1. PDUFA Reauthorization: Advancing Rare Disease and Orphan Drug Policies Steven Grossman, President, HPS Group, LLC To National Organization of Rare Disorders May 15, 2012 Contact: sgrossman@hpsgroup.com (301) 539-9660sgrossman@hpsgroup.com © HPS Group, LLC 2012. Permission to reprint is granted FDA Matters The Grossman FDA Report ™ www.fdamatters.com 1

2. 2012 PDUFA Amendments NORD Goals – FDA flexibility in reviewing orphan drugs – Resources for biomarkers/pharmacogenomics – Improvements in humanitarian device program Most key RD/OD provisions in both bills Strongest Set of RD/OD Improvements Since ODA

3. Rare Disease Initiative in FDA Commitment Letter  staffing of CDER/CBER Rare Disease Programs  participation with reviewers, industry & patients Broadened programming in non-traditional clinical trial design, endpoints, statistical analysis Staff training for reviewers, re approval of drugs for rare diseases Integration of RDP staff into review teams

4. Other RD/OD Priorities More rare disease expertise in AC process – Encourages FDA to use wider range of experts – Conflict of interest re-set to FACA standards Faster review/more flexibility for promising therapies for unmet (orphan) medical needs – Modernize/codify Accelerated Approval process – Speed development of drugs with strong early showing of efficacy (Break-through)

5. Other RD/OD Priorities Expansion of the Humanitarian Use Device (HUD) Program – Adults – Allow profit under certain circumstances Re-authorization and Improvements in OD grant program – More $ possible – Designation not required

6. Implementation User fee provisions become effective 10/1/12 Some parts may take years to implement (normal) Provisions a mix: some self-implementing; others will require guidance; some regulations Most RD/OD provisions will have early impact Potential barriers: – Funding – Elections

7. FDA Funding In FY 12: – BA (taxpayer) appropriations = $2.5 billion = 75% – User fees = $849M = 25% (excludes tobacco uf) – Uneven impact—drug review process 65% user fees New law increases $ and % user fees and # of fees In FY 13, FDA faces possible BA cuts & sequester Funding Cuts Will Slow All Activities Regardless of Funding Source

8. 2012 Elections and Aftermath Presidency, Senate and House at stake Regardless of who wins: deficit reduction priority If new President, then: – Possible freeze on new federal regulations – Acting commissioner for unknown period – New commissioner faces confirmation hearings No “must-pass” FDA legislative vehicles in 2013

9. Post-PDUFA Rare Disease & Orphan Drug Agenda? Multiple successes mean new dialogue later this year about priorities for rd/od community Possible FDA issues: benefit-risk standards; diagnostics; and limited population studies Possible Access issues – Reimbursement issues (e.g. off-label use) – Patient cost sharing/utilization barriers (private & state) – If ACA is overturned or repealed: status quo on uninsured, pre-existing conditions and lifetime caps