Pre-approval Communications to
Patient and Other Groups
Speakers:
Julie Tibbets, Partner, Alston & Bird LLP
Ryan Hohman, Managing Director, Policy & Public Affairs,
Friends of Cancer Research
Dara K. Levy, Director, Hyman, Phelps & McNamara, PC
Moderated by Wayne Pines, President, Regulatory Services
and Healthcare, APCO Worldwide
1
Pre-approval Communications
to Patient and Other Groups
The Importance of Patient Centered
Drug Development
Tammara M. Lewis, JD
Sr. Director, Advertising Promotion Regulatory Affairs
Endo Pharmaceuticals
The enactment of Food and Drug Safety and
Innovation Act (FDASIA) including the fifth
reauthorization of PDUFA puts patient
involvement squarely at the forefront of a
new era of drug and device innovation.
Framing the Opportunity
FDA Patient Focused Drug Development
− Patient Involvement integrated throughout FDA benefitrisk decision-making
− Provide a systematic approach and common language in
gathering patients’ input
• Adoption of common regulatory tool
• Facilitate use of PRO measures
− Commitment to implement and spur optimal drug
development and lifecycle management
• Needs based and targeted development of more effective
medicines
Framing the Opportunity
Industry Perspective
– Patients have a longstanding history of engagement
in the R&D process
• Characterization of the unmet medical need,
clinical trial participation, patient registries, PRO,
advisory boards
– Companies may advance capability to improve the
lives of patients
– Move to close the gap on drug development time and
costs
Framing the Opportunity
Patient Advocacy Groups - the bridge
between Patients, FDA regulators, Industry
and HCP’s
− Provide a myriad of services to all stakeholders
• Influence patient enrollment in clinical trials
• Development of patient registries
 Leverage information age and social media to own patient
data
• Develop and qualify PRO outcome assessment tools
Pre-Approval Communications
to Patient and Other Groups
Regulatory Considerations and
Best Practices
Julie K. Tibbets
Partner, Alston & Bird LLP
(202) 239-3444 / Julie.Tibbets@Alston.com
Overview
• Regulatory considerations
and pitfalls for pre-approval
interactions with patient
organizations
• Best practices for preapproval communications
Regulatory Considerations
Confidential
Communications
• Pre-approval promotion
• Material non-public
information
• Non-disclosure
agreements
• Consulting/scientific
advisory board
agreements*
Public
Communications
• Pre-approval promotion
• Material non-public
information
• Study recruitment
• Informed consent
• Disease awareness
• Scientific exchange
Patients &
Patient Organizations
• Can become agents of sponsors
• Agents are subject to same regulatory
standards and restrictions as sponsors
• Can create liabilities for sponsors
Pre-Approval Promotion
• Drugs: “A sponsor or investigator, or any person acting on behalf of
a sponsor or investigator, shall not represent in a promotional
context that an investigational new drug is safe or effective for the
purposes for which it is under investigation or otherwise promote the
drug.”
– 21 CFR 312.7(a)
• Devices: “A sponsor, investigator, or any person acting for or on
behalf of a sponsor or investigator shall not: (a) Promote or test
market an investigational device, until after FDA has approved the
device for commercial distribution…(d) Represent that an
investigational device is safe or effective for the purposes for which
it is being investigated.”
– 21 CFR 812.7
– But see FDA CPG 300.600 for pending 510(k)s
Pre-Approval Promotion?
• Company press releases
• Company exhibit booths
• Company presentations at medical
congresses or conferences
• Company websites
• Company responses to patient or patient
organization inquiries
Material Non-Public Information
• Public companies
• Information “reasonably certain to have a substantial
effect on the market price” or information that would be
important to a reasonable person in deciding whether to
buy or sell shares
• Immediate vs. future disclosure
Material Non-Public Information (cont’d)
• Andrew Ceresney, Director, SEC Division of Enforcement:
“Accuracy of reporting in your dealings with the FDA is
critical to getting investors the information they need. FDA
dealings and approvals are the lifeblood of your business
and are so important to investment decisions.” March 2015
• SEC and shareholder actions also possible
• SEC recommendation: share redacted FDA
correspondence publicly
• Cautionary tale
Confidential* Communications
• Non-disclosure agreements
• Consulting agreements
• Scientific advisory board meetings
*Open Payments/Sunshine Act Disclosure
– Where payment is made to a physician
Recruitment &
Informed Consent
• 21 CFR 56.109: IRB approval of “research activities” and
“information given to subjects”
– Patient organization communications as recruitment
materials/advertising?
