Gene Therapies for Rare Diseases

September 13, 2018

Rare Disease Scientific WorkshopEverylife Foundation for Rare Diseases

Washington, DC

Wilson W. BryanOffice of Tissues and Advanced Therapies (OTAT)

Center for Biologics Evaluation and Research (CBER)United States Food and Drug Administration (US FDA)

Center for Biologics Evaluation and Research(CBER)

Office of the DirectorPeter Marks, MD, PhD, Director

Celia Witten, PhD, MD, Deputy Director

Office of Vaccines Research and Review

Office of Blood Research and Review

Office of Tissues and Advanced Therapies

Office of Management

Office of Communication, Outreach, and Development

Office of Compliance and Biologics Quality

Office of Biostatistics and Epidemiology

www.fda.gov

Cell and Gene TherapyInvestigational New Drug Applications

www.fda.gov

Investigational New Drug Applications (INDs) for Gene Therapy Products, 2002-2017

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CY2013

CY2014

CY2015

CY2016

CY2017

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41

39

34

36

44

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44

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53

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72

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106

All submitted

FOLDER_IDIRA_TYPECENTER_RECEIPT_DTCURRENT_IRA_STATUSCURRENT_IRA_STATUS_DTPAST_STATUSPAST_STATUS_DTCURRENT OFFICEPARENT OFFICESPONSORIRA_TITLEPRODUCTIRA_PROPOSED_USESPONSOR_TYPEEMERGENCY_USEGENE_THERAPYCLINICAL_PHASESOM_CELL_THERAPYFAST_TRACKBREAKTHROUGHCOMBINATIONORPHAN_DESIGNATIONRARE_PEDIATRICRARE_DISEASEUSER_FEERRS

17437IND6-Apr-17ACTIVE4/6/17OTATOCTGTMemorial Sloan-Kettering Cancer CenterHuman Wilms Tumor Protein 1 Peptides (4 Synthetic Peptides, American Peptide Company) Mixed with Montanide ISA-51 VG Adjuvant (Seppic); and Administered with GM-CSF (Berlex)Multiple products listed for IND 17437Emergency - Treatment of multiple myeloma in a single patientRHEMNUFPCELL AND GENE THERAPY

17354IND9-Feb-17ACTIVE2/9/17OTATOCTGTMemorial Sloan-Kettering Cancer CenterAllogeneic Epstein-Barr Virus Cytotoxic T-LymphocytesMultiple products listed for IND 17354Emergency - treatment of EBV post-transplant lymphoproliferative diseaseRHEMS3NUFPCELL AND GENE THERAPY

17544IDE9-Jun-17APPROVED7/3/17OTATOCTGTMemorial Sloan-Kettering Cancer CenterMagnetic-Activated Cell Sorter (CliniMACS, Miltenyi) TCR alpha/beta and CD19 T-cell depletion PBSC; conditioningMultiple products listed for IND 17544Leukocyte Adhesion Deficiency Type 1RH2NUFMDEVICES

17756IND4-Oct-17ACTIVE10/10/17OTATOCTGTMemorial Sloan-Kettering Cancer CenterEmergency Single Patient Use of Vigil Vaccine: Autologous Tumor Cells Transfected with bifunctional short hairpin ribonucleic acid furin and granulocyte macrophage-colony stimulating factor, radiated administered by injection.Tumor Cells (Autologous) Transfected with Recombinant Human Granulocyte Macrophage Colony Stimulating Factor Gene (DNA Plasmid, FANG)Treatment of Ewing sarcomaRHSPG6NUFPCELL AND GENE THERAPY

17770IDE13-Oct-17DISAPPROVED11/9/17OTATOCTGTMemorial Sloan-Kettering Cancer CenterAllogeneic, HLA-Compatible Unrelated and HLA Mismatched Related, G-CSF Mobilized, T-cell depleted Peripheral Blood Stem Cells, CD34+ Selected with the Magnetic-Activated Cell Sorter (CliniMACS, Miltenyi), ChemotherapyMultiple products listed for IND 17770Treatment of patients with Fanconi AnemiaLacking a Genotypically Identical Donor and severe hematologic disease.RH2S1NUFMDEVICES

17420IND29-Mar-17ACTIVE3/29/17OTATOCTGTMemorial Sloan-Kettering Cancer CenterRapidly Generated Peptide Stimulated Multivirus-directed Specific Cytotoxic T-Lymphocytes derived from Allogeneic PBMCs and Pulsed with CytokinesNo product listed for IND 17420Emergency - Treatment of BK viremia and adenoviremia in a single patient.RHEMS3NUFPCELL AND GENE THERAPY

17355IND10-Feb-17ACTIVE2/10/17OTATOBRRMemorial Sloan-Kettering Cancer CenterCytomegalovirsu Cytotoxic T-Lymphocytes (CMV-CTLs)allogeneic CMV Specific Cytotoxic T lymphocytesEmergency - treatment of CMV resistant reactivation in drug resistent patient (donor derived) post-stem cell transplantRHEMS5NUFPCELL AND GENE THERAPY

17651IND8-Aug-17ACTIVE9/7/17OTATOCTGTMemorial Sloan-Kettering Cancer CenterAllogeneic Matched Related TCR alpha beta and CD19 B-Cell depleteion of PBSC using the Magnetic-Acrtivated Cell Sorter (CliniMACS)Multiple products listed for IND 17651Treatment of Wiskott-Aldrich SyndromeRHEMS1NUFPCELL AND GENE THERAPY

17334IND27-Jan-17ACTIVE2/24/17OTATOCTGTMemorial Sloan-Kettering Cancer CenterEGFRr/BCMA-41BBz CAR T Cells;Dynabeads CD3/CD28 CTS; Defined Composition CD4 and CD8 T CellsNo product listed for IND 17334Treatment of multiple myelomaRHG42NUFPCELL AND GENE THERAPY

17346IND22-Feb-17ACTIVE5/16/17HOLD3/24/17OTATOCTGTNational Cancer InstituteCDX-1401 (Celldex); Poly-ICLC ; SGI-110 (Decitabine), and Atezolizumab (MPDL3280A)No product listed for IND 17346metastatic or unresectable malignancy for which standard curative or palliative measures do not exist or are no longer effectiveCM2NUFPCELL AND GENE THERAPY

17311IND19-Jan-17ACTIVE2/18/17OTATOCTGTNational Cancer InstituteHerpes Simplex Type-1 Virus Encoded with Human Granulocyte-Macrophage Colony-Stimulating Factor (rHSV-1hGM-CSF); Oncolytic Vaccine (Imlygic) [Talimogene laherparepvec] in combination with RadiationHerpes Simplex Viruse Type-1 Virus Encoded with Human GM-CSF(rHSV-1hGM-CSF)Treatment for localized soft tissue sarcomaRHG52NUFPCELL AND GENE THERAPY

