1. ParentProjectMD.org Patient Engagement in Drug Development: Experiences, Good Practices, Lessons Learned

2. ParentProjectMD.org 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 About Duchenne muscular dystrophy

3. ParentProjectMD.org

4. Why are we here? A drug development ecosystem is a community of stakeholders (universities, companies, patient organizations, patients, government organizations) living in conjunction with the nonliving components of their environment (regulations, economic factors, reimbursement potential), interacting as a system. These components are linked together through clinical research cycles and funding flows. Universities Companies Patient organizations Government Patients Reimbursement Economy Regulations

5. ParentProjectMD.org Importance of the Patient Voice PATIENT VOICE IS INMPORTANT PROVIDERSGOVERNMENTINDUSTRY An organized patient voice is necessary and important for change.

6. ParentProjectMD.org Regulatory Journey Policy Partnership Include the Patient Voice BUT – Request Transparency from Regulatory Agencies Understand What was Included into the Decision Making Process – Patient Reported Outcomes (PRO) – Preference Data

7. ParentProjectMD.org 7 PPMD has been advocating for methods to assess the benefits- risks of treatments for rare disease. We have also: Validated this work Studied caregiver worries Published a white paper on benefit risk

8. ParentProjectMD.org “When it comes to terminal illnesses [the FDA’s] job should be to make sure a product is safe and that the risks and benefits presented by the producer are accurate. Our job should be to determine, given all that information, whether to give it to our children. It is an intensely personal decision that involves the parents and the child with Duchenne.”

9. ParentProjectMD.org 9 WORKING with BIO

10. ParentProjectMD.org FDA Engagement – A collaborative Community Meetings with Division of Neurology Duchenne Policy Forum (December 2013) PPMD submits Draft Guidance (June, 2014) NIH/FDA/PPMD meeting –dystrophin quantification methodologies (February, 2015) FDA releases Draft Guidance (June, 2015) Setting the stage for the draft guidance

11. ParentProjectMD.org Clinical Trial, NDA, AdComm flawed study – Outcomes, dystrophin, open label, small number – Scientific community support – 1000 people participated in the Advisory Committee – 52 speakers only 1 negative – Advisory Committee Split Vote – PDUFA Date ignored

12. ParentProjectMD.org The Decision September 19 2016 – Eteplirsen Approved (Exondys 51)

13. ParentProjectMD.org The Fallout 162 page FDA document describes agency turmoil NORD meeting Dr. Jenkins states ‘eteplirsen should not be approved’ Sarepta Therapeutics Announces Third Quarter 2016 Financial Results and … Business WireBusiness Wire15h Humana spells out its conditional Exondys 51 coverage policy — … endpts.comendpts.com1d Sarepta Therapeutics (SRPT) Stock: They Can Shake And Rattle, But Will … cnafinance.comcnafinance.com1d After 'Female Viagra,' Muscular Dystrophy Drug, Will FDA Stand … ForbesForbes1d The FDA’s Controversial Duchenne Drug Approval And The Moral … Health AffairsHealth Affairs2d FDA expert lashes out at 'worrisome' Sarepta approval in JAMA Fierce BiotechFierce Biotech2d

14. ParentProjectMD.org Learnings Rare Disease is hard Deserves the greatest degree of flexibility when making decisions Once a drug is approved, utilizing the established process – ALL STAKEHOLDERS MUST MAKE PEACE WITH THE DECISION Disruption encourages conversation. No one wants their child to receive weekly infusions, injections or for that matter oral drugs if they have no efficacy Given the trajectory of the illness, the limited life span, once safety is established and a trend toward benefit, consider adaptive licensing. Without this conversation, patients will wait and wait and wait…. Eteplirsen is approved – the Community is interested in a real-world experience to fully understand both benefit and risk.

15. ParentProjectMD.org The most important piece of the puzzle for developing therapies is the question of MEANINGFUL BENEFIT. THANK YOU!