• Patient communications  beginning of informed
consent process
• Informed consent purpose: minimize coercion and undue
influence (21 CFR 50.20)
Disease Awareness
• Non-promotional communications
• Discuss a disease or condition
• Inform consumers or health care
professionals of signs and symptoms
• Exclude reference to specific therapies
(may discuss classes of therapies)
• Examples: brochures, websites, tearsheets, exhibits at nonprofit walks, etc.
Scientific Exchange
• FDA does not restrict the scientific exchange of
information – 21 CFR 312.7(a)
• FDA has not expressly defined “scientific
exchange”
Examples
• Dissemination of medical publications
• Scientific presentations/posters
• Medical education
Scientific Personnel
•
•
•
•
•
Chief Scientific Officer
Chief Medical Officer
Clinical operations personnel
Medical affairs staff
Regulatory affairs staff
Not sales and marketing personnel
Pre-Approval Communications
BEST PRACTICES
Best Practices
• Do ensure all information and data are
truthful and accurate
• Do make clear that product is
investigational (or that new use is
unapproved)
• Do provide transparency about where
product is in development and actions
remaining for approval or clearance
Best Practices (cont’d)
• Do provide context of data – “preliminary
findings”, study design, inclusion/exclusion
criteria, endpoints, limitations, etc.
• Do provide balanced data with product
risks, adverse events
– Don’t only present efficacy data
Best Practices (cont’d)
• Don't make conclusive statements about
safety/efficacy (instead, objectively
present endpoints as “met” or “not met”)
• Don’t interpret study results (“these data
mean/indicate…”)…can be a slippery
slope
– Do be careful using investigator quotations
– Do be mindful of promotional terminology
THANK YOU
Pre-approval Communications
to Patient and Other Groups
Advocacy Organizations as a
Catalyst for Innovative
Approaches to Drug Development
Ryan M. Hohman, JD
Managing Director, Friends of Cancer Research
Accelerating the Pace
of Innovation
Washington, DC-based Think Tank & Advocacy
Organization
A unique model to create a path to better drug
development and approval through scientific, regulatory,
and legislative solutions.
Develops groundbreaking partnerships:
• Federal Agencies (FDA, NIH, NCI)
• Academic Research Centers
• Professional Societies
• Industry
• Advocacy Organizations
Policy
Science
Advocacy
Ryan Hohman, JD, Managing Director, Policy & Public Affairs
Overcoming Delays in Drug Approvals:
Breakthrough Therapy
Problem: Progress in personalized medicine is producing drugs with unprecedented impact visible early in their development, but better
regulatory tools were needed to keep pace.
Drugs showing obvious, outsized potential to help patients still were required to go through the standard review procedure.
Solution: 2011 Friends-Brookings Conference: Advocacy-initiated collaboration of experts from FDA, NIH, NCI, academia, and industry
created Breakthrough Therapy pathway to expedite the drug development process for products that show remarkable clinical activity early.
Patients get revolutionary drugs faster, industry gets their therapies to market sooner, FDA is more efficient— But didn’t happen
until advocacy got it started.
1 Year: Panel  Whitepaper  Bipartisan Legislation  New Pathway at FDA
1 Year: 100+ Applications  38 Designations (13 in cancer)  3 Full Approvals
Breakthrough in Action
As of September 24, 2015, FDA has given 28 approvals to drugs designated as Breakthrough Therapies.
• FDA lists 334* total requests for Breakthrough designation, 103 requests granted, and 180 requests denied.
www.focr.org/breakthrough-therapies
*FDA does not disclose information regarding specific drugs or sponsors.
