All participants will be muted as they enter the webinar.

1. All participants will be muted as they enter the webinar. Please don’t use webcams or video, audio only. This webinar is being recorded. Questions or comments can be submitted through chat option.

2. Purpose of Meeting? To educate the Food & Drug Administration (FDA) • What it is like to live with FA • Your concerns as the disease progresses • How you currently manage FA • What meaningful treatments look like • Your thoughts & experiences related to clinical trials

3. Why Should I Participate? • Opportunity to have Your Voices heard • The FDA approves all treatments for FA and needs to know what is important to you • This knowledge will impact their decision-making, and lead to better treatments and faster approvals for FA

4. Why Now? • The Patient’s Voice has historically been absent from the drug development process • until a drug was approved by the FDA (sometimes with non meaningful endpoints for patients), or • a clinical trial was failing and the drug company or FDA wanted input from actual patients to understand the problem • Want our Voices heard at the beginning of the process and throughout

5. Why Now? • FDA Safety Innovation Act became law in 2012 • Added expedited development & review of new drugs with preliminary clinical evidence of a substantial improvement over existing therapies for those with serious/life threatening diseases (FDA website) • Recognized value of Patient Input to the ENTIRE drug development process (including FDA review & decision making) (FDA website) • Stakeholder engagement = FDA Priority • Initiated a 5-year Patient Focused Drug Development Program to learn about disease impact on Patient’s lives.

6. Meeting Logistics • Who? FA patients and caregivers • When? June 2, 2017 from 8:00 am – 12:30 pm • Where? College Park Marriott Hotel & Conference Ctr. Hyattsville, Maryland • How? In-person or online via a live webcast (meeting will be video taped and recorded) * Following the FDA meeting, there will be a research update for anyone who is interested (1:30-3:00 pm)

7. Overview • Background: FDA & Drug Development • Overview: FDA Patient-Focused Drug Development • Meeting Participation • Logistics, Format and Tips • Other key information

8. Background:FDA and Drug Development

9. Drug Development and Clinical Trials Process • FDA is responsible for public health and safety. • 2 critical approval steps: • Early - reviews all drugs that go from lab to clinical trials • Investigational New Drug (IND) • Late – reviews all animal and human data to approve drug for treatment of disease • New Drug Application (NDA) Approved Therapy IND Approval NDA Approval Initial IND submission Pre-IND Meeting Safety Update Pre-BLA or NDA Meeting End of Phase 2 meeting Market Application Submission Opportunities for researchers and pharma to interact with FDA

10. Drug Discovery Researchers learn about a disease/disease process, including what organs/systems are affected and how • Identify and test thousands of molecular compounds in the lab • Which are most likely to have a positive effect on a specific target or pathway for the disease? • Once a promising compound is found: • Drug development follows a very specific path, established by the FDA, to be sure that drugs are safe and effective when approved for broad use in humans

11. Preclinical Development • Manufacturing • Laboratory studies & Animal testing (often in mice • & monkeys) • Occurs before a new drug/biologic is tested in • humans • Purpose: • Reasonably safe for initial use in humans? • Sufficiently effective against a disease target in chemical • assay tests or animal models?

12. Clinical Development – Phase 1 • If Preclinical Development is positive, Investigational New Drug Application (IND) application filed with FDA • Human clinical trials can now begin • Small trial; usually healthy human volunteers (20-80) • Purpose: • Determine drug safety & dosage • Determine most common side effects of drug • Determine how a drug is metabolized/excreted

13. Clinical Development – Phase 2 • Larger trial, with affected patient volunteers (100-300) • Note: For FA/other rare diseases, fewer patients are required • Purpose: • Evaluate safety, side effects • Evaluate pharmacokinetics and pharmacodynamics • Pharmacokinetics – how organism affects a drug • Pharmacodynamics – how drug affects an organism • Evaluate effectiveness of drug • Compare drug against placebo )

14. Clinical Development – Phase 3 • Traditionally large-scale, randomized, placebo- controlled trials with affected patient volunteers (1000-3000) • Note: For FA/other rare diseases, # of patient volunteers is < 200 • Note: For rare diseases, the FDA has several approaches for expediting the development & review of drug candidates • Purpose: • Continued assessment of effectiveness, duration of effect in • different populations etc. • Continued safety evaluation, including potential • drug-drug interactions )

