent scientific advice.

Four main assumptions

1) It is independent with respect to influence by either the product sponsor or by the FDA.

2) It provides ‘expert scientific advice’, because the committee members are acknowledged experts in their respective fields.

3) It advises the FDA; however, lacks the authority to make decisions to obligate the Agency.

4) It often addresses specific questions drafted by the Agency's professional staff.

Who is the ODAC Panel?Chair -- Gail Eckhardt, MD, University of Colorado (Medical

Oncology)Ralph Freedman, MD, PhD, MD Anderson (Gynecologic

Oncology)Jean Grem, MD, University of Nebraska

(Hematology/Oncology)William Kelley, DO, Yale (Medical Oncology)Michael Link, MD, Stanford (Pediatric Oncology)Patrick Loehrer, MD, Indiana University (Medical Oncology)Gary Lyman, MD, Duke (Medical Oncology/Hematology,

Biostats/Epidemiology)

13N.B. – Panel as of December 2009

ODAC Panel continued

Ronald Richardson, M.D., Mayo Clinic (Medical Oncology)Mikkael Sekeres, MD, MS; Cleveland Clinic (Medical Oncology)Margaret Tempero, M.D., UCSF (Hematology/Oncology)Wyndham Wilson, M.D., NCI (Lymphoma) Virginia Mason, R.N. (Oncology Nurse) - Consumer RepGregory Curt, M.D., AstraZeneca - non-voting Industry Rep

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Some Learnings to Share

Define Your Issues Before Messages

Start by identifying all possible FDA and committee issues.

Develop key messages strong enough to stand alone when compared to the data and issues.

This approach may seem counter-intuitive. It may appear far more logical to craft key messages first and leave the issues for later.

The opposite is true. Experience shows that ODAC Teams often expend too many hours getting the “perfectly worded message points,” only to discover they aren’t solidly supported by their data and the issues.

*With acknowledgements to the Communication Council of America

Craft Your Take Home Messages: What do the data say?

Based on the data and outside opinion, formulate key messages to emphasize in the presentation.

If the data do not support a message, don't present it. Be rigorous.

Develop a data-supported message for each section of the presentation and develop a proactive and credible title slide for each section.

“Easily Managed Safety Profile” vs. “Adverse Events”Use the team issues list to calibrate each key

message. There is little value in spending considerable time crafting an eloquently worded message if it conflicts with a previously prioritized high-risk issue.

In addition, decide which issues should be addressed pre-emptively in the presentation, and which should be saved for a question and answer period.

Selecting Presenters: Credible Is More Important Than “Good”

Assuming your pivotal clinical work has been done by good researchers, it’s often puzzling to watch how presenters are selected by companies.

ODAC teams often spend considerable time evaluating who should present. “Dr. ‘A' is a much better presenter than Dr. ‘B'” the argument goes, but Dr. ‘A' may not know the data well or treated too few patients to be credible.

With appropriate coaching, a less eloquent speaker will often be the best choice.

Knowledge is more important than smoothness, and credibility is more important than eloquence.

The Real “No Spin Zone” “Let’s 'spin' that point more,” is sometimes the

call to action in rehearsals or planning meetings. Experience shows that “spin” rarely gets drugs and biologics approved. Positive statements that exceed the strength of supporting data are “spin.”

Don’t put your approval at risk. Agency staff and advisory committee members come prepared to be skeptical.

Positive positions are critically important, however it is equally important to underpin each with supporting data, literature cites, or expert opinion.

Be Prepared to take a Direct Approach to Uncomfortable Questions

Counter-spin is answering every question directly, no matter how difficult or embarrassing.

This approach may not put a drug, biologic, or device in the best light 100% of the time, but it adds to your credibility – especially if seeking some latitude from the advisory committee because data may be less robust than planned. It is important to have “high ground” to move to following this kind of disclosure.

“We don't currently have the data you are asking for; we do have historical data based on the literature which indicate . .” vs. “I'm sorry, we don't have that data.”

Planning and Rehearsing Answers is as Important as Knowing the Answers

Some ODAC Teams have divided the team into specialty areas (regulatory, preclinical, efficacy, safety, biostatistics for example). Each specialty team takes one key issue to resolve. Teams develop a draft, bullet-form answer including a 1-2 sentence position (“high ground”) and corresponding supporting evidence (data, literature, or expert opinion). Upon completion, teams trade answers, conduct an informal peer review of another team's work, and return their comments to the original authoring team for refinement.

Once refined, to ensure other interested parties have an opportunity for input, ask a spokesperson for each specialty team to test their answer for the full team. It a quick way to get draft responses to troublesome issues within a few short hours.

Outside Experts Need to Rehearse

“They wouldn't be outside experts if they couldn't perform well,” is sometimes expressed by sponsor teams. That is not the point. It is important to know what an expert will say under pressure in the presence of his or her peers.