Approved Breakthrough Drugs
Drug Name
Sponsor
Indication
PDUFA
Deadline
Approval
Date
Ofev
Esbriet
Blincyto
Boehringer Ingelheim
Idiopathic pulmonary fibrosis (IPF)
1.02.15
10.15.14
Intermune
Idiopathic pulmonary fibrosis (IPF)
11.23.14
10.15.14
Amgen
5.19.15
12.2.14
Viekira Pak
Opdivo
Kalydeco
Imbruvica
Ibrance
Lucentis
Kalydeco
Eylea
Rapamune
Orkambi
Technivie
Xuriden
Abbvie
Acute lymphoblastic leukemia
(ALL)
Hepatitis C
12.21.14
12.19.14
Bristol-Myers Squibb
Melanoma
3.30.15
12.22.14
Vertex
Cystic fibrosis
12.30.14
12.29.14
Pharmacyclics
Waldenström’s macroglobulinemia
4.17.15
1.29.15
Pfizer
Metastatic breast cancer
4.13.15
2.03.15
Genentech
Diabetic retinopathy
2.06.15
2.06.15
Vertex
Cystic fibrosis
7.5.15
3.17.15
Regeneron
Diabetic retinopathy
3.30.15
3.25.15
Wyeth/Pfizer
LAM
6.15
5.28.15
Vertex
Cystic fibrosis
7.05.15
7.02.15
Abbvie
Hepatitis C
-----
7.24.15
Wellstat Therapeutics Corp
Hereditary orotic aciduria
-----
9.04.15
Overcoming Hurdles in Clinical Trials:
Problem: Clinical trials can be inefficient, expensive, time-consuming, and infrastructure-intensive, difficult to enroll patients and often times require
expensive genetic testing.
Solution: Multi-drug, multi-arm, biomarker-driven clinical trial protocol.
A more efficient and effective model: Trial matches companies with the patients whose tumors are most genetically relevant to the therapies
they are developing.
Groundbreaking Public-Private Partnership: Five major pharmaceutical companies, Foundation Medicine, NCI, SWOG, FDA, FNIH, and
multiple advocacy organizations
Better trials for patients, more efficient for industry, increased government collaboration.
“Lung-MAP will, I think, set a standard for how we want to conduct this sort of precision medicine for cancer going forward. ” –Dr. Francis Collins, Director,
National Institutes of Health (NIH)
Nov. 2012 Leaders from industry, FDA, NCI, academic research, & advocacy developed the concept  Nov. 2013 Final trial design and first
experimental drugs announced  June 2014 Lung-MAP launched at cancer centers nationwide  October 2014: Over 350 sites across the United
States now participating
GENOMIC PROFILE SCREENING
Patients are screened using a comprehensive genomic profiling platform (FoundationOne) that looks at over 200 cancer-related genes for
genomic alterations. Instead of having to undergo multiple diagnostic tests to determine eligibility for many different studies, enrollees are
tested just once
SUB-STUDY ASSIGNMENT
Based on the results of this screening, patients are assigned to whichever one of up to five sub-studies testing different investigational
treatments best suits their genomic profile.
INNOVATIVE APPROACH
This innovative approach improves a patient’s likelihood of receiving a drug that will work for them while allowing for new therapies in
development to be added as the trial progresses.
Lung-MAP Trial Arms for Treatment
Patients with
squamous cell lung
cancer
Tumor sample analyzed
Arm C
Tumor has none of
the changes listed
here
50 %
Chemotherapy
50 % MEDI
4736
Tumor DNA has
PIK3CA gene
mutation
50%
Chemotherapy
50 %
GDC-0032
Tumor DNA has
CCND1, D2, CDK4
gene mutation
50%
Chemotherapy
50 %
Palbociclib
Tumor DNA has FGFR
gene amplification,
mutation or fusion
50 %
Chemotherapy
50 % AZD
4547
Tumors contains
high levels of cMet protein
50 %
Erlotinib
50 %
Rilotumama
b+ Erlotinib
Pre-approval Communications
to Patient and Other Groups
Patient Group/Sponsor Interactions
Dara Katcher Levy
Hyman, Phelps & McNamara, PC
DLevy@hpm.com
www.fdalawblog.net
202-737-4290
“Although it may seem odd in retrospect, the
development of new technologies intended to
improve patients’ lives has largely relied upon
expert opinions rather than asking patients and
families directly what they consider most
important. But that’s changing.”
