1. Collaborative Networks as Tools for Improving Clinical Care
Pat Furlong
Keynote Speaker
November 14, 2015

2. Why are we here?
A drug development ecosystem is a community of stakeholders (universities, companies, patient organizations, patients, government organizations) in conjunction with the nonliving components of their environment (things like regulations, economic factors, reimbursement potential), interacting as a system. These components are regarded as linked together through clinical research cycles and funding flows
Universities
Companies
Patient
Organizations
Government
Patients
Reimbursement
Economy
Regulations
An ecosystem is a community of living organisms (plants, animals and microbes) in conjunction with the nonliving components of their environment (things like air, water and mineral soil), interacting as a system. These components are regarded as linked together through nutrient cycles and energy flows

3. About Duchenne muscular dystrophy
X-linked, pediatric neuromuscular disease, with onset in early childhood
Incidence rate: 1:4600 boys (30% spontaneous)
Diagnosis: 3-5 years of age
Predictable course
Progressive loss of function
100% lethal

4. CURRENT DUCHENNE
CLINICAL TRIALS

5. ADDITIONAL DUCHENNE TRIALS AND TRIALS QUEUED UP FOR 2015
DRUG
TARGET
GOAL
COMPANY/INVESTIGATOR
TIME LINE
NBD PEPTIDE
Blocks Iĸĸb in the NF-kB pathway
Reduce inflammation, boost muscle growth
Dennis Guttridge at Nationwide Childrens and TheraLogics
Need to complete IND-enabling toxicology; Seeking partner for trial
GALGT2 GENE TRANSFER
Muscle membrane-extracellular matrix interface
Decrease muscle injury
Paul Martin and Kevin Flanigan, Nationwide Children’s
Need to complete GMP manufacturing run; Phase I in 2015
MINI-DYSTROPHIN GENE TRANSFER
Muscle membrane-extracellular matrix
Jerry Mendell, Nationwide Children’s
2015
BIGLYCAN
Justin Fallon, Tivorsan
Phase I in 2015
VBP-15
NF-kB pathway
Blocks inflammation and stabilizes membrane
Reveragen
Phase I started in 2015; Phase 2 in late 2015
CAT-1004
Blocks inflammation
Catabasis
Phase I/II in 2015
(+)-EPICATECHIN
Mitochondria
Improve energettics
Cardero
Phase 1/II in 2015
TAMOXIFEN (ORAL SERM)
Estrogen Receptor
Not Known
Lee Sweeney
Phase I/II 2015; need a clinical collaborator
FOR DMD TRIAL
Ant-Inflammatory
Finding optimal steroid regimen
NIH/ R.Griggs
Phase IIII
DEFLAZACORT
Anti-Inflammatory
Extended Access Program for approval in US
Marathon
EAP in 2015
SRP-4045
Exon 45 Skip
Restores dystrophin
Sarepta
Phase I/II 2015
BMS
myostatin
Increases muscle mass
Bristol Myers Squibb
Phase I/II 2015

6. An (Evolving) Example of Stakeholder Influence
Parent Project Muscular Dystrophy
Began following the Food and Drug Administration Safety and Innovation Act (FDASIA) and Prescription Drug User Fee Act (PDUFA V)- 2012
Committed FDA to Patient-Focused Drug Development Program
Aims to inform FDA’s benefit/risk assessments and systematically obtain patient perspective on disease impact and treatment benefits
Anticipating that Duchenne/Becker would not be chosen… (
© 2015 DIA, Inc. All rights reserved.