That pressure can be simulated by having all team members questioned by mock committees including outside experts and company representatives.

Discussions with an expert asked to sit with you at committee are valuable, but they may not reveal what that individual will actually say at the meeting.

Mock committee rehearsals, although not real life, reflect with some accuracy how team members will perform in the “real thing.”

Who Should Moderate Q & A?Logic would tell you a moderator with no

responsibilities other than getting the right question to the right person is the best approach. However, advisory committees would rather just go to the person who will answer the question.

A clinical lead who is close to the data often makes the best moderator. True, it is a heavy burden to answer questions as well as triage multi-part questions, but many former advisory committee members have expressed that since time is short, they prefer to deal with “a moderator who can address many of the issues.”

The goal: get information to the committee as directly and quickly as possible.

The Argument for Outside HelpMany journalists who cover the FDA have noted

recently that the FDA has become more cautious and sometimes “harsh” in agency reviews of drug/biologic safety and efficacy data.

Professionalism in the presentation of data and responses to division staff and advisory committee questions, therefore, has become critically important.

Get Help. You wouldn’t necessarily go to a Level 3 Trauma Center to get your appendix out. Your chance of a successful routine surgery is greater with a team that does those procedures every day.

Perspectives on ODACMartha Arnold

Your Audience: ODAC

Standing membershipOncologists across several

subspecialties, including pediatricsStatisticians, epidemiologistsConsumer/Patient representativesIndustry representatives (nonvoting)

Temporary members as chosen by FDA

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What is ODAC, not?

They are NOT your KOLs

They may NOT be expert in your therapeutic area

They are NOT FDA

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What is Your Objective?

Earn as many votes as possible

Influence the discussion

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Influence the Discussion? Isn’t it All About the Vote?

“The advisory committee is advisory. Period. It is not a judge and jury. It is not the O.J. trial. It

is not: ‘If the glove fits, you must acquit.

It is the advice we are looking at, not the vote. We are more interested in the reasons why

people are voting.”

Richard PazdurRichard PazdurBusinessWeek.com (May 2008)BusinessWeek.com (May 2008)

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8:00 am Introductory comments

8:15 Sponsor Presentation

9:00 FDA Presentation

9:45 Break

10:00 Questions from the Committee to Presenters

10:45 Public Comment Session

11:15 Questions to the ODAC and ODAC discussion

Noon Adjourn

How much time do you have?

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ProjectionScreen

FDA Team

Podium

General Audience

Videographers

Additional Sponsor Seating

Sponsor Team

Press

“Setting the Stage”

Who are Your Other Audiences?

FDAAttendees in the room

MediaAdvocacy/citizens’ groupsCompetitorsFinancial analystsGeneral public

Unseen viewers of webcastsReal time and post-meeting

Visitors to the FDA website

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As You Prepare

Messaging/Storyline is critical

Consistency

Clarity

Brevity

Three opportunities to tell your story

Briefing Package

Core Presentation

Q&A

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Making the Most of Your OpportunitiesBriefing Package

Brief, accessible, complete

Due a month prior to the meeting

2 per meeting, 4 per ODAC day

Core PresentationUp to 45 minutes

External experts and sponsor speakers

Q&AOpportunities abound, if you prepare appropriately

High expectations for data and retrieval

Making it Happen

The commitment5 to 6 months ideal timelineFor key people – 80+% time

Set a clear project planResponsibilities, deliverablesHelp to guide and manage the process

Focus on the strategy and messagingWelcome tough feedback, get it early

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Final Thoughts

One of the hardest, most stressful and exhausting experiences you’ll ever go throughAlso, one of the most rewarding and personally

satisfying

Our favorite wise words:

“Rehearse, rehearse, rehearse, and when you’re sick of it, rehearse again”

Andrew Whelton

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Recent Experience Steven M. Fruchtman, M.D., Vice President, Clinical Research, Allos Therapeutics,

Inc. on successful ODAC with Pralatrexate

Know your own data! Backwards Forwards Any which way

Practice. It gets tense in there. No matter how good a public speaker you think you are; have prepared remarks so important points are highlighted

Practice with mock committees including statisticians, clinicians, industry consultants, etc.. This should reflect the make up of the ODAC panel (i.e. if ODAC includes a peds heme/onc, practice with a peds heme/onc).

Have your company experts with you in case an unanticipated question is asked that you are not expert in answering

ODAC members are not restricted to asking any question, even if you think a SPA discussion already covered the material, or that you have an understanding with the agency

Recent Experience Elizabeth Faust, PhD, Senior Director, Medical Affairs , Gloucester

Pharmaceuticals on successful ODAC with romidepsin.