15. New Drug Application (NDA) • If positive Phase 3 trial (showing safety & efficacy), a New Drug Application (NDA) is submitted to the FDA • Includes all animal & human data • Purpose: • Allows FDA to begin review process for drug approval • FDA initiates pre-NDA meeting • uncover major unresolved issues • discuss methods of statistical analysis • identify any further studies needed )

16. FDA Review • If NDA is complete: • Review Team is assigned to evaluate it • Has 6-10 months to approve drug or not • Purpose of Review: • Is drug effective for it’s proposed use? • Is the drug safe? (e.g., do benefits outweigh risks) • Are the manufacturing methods & the controls used to maintain the product quality adequate? • Review team seeks Advisory Committee input, as needed • Opportunity for patient input

17. Post-Market Safety Surveillance • Knowledge about a product will always be limited at the time of approval • Clinical studies are brief in duration and involve a limited patient population • New safety information often emerges after a product is used in a wider patient population • FDA maintains an active program in post-market safety surveillance to monitor adverse events

18. What exactly is the FDA’s role? What it does and does not do

19. Drug Development & Clinical Trials • FDA does not develop drugs • Researchers, pharmaceutical companies, and nonprofit groups conduct disease research and drug development • FDA does not test drugs in clinical trials • FDA does not run clinical trials • FDA staff are not onsite for clinical trials • Researchers conducting trials must seek FDA approval before beginning

20. Practice of Medicine & Drug Costs • FDA does not have authority to regulate the practice of medicine • FDA regulates the development & marketing of medical products • Doctors are free to prescribe FDA-approved drugs for other conditions (known as “off-label” use) • FDA does not regulate the price of medicine • Consideration of drug prices is not part of FDA’s mandate • FDA cannot base an approval decision on drug price • FDA does not even receive pricing info. during a review

21. FDA Facilitates Drug Development • FDA’s mission includes “Promoting Public Health” • Review teams have expert knowledge about drug development and clinical trials • Meets numerous times with companies throughout the drug development process • Helps companies design clinical trials & studies • Provides technical assistance • Manufacturers pay user fees under the Prescription Drug User Fee Act (PDUFA) • Supports FDA involvement in drug development & review of marketing applications

22. FDA’s Regulatory Authority • Foods, including dietary supplements • Drugs, prescription & non-prescription • Biologics, including vaccines, cellular & gene therapy products, and tissue products • Medical Devices, pacemakers, surgical implants • Electronic products that give off radiation • Cosmetics • Veterinary Products • Tobacco Products

23. For more information on FDA regulation of medical products, and other ways to get involvedhttp://www.fda.gov/ForPatients/

24. OverviewFDA Patient-Focused Drug Development(some of the following material reproduced from presentations by FDA’s Dr. Theresa Mullin and the MDF Webinar presentation)

26. Purpose of the Meetings? • FDA wanted a more systematic way to gather the patient perspective about the condition and available treatment options • Helps inform their understanding of the context for benefit/risk assessment and decision making for new drugs • Patient input helps the FDA during drug development and their review of an application for marketing a new drug

27. FA Patient Focused Meeting • Framework for panel questions came from FDA’s benefit-risk framework; represents important considerations in their decision making • We reviewed this & other disease area questions and tailored our agenda/panel questions to communicate the most important information related to FA • FDA emphasizes that: • ACTIVE PATIENT INVOLVEMENT & PARTICIPATION IS THE KEY TO THE SUCCESS OF THESE MEETINGS!