8. PPMD Realized the Importance of Measuring Preferences
The FDA:
Wants to improve their benefit-risk framework
Is mandated to better understand the patient experience and preferences
Is interested in testimony but… deals in data

9. Beyond Testimony: PPMD Models Advocacy-Led Stated Preference Research
© 2015 DIA, Inc. All rights reserved.

10. Beyond Testimony: PPMD’s “Share Your Story”
“I understand the need for caution and care, but I also know that our children are dying. Parents should be able to decide the risk/benefit of a drug that has gone through and passed preliminary testing. I would rather my son die trying and fighting than waiting and wondering and wishing….I am one parent willing to take an educated risk!”
11/10/2018

11. PPMD Policy Forum Dec, 2013

13. FDA Draft Guidance
11/10/2018

14. Current PPMD Stated Preference Projects
Study supported by Santhera Pharmaceuticals
To what extent do parents and patients assess the pulmonary outcomes associated with the clinical trial as meaningful benefits?
What are the maximal acceptable risks, harms, and/or burden that patients and parents will be willing to accept?
Is there significant heterogeneity in the estimates of meaningful benefit or maximal acceptable risk among parents and patients?
© 2015 DIA, Inc. All rights reserved.

15. Current PPMD Stated Preference Projects
Phase II of PPMD’s benefit/risk research
Exploring meaningful benefit
Understanding risk tolerance
© 2015 DIA, Inc. All rights reserved.

16. Demands and Benefits to a Disorder Community
Highly collaborative process
Resource and time intensive
Outcomes inform advocacy
You may not get the results you “want”
A large number of people can participate, even those who cannot/do not want to testify
Requires larger sample sizes; more generalizable than testimony

17. The Vital Role of Patient/Advocacy Organizations
Collaborating with experts in stated preference research to:
Set the research agenda
Develop a meaningful study
Weigh in on interpreting the results
Disseminate to sponsors and regulators (and your community)

18. Robust Clinical Pipeline
Assessing Barriers
Robust Clinical Pipeline
Increasing numbers of trials
Increasing need for patient participants
Major sites reaching saturation/capacity
Underutilized minor sites
Site selections is important
Many sites,
More room for error

19. Clinical Trials Network
APPROVED THERAPIES
Halofuginone
NBD Peptide
CAT-1000
Clinical Trials Network
Central IRB
Certified Centers
We need to Standardize Care and improve capacity for Clinical Trials

20. Phase I: Improving and Standardizing Care Phase II
PPMD’s Approach
Phase I: Improving and Standardizing Care
Certified Duchenne Care Center Program
Phase II
Improving and Standardizing Clinical Trials

21. Improving and Standardizing Care

22. Why is Certification Important?
Certification based on same criteria
Standards for Certification
Care Considerations
Optimize and standardize care
Improve patient access to comprehensive care
Reduce variations in patient care across clinical trial sites, which will help to reduce variation in clinical trial outcomes

23. Certified Duchenne Care Center Program
Creates a network that will:
Provide standardized care in alignment with the Standards of the Certified Duchenne Care Center Program which are in agreement with the CDC Care Considerations

25. Required Clinical and Subspecialty Services
Available at each visit
Available if needed
Center director
Clinic coordination
Neuromuscular provider
Cardiology provider
Pulmonary provider
Genetic counselor
Physical therapist
Social work
Gastroenterology/urology
Orthopedics
Endocrinology
Palliative care
Surgery
Durable medical equipment
Nutrition
Orthotics
Occupational therapy
Psychology/neuropsychology/counseling/developmental peds/neurodevelopmental disabilities
Speech therapy
Wheelchair specialist

26. Comprehensive Approach to Comprehensive Care
Application, site visit,
chart reviews, decision of
CDCCP Certification Committee
Results reported
Back to the center
Certification for 5 years
Parent /patient report:
DuchenneConnect
And Clinical Experiences
Survey
Annual Center
Metrics, follow
up on committee
suggestions
Results publically available on
PPMD website

28. Improving and Standardizing Clinical Trials

30. Certified Duchenne Clinical Trials Network
Summer meeting of CDCC Directors
Assess the program at one year
Development of “Hub and Spoke” model
Assess feasibility of building a Clinical Trials Network
Common Contract
Central IRB

31. Certified Duchenne Clinical Trials Network
Criteria for certification as a Certified Duchenne Clinical Trial site
PPMD’s Drug Development Roundtable
70 global thought leaders in therapy development
Development of working group
Assess existing models of clinical trial site certification
Make recommendations of standards that can be applied across Duchenne clinical trial sites

32. Questions?

33. Thank you.