Just know that regardless of how much you’ve prepared questions and answers, something is likely to come up that wasn’t anticipated. Your answer must be based on data and responded to in an authoritative manner so knowing WHO will field certain types of questions before going into the meeting is key.

Plan backups for logistical and electronic breakdowns. If it happens (which it does), you won’t be thrown off.

You don’t know the territory well enough…get help. Talk with people who have done this many times.

Upcoming ODAC On February 10, 2010,

during the morning session, the committee will discuss new drug application (NDA) 022-481, proposed trade name PIXUVRI (pixantrone dimaleate) injection, manufactured by Cell Therapeutics, Inc.  The proposed indication (use) for this product is as a single agent treatment for patients with recurring or refractory (difficult to treat), aggressive non-Hodgkin’s lymphoma (NHL) who have received two or more prior lines of therapy.

During the afternoon session, the committee will discuss NDA 022-374, proposed trade name OMAPRO (omacetaxine mepesuccinate) for injection, manufactured by ChemGenex Pharmaceuticals.  The proposed indication (use) for this product is for the treatment of adults with chronic myeloid leukemia (CML) bearing a genetic alteration known as the Bcr-Abl T315I mutation, and who have failed prior therapy with the drug imatinib.

Oncology GroundshiftsHealthcare reform will bring a

number of seismic changes. These include: the emergence of a comparative

effectiveness modelfor cancer patients, an increased

focus on personalized medicineimproved screening and earlier

diagnosishighly motivated patient advocacy

communities committed to making sure that patients get the best treatments for their cancer

a very challenging communications environment which will include Social Media.

Thank you

Preparing for Successful Interactions with ODAC3rd Annual Forum on Oncology Commercialization Strategies

Who is ODAC? Chair

S. Gail Eckhardt, M.D.Expertise: Medical OncologyTerm: 02/16/2006 - 06/30/2010Professor and Division Head, Medical OncologyUniversity of Colorado Health Sciences Center

Designated Federal OfficialNicole Vesely, Pharm.D.Advisors and Consultants Staff (HFD-21)Center for Drug Evaluation and ResearchFood and Drug Administration5600 Fishers LaneRockville, Maryland, 20857(301) 827-7001Fax: (301) 827-6776E-mail: Nicole.Vesely@fda.hhs.gov

**Gregory Curt, M.D.Expertise: Clinical OncologyTerm: 06/10/2008 -10/31/2011U.S. Medical Science Lead, Emerging ProductsAstraZeneca Oncology

Ralph Freedman, M.D., Ph.D.Expertise: Gynecologic OncologyTerm: 05/21/2009 – 06/30/2012Clinical ProfessorDepartment of Gynecologic OncologyThe University of Texas

Who is ODAC? Jean Grem, M.D., F.A.C.P.

Expertise: Hematology/OncologyTerm: 05/05/2008 - 06/30/2011Professor of MedicineDepartment of Internal MedicineSection of Hematology/OncologyUniversity of Nebraska Medical Center

William Kelly, D.O.Expertise: Medical OncologyTerm: 05/21/2009 – 06/30/2012Associate Professor of Medicine and SurgeryYale University

Michael Link, M.D.Expertise: Pediatric OncologyTerm: 11/15/2006 - 06/30/2010Chief, Division of Hem/OncStanford University School of Medicine

*Virginia Mason, R.N.Expertise: Oncology NursingTerm: 07/01/2007 - 06/30/2011Executive DirectorInflammatory Breast Cancer Research Foundation

Ronald Richardson, M.D.Term: 02/21/2007 - 06/30/2010Expertise: Medical OncologyConsultantDepartment of Medical OncologyMayo Clinic

Mikkael Sekeres, M.D., M.S.Expertise: Medical OncologyTerm: 05/21/2009 – 06/30/2012Associate Professor of MedicineCleveland Clinic Taussig Cancer Institute

Who is ODAC? Patrick Loehrer, Sr., M.D.

Expertise: Medical OncologyTerm: 05/21/2009-06/30/2012Interim Director, Melvin and Bren Simon Cancer CenterIndiana University

Gary Lyman, M.D. M.P.H., FRCP (Edin)Expertise: Med.Onc/Hem, Biostats/Epid.Term: 02/21/2007 - 06/30/2010DirectorHealth Services and Outcomes Research Program-OncologyDuke University Medical Center

Margaret Tempero, M.D.Term: 05/05/2008 - 06/30/2011Expertise: Hematology/OncologyUniversity of California, San Francisco - UCSF Cancer Center

Wyndham Wilson, M.D.Term: 05/05/2008 - 06/30/2011Expertise: Lymphoma/NeurobiologyChief, Lymphoma Therapeutics SectionNational Cancer Institute

Additional Resources

•FDA Advisory Committee.com• www.fda.gov/AdvisoryCommittees