17889IND19-Dec-17ACTIVE12/19/17OTATOCTGTBaylor College of MedicinePartially HLA-Matched AdV-Directed VSTs (Viralym-A)No product listed for IND 17889Emergency - treatment of adenovirus infectionRHEMS3NUFPCELL AND GENE THERAPY

17774IND18-Oct-17WITHDRAWN11/22/17OTATOCTGTNational Institute of Allergy and Infectious DiseasesHaploidentical Transplant Selected with CLiniMACS CD34 Reagent System with Alemtuzumab, Busulfan and Total Body Irradiation (TBI) with Post-Transplant Cyclophosphamide (HaploTransplant CGD with post CTX)No product listed for IND 17774Treatment of Chronic Granulomatous DiseaseCM1S1NUFPCELL AND GENE THERAPY

17374IDE22-Feb-17APPROVED5/16/17OTATOCTGTGrupp MD PhD, Stephan AMagnetic- Activated Cell Sorter (CliniMACS, Miltenyi) for TCR??+/CD19+ Depeletion of G-CSF or GM-CSF Mobilized Allogeneic Unrelated or Partially Matched Related Peripheral Stem Cells; ChemotherapyMultiple products listed for IND 17374Expanded access for patients who lack a fully HLA matched sibling donor, and who are candiates for allogeneic hematopoietic stem cell transplant. (malignant and non-malignant diseases)RH1S1NUFMDEVICES

17351IND8-Feb-17ACTIVE3/10/17OTATOCTGTNational Institute of Allergy and Infectious DiseasesAutologous Ex-Vivo Expanded CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells (Poly Tregs)T regulatory cellsTreatment of Adults with Active PemphigusRH1S3NRARE DISEASEUFPCELL AND GENE THERAPY

17846IND20-Nov-17ACTIVE12/20/17OTATOCTGTNational Institute of Allergy and Infectious DiseasesAllogeneic Bone Marrow-Derived Mesenchymal Stem Cells (hBM-MSC)Allogeneic Bone Marrow Derived Mesenchymal Stem CellsTreatment of adult recipients of living donor kidney transplant with co-stimulatory blockadeRH1S3NUFPCELL AND GENE THERAPY

17497IND16-May-17ACTIVE6/14/17OTATOCTGTNational Institute of Allergy and Infectious DiseasesAllogeneic Bilateral Orthotopic Lung Transplant (BOLT) in tandem with Partially HLA Matched, CD3+/CD19+ Depleted Cadaveric Bone Marrow Transplant using the Magnetic-Activated Cell Sorter (CliniMACS, Miltenyi), Hydroxyurea, Rituximab, Alemtuzumab, ATG, and ThiotepaMultiple products listed for IND 17497Treatment of patients with lung or intestinal end organ failure in concert with severe immune deficiencyRH2S1NRARE DISEASEUFPCELL AND GENE THERAPY

17803IND31-Oct-17ACTIVE11/30/17OTATOCTGTRoswell Park Cancer InstituteCDX-1401/Poly-ICLC in combination with Decitabine and NivolumabMultiple products listed for IND 17803Myelodysplastic Syndromes (MDS) or Low Blast Count AMLRH16UFPCELL AND GENE THERAPY

17590IND6-Jul-17ACTIVE8/4/17OTATOCTGTRoswell Park Cancer InstituteNY-ESO-1 Protein with MIS416 Vaccine in Combination with SirolimusNY-ESO-1 Cancer VaccineInducing Anti-Tumor Immunity in Ovarian, Fallopian Tube and Primary Peritoneal CancerRH1NUFPCELL AND GENE THERAPY

17410IND20-Mar-17ACTIVE4/19/17OTATOCTGTRoswell Park Cancer InstituteNY-ESO-1 TCR/ dn TGF(beta)RII transgenic T cellsMultiple products listed for IND 17410Advanced malignanciesRHG41NUFPCELL AND GENE THERAPY

17527IND5-Jun-17ACTIVE7/5/17OTATOCTGTRoswell Park Cancer InstituteAutologous PBMNC Transduced with Retroviral Vector NY-ESO-1 TCR in Combination with DecitabineMultiple products listed for IND 17527Treatment of recurrent or refractory ovarian cancerRHG41NUFPCELL AND GENE THERAPY

17521IND17-Nov-17HOLD12/13/17HOLD12/13/17OTATOCTGTMaxcyte IncAutologous Peripheral Blood Leukocytes, Transfected via Electroporation to Express Human Mesothelin Chimeric Antigen Receptor mRNAMCY-M11Platinum Resistant High Grade Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube or Peritoneal MesotheliomaCMG11NUFPCELL AND GENE THERAPY

17891IND21-Dec-17PENDING12/21/17OTATOCTGTRibas MD PhD, AntoniRV-NYESO TCR PBMC, LV-NYESO TCR/sr39TK PBSCNo product listed for IND 17891NY-ESO-1-positive relapsed or relapsed and refractory multiple myelomaRHG41NUFPCELL AND GENE THERAPY

17471IND1-May-17ACTIVE5/26/17OTATOCTGTRibas MD PhD, AntoniRV-NYESO TCR PBMC; LV-NYESO TCR/sr39TK PBSCNo product listed for IND 17471Locally advanced or metastatic NY-ES0 -1 positive cancerRHG41NUFPCELL AND GENE THERAPY

17743IND27-Sep-17HOLD10/27/17HOLD10/27/17OTATOCTGTTissueTech IncAllogeneic Human Umbilical Cord Placental Tissue, Cryopreserved; Generic: Cryopreserved Human Umbilical Cord; Code: TTAX02Umbilical Cord Tissue, Allogeneic, HumanTo promote wound healing and closure of developmental defects during in-utero repair of severe spina bifidaCM3S1NRARE DISEASEUFPCELL AND GENE THERAPY

17890IND19-Dec-17PENDING12/19/17OTATOCTGTCity of Hope National Medical CenterHER2(EQ)BB /CD19t+ T cellsNo product listed for IND 17890Recurrent or refractory malignat gliomaRHG41NUFPCELL AND GENE THERAPY

17432IND5-Apr-17ACTIVE4/7/17OTATOCTGTCity of Hope National Medical CenterHLA-matched BK specific Cytotoxic T lymphocytes (BK CTLs)No product listed for IND 17432Individual patient IND under expanded access for non-emergency use using BK specific CL lines generated by ex-vivo expansion in a post-transplant patient (DF) with BK virus infection.RHEMS3NUFPCELL AND GENE THERAPY