28. “Voice of the Patient” Report • FARA to prepare a written “Voice of the Patient” report after the meeting • Summary of patient & audience testimony, polling data & submitted written comments • Key communication to FDA review staff & the regulated industry about what patients most want to see in a treatment • FDA wants this information; informs them about ways to develop meaningful treatments for FA

29. Participating in the Meeting

30. Meeting Logistics • Who? FA patients & caregivers, FDA staff and pharma & biotech companies • When? June 2, 2017 from 8:00 am – 12:30 pm • Where? College Park Marriott Hotel & Conference Ctr. Hyattsville, Maryland • How? In-person or online via a live Webcast * Following the FDA meeting, there will be a research update for anyone who is interested (1:30-3:00 pm)

31. Overview of the Agenda • Welcome and introductory comments from FARA, MDA, NAF and the FDA • Two patient/caregiver panels: • How FA symptoms affect your life • How you manage symptoms and current & future approaches to treatment • Polling Questions & Moderated Discussion with audience after each panel • FDA Closing comments Moderator James Valentine

32. Discussion Questions • Panel 1: Living with FA • What 1-3 symptoms impact you the most (e.g. ataxia/walking, fatigue, speech)? • How do they affect your daily life? Examples? • How have your symptoms changed over time? • Any specific activities that are important to you that you can no longer do or do as fully? • What mostworries you about symptoms or progression? • If you could fix one symptom, what would it be?

33. Discussion Questions (cont.) • Panel 2: Current and future approaches to treating FA • How do you manage your symptoms now? (e.g. PT, surgery, cardiac medications) • How well are therapies working? • How well do they improve your ability to do specific activities important in your daily life? • What specifically would you like to see in a treatment? (short of a cure)

34. Discussion Format • For each topic, the patient/caregiver panels will speak first • Purpose: to set the foundation for the broader audience discussion • Panelists reflect a diverse range of experiences: age of onset, level of progression, key symptoms etc. • Patients and caregivers (only) in the audience and online will have a chance to answer “polling” questions • Purpose: starting point for the discussion • How? Cell phone (via text message) or through a web page • Discussion with patients & caregivers in the audience • Purpose: to build on the experiences shared by the panel • Moderator will ask questions & invite you to raise your hand to respond

35. Tips for Effective Participation • Remember FDA’s role & the purpose of the meeting • Review each question in advance • If you have something important to share, relate it to the most appropriate topic/panel question • It is OK to reiterate a feeling/experience already voiced by someone that is similar to your own, but give it a personal or unique perspective • Keep your comments concise & focused; there are many voices to be heard about this emotional topic • Comments will be collected from those online during the webcast or can be sent to FARA within 30 days

36. Participating in the Discussion • How • In person (hotel in Hyattsville, MD) •  By webcast (remotely; polling questions & written submissions) • Register  •  If attending in person (only): https://fda-patientmtg.eventbrite.com • Webinars Tuesday, April 4, 2017   12:00pm EST; 9:00am PT https://meetings.webex.com/collabs/#/meetings/detail?uuid=M1R5563TT1SC4COKP95UQQE7LK-S3WN Tuesday, April 11, 2017   8:00pm EST; 5:00pm PT https://meetings.webex.com/collabs/#/meetings/detail?uuid=M6SA9J76581QKB4RTHQ3XZWB1T-S3WN • Submit comments, with a focus on the panel questions, for up to 30 days after the meeting to: • Jane Larkindale:  jane.larkindale@curefa.org • Comments included in FA’s “Voice of the Patient” report submitted to FDA

37. Questions? Need Assistance? • The webinars will be recorded & available online if you cannot attend on 4/4 or 4/11. 4/4 link: https://www.youtube.com/watch?v=9qVEIHeJIBo • http://www.curefa.org/conference • For more information or if you have questions about participating at the FDA meeting, contact Katie Schultz, katie.schultz@curefa.org • For issue about the hotel, contact Jamie Young, jamie.young@curefa.org or by calling 484-879-6160

38. Travel Support Application • FARA has limited support funds to help cover travel & hotel expenses (only) • Applications accepted from 4/15-4/25 • Google form - https://goo.gl/forms/YAAgUqHWyPOwyLVy2 • Funding decision announced on 4/30 • Maximum of $750/family (including non family caregivers) • Room rate is capped at $139 and is included in the $750 maximum • Funds awarded on a first-come, first-serve basis

39. Summary • This is OUR OPPORTUNITY to be part of the process • We can have a meaningful impact on clinical trial design & drug development • Our (collective) voices must be heard at the beginning of the process to help: • companies design trials that meet our needs • FDA assess risks & benefits with a full understanding of the impact of FA & the patient perspective • LETS MAKE A DIFFERENCE!! • http://www.curefa.org/conference - live April 5th