FDA Voice – September 18, 2015 FDA Announces
First-ever Patient Engagement Advisory Committee
History of Patient Involvement in Medical Product Regulation
Late 1980’s
Early
1990’s
1990’s2000’s
• AIDS Coalition to Unleash Power (ACT UP) demonstration shut down FDA’s headquarters in Rockville
• Led to creation of FDA Office of AIDS Relations (origins of current Office of Health and Constituent Affairs)
• FDA Patient Representative Program created
• Patients are recruited to serve during FDA Advisory Committee meetings
• Started with HIV/AIDS patients, expanded to cancer patients as part of Clinton Cancer Initiative, then later to all diseases/conditions
• Office of Health and Constituent Affairs (previously Office of Special Health Issues)
• Runs FDA Patient Representative Program
• Provides direct patient assistance (e.g., expanded access, personal importation)
• Facilitates patient advocacy throughout Agency
2012
• FDASIA enacted, section 1137 “Patient Participation in Medical Product Discussions” puts focus on FDA to implement strategies to solicit
views of patients earlier in medical product during drug development (e.g., FDA-sponsors meetings)
• PDUFA V enacted, including “Patient Focused Drug Development Commitment” to host 20+ disease specific meeting with patients and
caregivers over next 5 years
2013
• OHCA launches the FDA Patient Network, an information resource for patients and patient advocates (www.patientnetwork.fda.gov)
• CDRH hosts meeting on Patient Preference Initiative, a quantitative assessment of benefit-risk preferences (building on pilot Obesity Risk
Tolerance Survey and 2012 benefit-risk guidance)
• CDER creates Professional Affairs and Stakeholder Engagement (PASE) staff as added point of contact for patient stakeholders
2014
• Parent Project Muscular Dystrophy (PPMD) submits first-ever patient-advocacy initiated guidance document to FDA
• U.S. House Energy & Commerce Committee holds hearing on “21st Century Cures: Incorporating the Patient Perspective”
• FDA opens public docket on implementation of FDASIA section 1137 “Patient Participation in Medical Product Discussions”
2015
• 21st Century Cures Act (H.R. 6) includes provision to incorporate “patient experience data” in FDA benefit-risk determinations
• CDRH establishes Patient Engagement Advisory Committee
• FDA publication of draft guidance based on PPMD submission
History of Patient Involvement in Medical Product Regulation
Late 1980’s
Early
1990’s
1990’s2000’s
• AIDS Coalition to Unleash Power (ACT UP) demonstration shut down FDA’s headquarters in Rockville
• Led to creation of FDA Office of AIDS Relations (origins of current Office of Health and Constituent Affairs)
• FDA Patient Representative Program created
• Patients are recruited to serve during FDA Advisory Committee meetings
• Started with HIV/AIDS patients, expanded to cancer patients as part of Clinton Cancer Initiative, then later to all diseases/conditions
• Office of Health and Constituent Affairs (previously Office of Special Health Issues)
• Runs FDA Patient Representative Program
• Provides direct patient assistance (e.g., expanded access, personal importation)
• Facilitates patient advocacy throughout Agency
Internet/Social Media
2012
• FDASIA enacted, section 1137 “Patient Participation in Medical Product Discussions” puts focus on FDA to implement strategies to solicit
views of patients earlier in medical product during drug development (e.g., FDA-sponsors meetings)
• PDUFA V enacted, including “Patient Focused Drug Development Commitment” to host 20+ disease specific meeting with patients and
caregivers over next 5 years
2013
• OHCA launches the FDA Patient Network, an information resource for patients and patient advocates (www.patientnetwork.fda.gov)
• CDRH hosts meeting on Patient Preference Initiative, a quantitative assessment of benefit-risk preferences (building on pilot Obesity Risk
Tolerance Survey and 2012 benefit-risk guidance)
• CDER creates Professional Affairs and Stakeholder Engagement (PASE) staff as added point of contact for patient stakeholders
2014
• Parent Project Muscular Dystrophy (PPMD) submits first-ever patient-advocacy initiated guidance document to FDA