17638IND1-Aug-17ACTIVE8/31/17OTATOCTGTCity of Hope National Medical CenterAllogeneic CD4+ T-cell-depleted HPC with Cyclophosphamide, Pentostatin, Anti-thymocyte globulinAllogeneic Hemopoietic Stem CellsSickle Cell DiseaseRH1S3NUFPCELL AND GENE THERAPY

17501IND9-Jun-17ACTIVE7/7/17OTATOCTGTCelgeneAutologous CD4+/CD8+ T Cells Expressing CD19 Chimeric Antigen Receptor(JCAR017)No product listed for IND 17501Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL)CMG41NORPHAN DESIGNATIONUFPCELL AND GENE THERAPY

17761IND5-Oct-17ACTIVE11/3/17OTATOCTGTUniv of TexasOff-the-shelf, Expanded, Most Closely HLA Matched, Allogenic Adenovirus-Specific T cellsNo product listed for IND 17761Adenovirus related disease in immunocompromised patientsRH1S3NUFPCELL AND GENE THERAPY

17876IND12-Dec-17PENDING12/12/17OTATOCTGTUniv of TexasPembrolizumab, Clostridium novyi-NTNo product listed for IND 17876Refractory Solid TumorsRHG818UFPCELL AND GENE THERAPY

17742IND10-Oct-17ACTIVE11/9/17OTATOCTGTUniv of TexasHPV-DP-5P and HPV-DP-7P peptide vaccine and Utomilumab VaccineMultiple products listed for IND 17742Immunotherapy for HPV-16-positive incurable oropharyngeal cancerRH2NUFPCELL AND GENE THERAPY

17344IND6-Feb-17ACTIVE8/16/17HOLD3/8/17OTATOCTGTUniv of TexasAutologous IL-21-Primed CD8+ Tumor Antigen-Specific T CellsMultiple products listed for IND 17344Treatment of Platinum Resistant Ovarian CancerRH1S1NUFPCELL AND GENE THERAPY

17757IND4-Oct-17ACTIVE11/3/17OTATOCTGTUniv of TexasAllogeneic Umbilical Cord Blood (UCB) Derived NK Cells Expanded Ex VivoUmbilical Cord Blood (UCB) Derived NK CellsTreatment of Solid TumorsRH1S3NUFPCELL AND GENE THERAPY

17656IND11-Aug-17ACTIVE9/10/17OTATOCTGTUniv of TexasAllogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells administered by Intravenous Infusion or Transendocardial InjectionMultiple products listed for IND 17656Patients with Recent Onset of Anthracycline-Associated CardiomyopathyRH1S3NUFPCELL AND GENE THERAPY

17621IND21-Jul-17WITHDRAWN8/9/17OTATOCTGTUniv of TexasUtomilumab and ISA101b Peptide VaccinationMultiple products listed for IND 17621Treatment for HPV-16-Positive Incurable Solid TumorsRH2NUFPCELL AND GENE THERAPY

17428IND31-Mar-17ACTIVE4/28/17OTATOCTGTUniv of TexasAutologous T-cells Transduced with Lentiviral Vector Expressing CD33-Specific Chimeric Antigen Receptor Gene (CD33-CAR-T cells)CD3+ T cells genetically modified using a lentiviral vector (INXN-2006) to co-express a CD33-specific CAR and the HER1t depletion markerPatients with Relapsed or Refractory CD33-Positive Acute Myeloid LeukemiaRHG41NUFPCELL AND GENE THERAPY

17356IND13-Feb-17ACTIVE3/15/17OTATOCTGTUniv of TexasAutologous CD8+ Antigen-Specific T Cells and Anti-CTLA4Multiple products listed for IND 17356For patients with metastatic uveal melanomaRH1S1NUFPCELL AND GENE THERAPY

17321IND13-Jan-17ACTIVE4/11/17HOLD2/10/17OTATOCTGTUniv of TexasAllogeneic Donor Umbilical and Cord Blood derived CAR-CD19-CD28-Zeta-2a-iCasp9-IL15 Transduced NK CellsAllogeneic Donor Umbilical and Cord Blood derived CAR-CD19-CD28-Zeta-2a-iCasp9-IL15 Transduced NK CellsTreatment for relapsed/refractory B-lymphoid malignanciesRHG42NUFPCELL AND GENE THERAPY

17378IND23-Feb-17ACTIVE3/25/17OTATOCTGTUniv of TexasEx-Vivo Expanded using MSC Derived from Bone Marrow, Fucosylated and Unmanipulated Alllogeneic unrelated Cord Blood, chemotherapyMultiple products listed for IND 17378Enhance homing and engraftmentRH2S39UFPCELL AND GENE THERAPY

17314IND6-Jan-17ACTIVE5/5/17HOLD2/3/17OTATOCTGTUniv of TexasNatural Killer (NK) Cells derived from ex vivo-expanded Cord Blood, Combined with Rituximab-High Dose Chemotherapy and Autologous Stem Cell TransplantMultiple products listed for IND 17314Immunotherapy for B-cell non-Hodgkin's lymphomaRH2S3NUFPCELL AND GENE THERAPY

17731IND19-Dec-17PENDING12/19/17OTATOCTGTAmgen IncAutologous, CAR-T cells targeting delta-like ligand 3 (DLL3), transduced with third-generation SIN HIV-1 lentiviral vector, AMG 119Multiple products listed for IND 17731Relapsed/Refractory Small Cell Lung CancerCMG41NUFPCELL AND GENE THERAPY

17383IND27-Feb-17ACTIVE3/29/17OTATOCTGTFred Hutchinson Cancer Research CenterAutologous T-cells Transduced with Lentiviral Vector Expressing CD20-specific Chimeric Antigen Receptor GeneNo product listed for IND 17383Treatment of Relapsed or Refractory B Cell Non-Hodgkin LymphomasRHG12NUFPCELL AND GENE THERAPY

17663IND14-Aug-17ACTIVE8/16/17OTATOCTGTFred Hutchinson Cancer Research CenterAutologous Peripheral Blood T cells Transduced with Retroviral Vector (BPZ-1002; SFG.iCasp9.2A.SLL-TCR) Expressing human T Cell Receptor (TCR) alpha and beta chains for the Preferentially Expressed Antigen in Melanoma (PRAME)-derived peptide SLLQLIGL (BPX-701 T cells); Following Chemotherapy; AP1903 Administered Only for Uncontrolled BPX-701 ToxicityMultiple products listed for IND 17663Single patient treatment of relapsed or refractory acute myeloid leukemiaRHSPG46UFPCELL AND GENE THERAPY

17855IND22-Nov-17ACTIVE12/21/17OTATOBRRNational Institute of Diabetes, Digestive, & Kidney DiseasesHepatitis B Immunoglobulin (human) and Peginterferon alfa-2aMultiple products listed for IND 17855Treatment of Chronic Hepatitis B VirusRH2NUFPHEMATOLOGICS

