RECOMBINANT DNA ADVISORY COMMITTEE Minutes of Meeting March 7 and 8, 2012 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health Minutes of the Recombinant DNA Advisory Committee, 3/7–8/12 Contents I. Call to Order and Opening Remarks ................................................................................................... 2 II. Review and Discussion of Human Gene Transfer Protocol #1201-1144 titled: AAV8-Mediated Low Density Lipoprotein Receptor Gene Replacement in Subjects with Homozygous Familial Hypercholesterolemia .......................................................................................................................... 2 A. Protocol Summary ........................................................................................................................ 2 B. Written Reviews by RAC Members .............................................................................................. 3 C. RAC Discussion ............................................................................................................................ 4 D. Investigator Response .................................................................................................................. 4 1. Written Responses to RAC Reviews ..................................................................................... 4 2. Responses to RAC Discussion Questions ............................................................................. 6 E. Public Comment ............................................................................................................................ 7 F. Synopsis of RAC Discussion and RAC Observations and Recommendations ............................ 7 G. Committee Motion 1 ...................................................................................................................... 7 III. Minutes of the December 13–14, 2011, RAC Meeting ........................................................................ 7 IV. Gene Transfer Safety Assessment Board Report ............................................................................... 8 A. GTSAB Report .............................................................................................................................. 8 B. RAC Discussion ............................................................................................................................ 9 C. Public Comment ............................................................................................................................ 9 V. Day 1 Adjournment .............................................................................................................................. 9 VI. Day 2 Call to Order and Opening Remarks ......................................................................................... 9 VII. Discussion of Results from Human Gene Transfer Protocol #977 titled: Direct CNS Administration of a Replication Deficient Adeno-Associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human CLN2 cDNA to Children with Late Infantile Neuronal Ceroid Lipofuscinosis .................... 9 A. Presentation .................................................................................................................................. 9 B. RAC Discussion .......................................................................................................................... 10 C. Public Comment .......................................................................................................................... 11 VIII. Review and Discussion of Human Gene Transfer Protocol #1201-1145 titled: Phase I Study of Direct Administration of AdVEGF-All6A+, a Replication Deficient Adenovirus Vector Expressing a cDNA/Genomic Hybrid of Human Vascular Endothelial Growth Factor to the Ischemic Myocardium of Individuals with Diffuse Coronary Artery Disease via Minimally Invasive Surgery ........................ 11 A. Protocol Summary ...................................................................................................................... 11 B. Written Reviews by RAC Members ............................................................................................ 12 C. RAC Discussion .......................................................................................................................... 13 D. Investigator Response ................................................................................................................ 13 1. Written Responses to RAC Reviews ...................................................................................... 13 2. Responses to RAC Discussion Questions ............................................................................. 15 E. Public Comment .......................................................................................................................... 16 F. Synopsis of RAC Discussion and RAC Observations and Recommendations .......................... 16 G. Committee Motion 2 .................................................................................................................... 17 IX. Review and Discussion of Human Gene Transfer Protocol #1201-1143 titled: A Phase II, Randomized, Active Control, Open-Label, Multi-Center Study To Evaluate the Safety and Efficacy of EPODURE for Sustained Treatment of Anemia in Hemodialysis Patients ................................... 17 A. Protocol Summary ...................................................................................................................... 18 B. Written Reviews by RAC Members ............................................................................................ 18 C. RAC Discussion .......................................................................................................................... 20 Minutes of the Recombinant DNA Advisory Committee, 3/7–8/12 D. Investigator Response ................................................................................................................ 20 1. Written Responses to RAC Reviews ...................................................................................... 20 2. Responses to RAC Discussion Questions ............................................................................. 22 E. Public Comment .......................................................................................................................... 22 F. Synopsis of RAC Discussion and RAC Observations and Recommendations .......................... 23 G. Committee Motion 3 .................................................................................................................... 24 X. Update Discussion Regarding IBC Review of Low Biosafety Risk Protocols ................................... 24 A. Presentation .................................................................................................................................. 24 B. RAC and Public Discussion .......................................................................................................... 25 C. Public Comment ............................................................................................................................ 26 1. Dr. Barney Graham .............................................................................................................. 26 2. Ms. Mary Enama .................................................................................................................. 26 3. Dr. Jan Black ........................................................................................................................ 27 XI. Discussion of Results on Human Gene Transfer Protocol #1110-1127 titled: A Phase I Study Evaluating the Use of Allodepleted T Cells Transduced with Inducible Caspase 9 Suicide Gene After Haploidentical Stem Cell Transplantation ................................................................................. 27 A. Presentation by Dr. Rooney ........................................................................................................ 27 B. Presentation by Dr. Heslop ......................................................................................................... 28 C. RAC Discussion .......................................................................................................................... 29 XII. General Public Comments ................................................................................................................. 30 A. Statement of the American Society of Gene and Cell Therapy .................................................. 30 B. Public Comment .......................................................................................................................... 31 1. Dr. Ronald Crystal ................................................................................................................ 31 2. Dr. Hildegund Ertl ................................................................................................................. 31 3. Dr. Xiang-Xiang Zhu............................................................................................................. 31 4. Dr. Stephen Dewhurst .......................................................................................................... 31 5. Dr. Barrie J. Carter ............................................................................................................... 31 6. Dr. David Schaffer ...............................................................................................................