• U.S. House Energy & Commerce Committee holds hearing on “21st Century Cures: Incorporating the Patient Perspective”
• FDA opens public docket on implementation of FDASIA section 1137 “Patient Participation in Medical Product Discussions”
2015
• 21st Century Cures Act (H.R. 6) includes provision to incorporate “patient experience data” in FDA benefit-risk determinations
• CDRH establishes Patient Engagement Advisory Committee
• FDA publication of draft guidance based on PPMD submission
Stakeholders
• FDA
• Industry
• “Umbrella” Organizations – representing patient voice in
driving policy change
– Higher level group without focus on specific disease
– Greater resources to assist smaller patient groups
• Facilitate access to Sponsors/FDA
• Report on policy initiatives
• provide a “voice” for smaller advocacy groups
• Disease-Specific Patient Advocacy Organizations –
Focus is on representing patient voice within a particular
disease state
PG Engagement Across the Research & Development Continuum
•
From Bench to Bedside and Back
• Input regarding interest of
research question to patient
community
• Providing data on unmet need &
therapeutic burden
• Fundraising and direct funding for
research to identify target
molecules
• Facilitating collaboration with NIH
• Characterizing the disease &
relevant mechanisms of action
Prediscovery
• Fundraising & direct funding for research, trial
operations support
• Assistance in selecting & recruiting optimum
clinical sites
• Clinical infrastructure support
• Helping educate/motivate patient community &
recruit for trials
• Providing patient feedback on participant
experience
• Serving on Data & Safety Monitoring Board
• Input for any trial adaptations or modifications
• Performing or participating in benefit-risk and
patient preference studies
Preclinical
FDA Review &
Approval
Phase I/II/III
• Fundraising and direct funding for research
• Providing translational tools (assays, cell & animal
models, biosamples, biomarkers, etc.)
• Helping define study’s eligibility criteria
• Natural history database & patient registry support
• Input on meaningful clinical endpoints/PROs
• Assistance on informed consent form/process
• Working with FDA on benefit-risk and draft guidance
• Accompanying sponsor to pre-IND FDA mtg to
advocate for study
• Serving on postmarket surveillance
initiatives
• Helping return study results to
participants
• Co-presenting results
• Publications/communications re:
results
• Feedback on how patient community
views results
• Natural history database & registry
support
• Working with payers on reimbursement
PAS/Outcomes
• Providing public testimony at the
FDA Advisory Committee & other
FDA hearings
• Preparing submission for newborn
screening when appropriate
* Adapted from Parkinson’s Disease Foundation materials for CTTI’s Patient Groups & Clinical Trials Project
Used with CTTI’s permission.
National Health Council and
Genetic Alliance
• White Paper published September 22,
“Advancing Meaningful Patient Engagement in
Research, Development and Review of Drugs”
cites 3 main barriers to engagement
– Regulatory and legal uncertainty
– Culture
– Communication
Sponsor/Advocacy Group
Partnerships?
• Sponsors are Engaging Patient Groups
– Clinical Trial Design
– Clinical Trial Recruitment/Patient Registry
(natural history data)
– Understanding Disease Burden and
Benefit/Risk titration
Sponsor/Advocacy Group
Partnerships?
• Patients are Engaging Sponsors
– Seeking information about clinical trials and
potential new therapies
– Partnering to provide patient-focused “voice”
in the drug development process
– Fundraising/funding research
Conflicts of Interest?
• Exclusivity of Partnership
– Funding
– Agency
Communications
• What do communications between
sponsors and patient groups look like?
– Substance of the information conveyed
– How is the information provided
– Who is the audience
• Are the communications narrowly tailored
to achieve appropriate drug development
goals?
Thank you!
Dara Katcher Levy
DLevy@hpm.com
www.hpm.com
www.fdalawblog.net
Questions?
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