17455IDE20-Apr-17APPROVED5/17/17OTATOCTGTMayo ClinicCytori Celution SystemNo product listed for IND 17455Bilateral Pre-collapse Femoral Head OsteonecrosisCM1S1NUFMDEVICES

17473IND23-Jun-17HOLD7/20/17HOLD7/20/17OTATOCTGTPfizer IncPF-06755347 (Recombinant Multimerized Human IgG1 Fc)recombinant human Fc fragment containing human (h) Fc1 (hinge, CH2 and CH3 regions)Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP)CM1NORPHAN DESIGNATIONUFPCELL AND GENE THERAPY

17659IND1-Sep-17ACTIVE9/29/17OTATOCTGTBioMarin Pharmaceutical IncAdeno-Associated Virus Serotype 5 (AAV5) Expressing SQ form of Human Factor VIII (hFVIII-SQ) (BMN 270)Adeno-Associated Virus Serotype 5 (AAV5) Vector Expressing hFVIII-SQ.treatment of Hemophilia ACMG53Breakthrough Therapy DesignationNORPHAN DESIGNATIONUFPCELL AND GENE THERAPY

17217IND9-Jan-17ACTIVE2/8/17OTATOCTGTLudwig Institute for Cancer Researchdurvalumab (MEDI4736), Adenovirus Vector (Ad5/3-D24-GMCSF), Expressing GM-CSF (ONCOS-102)Adenovirus Vector Type 3 (Ad5/3-D24-GMCSF)Treatment of peritoneal cancerRHG51NUFPCELL AND GENE THERAPY

17480IND25-May-17ACTIVE6/23/17OTATOCTGTLudwig Institute for Cancer ResearchmRNAs Encoding Tumor Specific Antigens (MUC-1, Survivin, NY-ESO-1, 5T4, MAGE-C2 and MAGE-C1) with Durvalumab and Tremelimumab Administrated IntradermallyMultiple products listed for IND 17480Non-small cell lung cancerRHG615UFPCELL AND GENE THERAPY

17557IND19-Jun-17ACTIVE7/19/17OTATOCTGTGenentech IncRO7198457, Personalized Cancer Vaccine (PCV)ROT 198457 RNASolid TumorsCM18UFPCELL AND GENE THERAPY

17624IND24-Jul-17ACTIVE8/23/17OTATOCTGTUniv of Pennsylvania Medical CenterAutologous Dendritic Cells Derived from Peripheral Blood Mononuclear Cells, Expanded with Interleukin-4, Granulocyte-Macrophage Colony-Stimulating Factor; Pulsed with Synthetic Tumor-Stem Cell Associated Antigens [AIM-2, MAGE-1, gp100, HER-2, IL-13Ra2] ICT 107-301Dendritic Cells Derived from Peripheral Blood Mononuclear CellsSingle Patient Use for Newly Diagnosed Glioblastoma MultiformeRHSPS4NUFPCELL AND GENE THERAPY

17849IND21-Nov-17ACTIVE12/21/17OTATOCTGTUniv of Pennsylvania Medical CenterAutologous T cells Transduced with Lentiviral Vector (AntiBCMAbbz human) Expressing B-cell Maturation Antigen (BCMA)-specific Chimeric Antigen Receptor (CART-BCMA) with or without Autologous CD3+ T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with self-inactivating (SIN) Lentiviral Vector (CD19bbz-human Lot# 060713S12) Expressing Humanized CD19 Chimeric Antigen Receptor (huCART19); and chemotherapyMultiple products listed for IND 17849Treatment of multiple myelomaRHG41NUFPCELL AND GENE THERAPY

17871IND6-Dec-17PENDING12/6/17OTATOCTGTFuchs MD, Ephraim JAllogeneic HLA-matched or HLA-haploidentlcal Bone Marrow Transplant and Unstimulated Lukapheresed Peripheral Blood (DLI; T Cells) Donors that have been vaccinated with VGX-3100 (IND 13683; Inovio vaccine) via electroporatlon by the Cellectra 2000; ChemotherapyNo product listed for IND 17871Treatment of recurrent, human papillomavlrus associated (HPV*) oropharyngeal squamous cell carcinoma (OPSCC).RHG61S1NUFPCELL AND GENE THERAPY

17906IND28-Dec-17ACTIVE12/28/17OTATOBRRNot EnteredBPX501 (Bellicum)No product listed for IND 17906Emergency - Second dose to boost antileukemia effect, has residual diseaseEM

17893IND23-Dec-17ACTIVE12/23/17OTATOCTGTNot EnteredtisagenlecleucelMultiple products listed for IND 17893Emergency - Yes, for the treatment of relapsed refractory ALLEM

17901IND26-Dec-17ACTIVE12/26/17OTATOCTGTNot Enteredtisagenlecleucel (antiCD19 CAAR T cell)Multiple products listed for IND 17901Emergency - need approval to porceed with manufacturingEM

17867IND1-Dec-17ACTIVE12/1/17OTATOCTGTNot EnteredCV-MG01No product listed for IND 17867Emergency - Treatment of myasthemia gravisEM

17865IND29-Nov-17ACTIVE11/29/17OTATOCTGTNot EnteredAutologous Tumor Infiltrating Lymphocytes Cultured with OKT3, Interleukin-2, and Allogeneic Mononuclear Feeder CellsNo product listed for IND 17865Emergency - Treatment of melanoma in a single patientEMS3UFPCELL AND GENE THERAPY

17492IND12-May-17ACTIVE5/12/17OTATOCTGTNot EnteredSL-701, Multivalent Glioma-Associated Antigen Vaccine, Via Subcutaneous InjectionNo product listed for IND 17492Emergency - Treatment of glioblastoma in 4 patientsEMUFPCELL AND GENE THERAPY

17577IND28-Jun-17ACTIVE6/28/17OTATOCTGTNot EnteredAllogeneic bone marrow-derived mesenchymal stem cellsNo product listed for IND 17577Emergency - primary progressive multiple sclerosisEM

17641IND1-Aug-17EM DENIED8/1/17OTATOCTGTNot EnteredAutologous Adipose Derived Stromal Vascular Fraction and ACAM200 Vaccinia VirusNo product listed for IND 17641Emergency - Treatment of papillary thyroid carcinomaEMG1

17711IND7-Sep-17ACTIVE10/6/17OTATOCTGTCowan MD, Morton JAutologous, bone marrow derived CD34+ cells transduced with lentiviral vector, expressing the human cDNA for DCLRE1C (Artemis) with the human Artemis promoterMultiple products listed for IND 17711Artemis-deficient severe combined immunodeficiency disease (ARTSCID)RHG11NUFPCELL AND GENE THERAPY

17313IND6-Jan-17ACTIVE2/3/17OTATOCTGTKurtzberg MD, JoanneAllogeneic human cord tissue-derived mesenchymal stromal cells (hCT-MSC)Allogeneic human cord-tissue mesenchymal stromal cells (hCT-MSC)Treatment of children with autism spectrum disorder (ASD)RH1S3NUFPCELL AND GENE THERAPY

17512IND23-May-17EXEMPT6/22/17OTATOCTGTRizzieri MD, David AG-CSF-mobilized peripheral blood stem cells (G-PBSCs)No product listed for IND 17512Acute Myeloid LeukemiaRH3S5NUFPCELL AND GENE THERAPY

17763IND5-Oct-17ACTIVE11/3/17OTATOCTGTMendell MD, Jerry RrAAVrh74.MHCK7.Micro-Dystrophin, Non-Replicating, Recombinant Adeno-Associated Virus, Seroype rh74 Containing a Human Micro-Dystrophin Gene Controled by the Muscle-Specific MHCK7 PromoterrAAVs, seroype rh74 expressing human micro-dystrophin with a muscle-specific [MHCK7] promoter (rAAVrh74.MHCK7.Micro-dystrophin)Duchenne muscular dystrophyRHG51NUFPCELL AND GENE THERAPY

17650IND1-Sep-17ACTIVE9/29/17OTATOCTGTBavarian Nordic A/SVaccinia Virus Vector (BN-Brachyury) and Fowlpox Virus Vector (FPV-Brachyury), Both Expressing Human Brachyury TAA, LFA-3, B7.1, and ICAM-1 GenesMultiple products listed for IND 17650Treatment of cancers that highly express Brachyury Tumor Associated Antigen (lung, ovarian, breast, prostate, colorectal, pancreatic or chordoma)CMG52NUFPCELL AND GENE THERAPY

17487IND10-May-17ACTIVE6/9/17OTATOCTGTCox Jr MD, Charles SAutologous Umbilical Cord Blood Stem Cells for Individual Patient Expanded AccessAutologous Cord Blood Stem CellsCerebral palsyRHSPS3NUFPCELL AND GENE THERAPY

17396IND8-Mar-17ACTIVE4/6/17OTATOCTGTKrance MD, Robert AAllogeneic Mesenchymal Stem CellsAllogeneic Bone Marrow Derived Mesenchymal Stem CellsAplastic anemiaRHEMS2NUFPCELL AND GENE THERAPY

17726IND4-Oct-17WITHDRAWN11/1/17OTATOBRRCSL BehringImmune Globulin Intravenous (Human), Privigen (IgPro10)Immune Globulin (Human)Chronic Immune Thrombocytopenic Purpura (ITP)CM4NUFPHEMATOLOGICS

17350IND7-Feb-17ACTIVE2/28/17OTATOCTGTParney MD PhD, Ian FAutologous Dendritic Cells Derived from (PBMC) CD14 Selection and Pulsed with Allogeneic Tumor Lysate (ALTL-DCV)Multiple products listed for IND 17350Single patient use for recurrent glioblastomaRHSPS4NUFPCELL AND GENE THERAPY

17833IND15-Nov-17ACTIVE11/15/17OTATOCTGTTalano MD, Julie-AnBPX-701No product listed for IND 17833Emergency - Treatment of refractory AMLRHEMG4NUFPCELL AND GENE THERAPY

17625IND24-Jul-17ACTIVE8/23/17OTATOCTGTGillanders MD, William ENeoantigen DNA Vaccine +/- DurvalumabMultiple products listed for IND 17625Triple-Nagative Breast Cancer Disease following Standard ChemotherapyRHG515UFPCELL AND GENE THERAPY

17596IND13-Jul-17ACTIVE8/10/17OTATOCTGTGillanders MD, William ENeoantigen DNA VaccineMultiple products listed for IND 17596Pancreatic CancerRHG61NUFPCELL AND GENE THERAPY

17322IND3-Feb-17ACTIVE3/3/17OTATOCTGTAdvaxis IncLive Attenuated Listeria monocytogenes Expressing Personalized Tumor AntigensLive Attenuated Listeria monocytogenes Expressing Personalized Tumor Antigenstreatment of metastatic cancerCMG81NUFPCELL AND GENE THERAPY

17603IND17-Jul-17ACTIVE8/16/17OTATOCTGTZarour MD, Hassane MPD-1 responder (PD-1 R) derived Fecal Microbiota Transplantation (FMT) + PembrolizumabMultiple products listed for IND 17603PD-1 resistant/ refractory advanced melanomaRH28UFPCELL AND GENE THERAPY

17796IND25-Oct-17HOLD11/22/17HOLD11/22/17OTATOCTGTShapiro MD, Shane AAutologous Adipose-derived Stromal Vascular Fraction (SVF)Autologous, uncultured adipose derived mononuclear cellsAerodigestive FistulaeRH1NUFPCELL AND GENE THERAPY

17660IND11-Aug-17ACTIVE9/7/17OTATOCTGTWilliams MD, David AAutologous CD34+ cells transduced ex vivo with Lentivirus expressing BB694 LCD(-HS4) bGp D12G5 shmiRNo product listed for IND 17660Treatment of autologous CD34+ cells ex vivo for the treatment of Sickle Cell DiseaseRHG11NUFPCELL AND GENE THERAPY

17679IND23-Aug-17ACTIVE9/22/17OTATOCTGTWilliams MD, David AAutologous CD34+ cells transduced ex vivo with the lentiviral vector rHIV-IL2RcoG2SCID (G2SCID)Lentiviral vector clinical batchtreatment of x-linked severe combined immunodeficiency syndromeRHG11NUFPCELL AND GENE THERAPY

17800IND26-Oct-17ACTIVE11/24/17OTATOCTGTCapricor IncAllogeneic Unrelated, Cardiosphere-Derived CellsAllogeneic Cardiopshre-Derived Cells (CDCs)Duchenne Muscular DystrophyCM2S3NORPHAN DESIGNATIONUFPCELL AND GENE THERAPY

17439IND12-Apr-17ACTIVE5/12/17OTATOCTGTTransgene SAPexa-Vec (pexastimogene devacirepvec, JX-594) vaccinia virus engineered to express GM-CSF, and nivolumab, PD-1 receptor blocking antibody.Vaccina/GM-CSF Virus Expressing GM-CSF GeneTreatment of hepatocellular carcinomaCMG51NUFPCELL AND GENE THERAPY

17633IND28-Jul-17ACTIVE7/28/17OTATOCTGTRudnick MD, JeremyAutologous Dendritic Cells Derived from Peripheral Blood Mononuclear Cells, Expanded with Interleukin-4, Granulocyte-Macrophage Colony-Stimulating Factor; Pulsed with Synthetic Tumor-Stem Cell Associated Antigens [AIM-2, MAGE-1, gp100, HER-2, IL-13Ra2] (ICT-107)utologous Dendritic Cells Derived from Peripheral Blood Mononuclear CellsSingle Patient Use - Treatment of glioblastoma in 3 patients.RHEMS4NUFPCELL AND GENE THERAPY

17851IND21-Dec-17PENDING12/21/17OTATOCTGTNational Cancer InstituteMVA-BN-Brachyury, M7824 (MSB001359C), ALT-803, and Epacadostat (INCB024360)Multiple products listed for IND 17851Metastatic Castration Resistant Prostate CancerCMG518UFPCELL AND GENE THERAPY

17764IND6-Nov-17ACTIVE12/6/17OTATOCTGTNational Cancer InstitutePhase 1 Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults with Recurrent and Refractory CD19/CD22-expressing B Cell Malignancies.No product listed for IND 17764Recurrent or refractory, CD19/CD22-expressing, B cell acute lymphoblastic leukemia or lymphomaCMG11NUFPCELL AND GENE THERAPY

17811IND20-Nov-17ACTIVE12/20/17OTATOCTGTNational Cancer InstituteETBX-071 (adenoviral PSA vaccine); ETBX-061 (adenoviral MUC1 vaccine); ETBX-051 (adenoviral brachyury vaccine)No product listed for IND 17811Metastatic Castration Resistant Prostate CancerCMG51NUFPCELL AND GENE THERAPY

17676IND2-Oct-17ACTIVE11/1/17OTATOCTGTNational Cancer InstituteAdenovirus Vector Type 5 Expressing CEA Gene; Adenovirus Vector Type 5 Expressing Muc1 Gene; and Adenovirus Vector Type 5 Expressing Brachyury GeneNo product listed for IND 17676Advanced CancerCMG51NUFPCELL AND GENE THERAPY

17628IND23-Oct-17ACTIVE11/21/17OTATOCTGTNational Cancer InstituteVaccinia Virus Vector (PROSTVAC-V), CV301 (MVA-BN-CV301) and MSB0011359C) Expressing PSA, CEA, MUC-1, LFA-3, B7.1, and ICAM-1Multiple products listed for IND 17628Biochemically Recurrent Prostate CancerCMG526UFPCELL AND GENE THERAPY

17712IND11-Sep-17ACTIVE10/11/17OTATOCTGTInovio Pharmaceuticals IncDNA Plasmid Vectors pGXI 108 (encodes Prostate-specific Membrane Antigen (PSMA)), pGXl404 (encodes Wilms' tumor gene 1 (WT1) antigen)), pGXl434 (encodes Human Telomerase Reverse Transcriptase (hTERT)) and DNA Plasmid Vectors pGX6001 ((IL-12) p35 and p40 subunit proteins))Multiple products listed for IND 17712Treatment of Bladder Cancer (Urothelial Cancer, UCa)CMG618UFPCELL AND GENE THERAPY

17671IND8-Sep-17ACTIVE10/6/17OTATOCTGTInovio Pharmaceuticals IncINO-5401 (DNA plasmids pGX1108, pGX1404, and pGX1434) and INO-9012 (DNA plasmid pGX6001) delivered by electroporation using CELLECTRA 2000 in combination with REGN2810 [Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1)]No product listed for IND 17671Treatment of Glioblastoma (GBM)CMG618UFPCELL AND GENE THERAPY

17666IND31-Aug-17ACTIVE9/29/17OTATOBRRGrifols Therapeutics IncImmune Globulin (Human)Immune Globulin (Human) Serum, IntravenousPassive pre-exposure prophylaxis of HAVCM4NUFPHEMATOLOGICS

17637IND13-Nov-17ACTIVE12/13/17OTATOCTGTReNeuron Group PLCAllogeneic Human Neural Stem Cells (CTX0E03 DP) transduced with a retroviral vector expressing myc with ReNeuron-specific delivery device.Multiple products listed for IND 17637Treatment of patients with stable, moderate or moderately severe residual disability following an ischemic strokeCMG125UFPCELL AND GENE THERAPY

17324IND17-Jan-17ACTIVE2/16/17OTATOCTGTHare MD, Joshua MAllogeneic Umbilical Cord Tissue derived Mesenchymal Stem Cells (UCMSCs) and Bone Marrow derived Human Mesenchymal Stem Cells (BMMSCs)Multiple products listed for IND 17324Cytokine suppression in patients with chronic inflammation due to Metabolic syndrome.RH1S3NUFPCELL AND GENE THERAPY

16897IND31-Jan-17ACTIVE4/11/17HOLD3/2/17OTATOBRRGreen Cross CorpImmune Globulin Intravenous (Human), 10% (GC 5107)No product listed for IND 16897For the treatment of primary humoral deficiency (PHID)CM3NUFPHEMATOLOGICS

17449IND14-Apr-17ACTIVE5/12/17OTATOCTGTCairo MD, Mitchell SViral Specific Cytotoxic T-CellsT-Cells, Allogeneic, Related Donor, EBV-SpecificAdenovrius, Epstein-Barr Virus, CytomegalovirusRH2S3NUFPCELL AND GENE THERAPY

17884IND14-Dec-17ACTIVE12/21/17OTATOCTGTCairo MD, Mitchell SRemestemcel-L, allogeneic Mesenchymal Stromal CellsNo product listed for IND 17884Steroid Refractory Acute GVHD in a single patientRHSPS3NUFPCELL AND GENE THERAPY

17787IND20-Oct-17ACTIVE11/1/17OTATOCTGTCairo MD, Mitchell SAllogeneic, Bone Marrow-Derived, Immuno-Selected, and Ex Vivo Expanded Mesenchymal Precursor Cells, Intravenous Infusion [Rexlemestrocel-L]Allogeneic, Bone Marrow-Derived, Immuno-Selected, and Ex Vivo Expanded Mesenchymal Precursor Cells, Intravenous Infusiontreatment of refractory junctional Epidermis Bullosa in a single patientRHSP1S3NUFPCELL AND GENE THERAPY

17400IND23-Mar-17ACTIVE4/22/17OTATOCTGTBluebird Bio IncAutologous T Lymphocyte-enriched Cells Tranduced with Lentiviral Vector Encoding a Chimeric Antigen Receptor Targeting B Cell Maturation Antigen (anti-BCMA02 CAR); Cultured with a Phosphatidylinositol 3-kinase InhibitorNo product listed for IND 17400Treatment of multiple myeloma and lymphomaCMG11NRARE DISEASEUFPCELL AND GENE THERAPY

17522IND1-Jun-17ACTIVE7/1/17OTATOCTGTBlock MD PhD, Matthew SAutologous Dendritic Cells derived from PBMC pulsed with Prevnar (Pneumococcal 13-valent Conjugate Vaccine [(Diphtheria CRM197 Protein),Pembrolizumab [MK-3475 (anti-PD-1 antibody), [Keytruda], following Cryoablation TherapyAutologous Dendritic Cells derived from PBMCImmunotherapy for metastatic unresectable melanomaRH2S4NUFPCELL AND GENE THERAPY

17815IND7-Nov-17ACTIVE12/7/17OTATOCTGTCenter for Cell and Gene TherapyAutologous Natural Killer T cells transduced with a retroviral vector expressing GD2-specific chimeric antigen receptor and interleukin-15 (GD2.CAR NKT cells)No product listed for IND 17815Relapsed and Refractory NeuroblastomaRHG11NUFPCELL AND GENE THERAPY

17588IND5-Jul-17ACTIVE8/4/17OTATOCTGTCenter for Cell and Gene TherapyTumor-Associated Antigen (TAA)-Specific Cytotoxic T Lymphocytes (CTLs) (TACTOPS)No product listed for IND 17588Treatment of pancreatic cancer patients with metastatic or locally advanced unresectable or resectable diseaseRH1S4NUFPCELL AND GENE THERAPY

17586IND5-Jul-17ACTIVE8/4/17OTATOCTGTCenter for Cell and Gene TherapyTumor-Associated Antigen (TAA)-Specific Cytotoxic T Lymphocytes (CTLs)No product listed for IND 17586Treatment of breast cancer patients with metastatic or locally recurrent unresectable disease as measured by clinical benefit rate according to RECIST criteriaRH1S4NUFPCELL AND GENE THERAPY

17461IND25-Apr-17ACTIVE5/25/17OTATOCTGTCenter for Cell and Gene TherapyAutologous T-Cells Transduced with Retroviral Vectors Expressing a second Generation Chimeric Antigen Receptor CD5.CARNo product listed for IND 17461Relapsed/refractory CD5+ T cell malignanciesRH1S3NUFPCELL AND GENE THERAPY

17391IND20-Mar-17ACTIVE4/19/17OTATOBRRCSL Behring LLCC1 Esterase Inhibitor (Human)C1 Esterase Inhibitor, HumanChronic treatment of refractory antibody mediated rejection (AMR) in adult kidney transplant recipients in combination with i.v. immunoglobulin containing regimensCM3NRARE DISEASEUFPCELL AND GENE THERAPY

17335IND1-Feb-17ACTIVE3/3/17OTATOCTGTBorrello MD, IvanLenalidomide with or without Allogeneic Myeloma GM-CSF Vaccine (Irradiated H929, U266 and K562/GM-CSF cells)Multiple products listed for IND 17335Treatment of Multiple MyelomaRH2S4NUFPCELL AND GENE THERAPY

17414IDE3-Mar-17REFUSE TO ACCEPT3/28/17OTATOCTGTTissue Genesis LLCCell Isolation SystemFat (Adipose) TissuesTreatment of the Symptoms of Erectile DysfunctionCM1NUFMDEVICES

17589IND6-Jul-17WITHDRAWN10/4/17OTATOCTGTThe Methodist Hospital Research InstituteAutologous adipose-derived mesenchymal stem cellsAutologous adipose-derived mesenchymal stem cellsTreatment of Autoimmune Thromocytopenia Purpura and Hemolytic Uremic Syndrome in a Single PatientRHSPS3NUFPCELL AND GENE THERAPY

17690IND28-Aug-17ACTIVE9/27/17OTATOCTGTChilds MD, Richard WAutologous enriched T cells (CD8+/CD34+) Transduced with Retroviral Vector (HERV-E TCR CD34t 7G1) Expressing HERV-E T cell Receptor GeneNo product listed for IND 17690Clear cell Renal Cell CarcinomaRHG4NUFPCELL AND GENE THERAPY

17348IND7-Feb-17ACTIVE3/9/17OTATOCTGTChilds MD, Richard WAllogeneic Cord Blood-derived Ex Vivo Expanded with or without Allogeneic Haploidentical Donor Co-transplantationMultiple products listed for IND 17348Severe Aplastic Anemia (SAA) and Myelodysplastic Syndrome (MDS)RH2S3NUFPCELL AND GENE THERAPY

17685IND25-Aug-17ACTIVE9/14/17OTATOCTGTBota MD PhD, Daniela AAutologous Dendritic Cells Derived from Peripheral Blood Mononuclear Cells, Expanded with Interleukin-4, Granulocyte-Macrophage Colony-Stimulating Factor; Pulsed with Synthetic Tumor-Stem Cell Associated Antigens [AIM-2, MAGE-1, gp100, HER-2, IL-13Ra2] (ICT-107)Autologous Dendritic Cells Derived from Peripheral Blood Mononuclear CellsSINGLE PATIENT USE: Treatment for GlioblastomaRHSPS4NUFPCELL AND GENE THERAPY

17504IND1-Jun-17ACTIVE6/30/17OTATOCTGTGovindan MD, RamaswamyPilot Feasibility Study of the Combination of a Personalized Therapeutic Anti-tumor Vaccine with PembrolizumabMultiple products listed for IND 17504Non-Small Cell Lung CancerRH1NUFPCELL AND GENE THERAPY

17748IND1-Dec-17ACTIVE12/29/17OTATOCTGTJuno Therapeutics IncAutologous CD4+ and CD8+ T Cells (JCARH125) Transduced with Replication-Incompetent, Self-Inactivating (SIN) Lentiviral Vector(v20008) encoding Chimeric Antigen Receptor (CAR-T) and B-Cell Maturation Antigen (BCMA)Autologous CD4+ and CD8+ T cells Transduced with Self-Inactivating (SIN) Lentiviral Vector (v20008) Expressing CD19-specific Chimeric Antigen Receptor (CAR) (JCAR0125)Immunotherapy for relapsed or refractory multiple myelomaCMG11NORPHAN DESIGNATIONUFPCELL AND GENE THERAPY

17444IND12-Apr-17ACTIVE5/12/17OTATOCTGTMueller MD PhD, SabineModified Measles virus MV-NISHuman Thyroidal Sodium-Iodide Symporter Gene (Measles Virus Vector) MV-NISMultiply recurrent medulloblastoma single patient expanded accessRHSPG5NUFPCELL AND GENE THERAPY

17678IND23-Aug-17ACTIVE12/13/17HOLD9/22/17OTATOCTGTBleakley MD PhD, MarieAllogenic CD8+ and CD4+ Memory T Cells Transduced with a Lentiviral Vector (LV; pRRLSIN) Containing iC9-HA1 TCR2-RQR-CD8 transgene to Express an HA-1-Specific T cell ReceptorMultiple products listed for IND 17678Patients with persistent or recurrent acute leukemia undergoing or following HCTRHG41NUFPCELL AND GENE THERAPY

17576IND28-Jun-17ACTIVE6/28/17OTATOCTGTLevy MD PhD, Michael LAllogeneic-Unrelated Bone Marrow Derived Mesenchymal Stem CellsNo product listed for IND 17576Emergency - Treatment of COPDEM

17584IND3-Jul-17ACTIVE12/15/17HOLD8/2/17OTATOCTGTWake Forest Institute for Regenerative MedicineAutologous corporal smooth muscle cells (SMC) and endothelia cells(EC) seeded on decellularized corpora cavernose.Multiple products listed for IND 17584Repair or replace irreversibly damaged penile corporaRH1S5NUFPCELL AND GENE THERAPY

17583IND3-Jul-17HOLD8/2/17HOLD8/2/17OTATOCTGTWake Forest Institute for Regenerative MedicineAutologous Urothelial Cells (UC) and Smooth Muscle Cells (SMC) Seeded on a Polyglycolic Acid (PGA) Bladder Shaped ScaffoldMultiple products listed for IND 17583Subjects with Fibrotic Contracted BladderRH2S55UFPCELL AND GENE THERAPY

17562IND22-Jun-17ACTIVE9/20/17HOLD7/21/17OTATOCTGTBollard MD, CatherineAutologous ex vivo expanded HIV-1 specific T-cells (HST-NEETs)No product listed for IND 17562Therapy in HIV-infected individuals suppressed on antiretroviral therapy (ART)RH1S3NUFPCELL AND GENE THERAPY

17762IND5-Oct-17ACTIVE10/11/17OTATOCTGTKiromic IncAutologous Dendritic Cells Derived from Peripheral Blood Mononuclear Cells, Cultured with Interleukin-4, Granulocyte-Macrophage Colony-Stimulating Factor, Tumor Necrosis Factor-alpha, Interleukin-1beta, Pulsed with Tumor Antigens and Followed by Low Dose Interleukin-2Multiple products listed for IND 17762Hematological malignanciesCM1NUFPCELL AND GENE THERAPY

17669IND25-Aug-17ACTIVE9/24/17OTATOBRRCambium Medical Technologies LLCFibrinogen-Depleted Human Platelet LysateMultiple products listed for IND 17669Dry Eye Secondary to Graft vs. Host DiseaseCM1NUFPHEMATOLOGICS

17482IND5-May-17EXEMPT5/16/17OTATOCTGTRamsingh MD, GiridharanHLA-mismatched allogeneic cellular therapy (Microtransplantation)No product listed for IND 17482Intermediate-Risk Acute Myeloid Leukemia

Gene Therapy: Scientific Advances• Human Genome Project

• Completed in October 2003• 99% of human genes sequenced to 99% accuracy

• Development of new vectors• Adeno-associated virus (AAV)• Lentivirus

• Genome editing

www.fda.gov

CAR T Cells: A Novel Way to Treat Cancer

Shannon L. Maude et al. Blood 2015CTL, cytotoxic T lymphocyte; MHC, major histocompatibility complex

www.fda.gov

Gene Therapy United States Marketing Approvals in 2017 • Kymriah (tisagenlecleucel; Novartis)

• CAR T cells (target – CD19)• Refractory childhood lymphoblastic B cell leukemia

• Yescarta (axicabtagene ciloleucel; Gilead (Kite))• CAR T cells (target – CD19)• Adult patients with relapsed or refractory large B cell

lymphoma

• Luxturna (voretigene neparvovec-rzyl; Spark Therapeutics)

• Gene therapy (adeno-associated virus vector)• Biallelic RPE65 mutation-associated retinal dystrophy

www.fda.gov

www.fda.gov

Baseball

www.fda.gov

Clinical TrialsPreclinical Marketing Application Post-marketing

BLAPhase 3Phase 2Phase 1PreclinicalDevelopment Post marketing

Drug Development

www.fda.gov

Lou Gehrig

Hank AaronBabe Ruth

Gene Therapies for Rare Diseases

FDA Draft Guidance (July 2018): Human Gene Therapy for Rare Disease

… consider designing … first-in-human study to be an adequate and well-controlled investigation that has the potential … to provide evidence of effectiveness to support a marketing application.

www.fda.gov

Efficient Development of Gene Therapies

1) Teamwork

Requires collaboration of scientists, academic investigators, sponsors (e.g., pharmaceutical industry), funding organizations, patients, patient

advocacy groups, and regulatory agencies

www.fda.gov

Efficient Development of Gene Therapies

2) Preparation

• Design and conduct Natural History studies that will support subsequent drug development

• When preclinical studies are beginning, draft the design of the clinical study(ies)

• Resolve manufacturing issues, as much as possible, before first-in-human clinical trial

www.fda.gov

Efficient Development of Gene Therapies

3) Try to hit a home run!

Design first-in-human clinical trial to provide evidence of effectiveness (e.g., include randomized controls)

www.fda.gov

Contact Information

• Regulatory Questions:

OTAT Main Line – 240 402 8190

Email: OTATRPMS@fda.hhs.gov and

Lori.Tull@fda.hhs.gov

• OTAT Learn Webinar Series:

http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/ucm232821.htm

• CBER website: www.fda.gov/BiologicsBloodVaccines/default.htm

• Phone: 1-800-835-4709 or 240-402-8010

• Consumer Affairs Branch: ocod@fda.hhs.gov

• Manufacturers Assistance and Technical Training Branch: industry.biologics@fda.hhs.gov

• Follow us on Twitter: https://www.twitter.com/fdacber

FDA Headquarters

www.fda.gov

mailto:OTATRPMS@fda.hhs.govmailto:Lori.Tull@fda.hhs.govhttp://www.fda.gov/BiologicsBloodVaccines/NewsEvents/ucm232821.htmhttp://www.fda.gov/BiologicsBloodVaccines/default.htmmailto:ocod@fda.hhs.govmailto:industry.biologics@fda.govhttps://www.twitter.com/fdacber

Acknowledgements

• Rachael Anatol, PhD• Kimberly Benton, PhD• Larissa Lapteva, MD, MHS

www.fda.gov

Wilson W. Bryan, M.D.wilson.bryan@fda.hhs.gov

www.fda.gov

mailto:wilson.bryan@fda.hhs.gov

Gene Therapy: Efficient Drug Development

Drug development is like baseball:1) Preparation2) Teamwork3) The heroes try for the home run!

www.fda.gov

Baseball

www.fda.gov

Clinical TrialsPreclinical Marketing Application Post-marketing

BLAPhase 3Phase 2Phase 1PreclinicalDevelopment Post marketing

Drug Development

Gene Therapies for Rare Diseases

September 13, 2018

Rare Disease Scientific WorkshopEverylife Foundation for Rare Diseases

Washington, DC

Wilson W. BryanOffice of Tissues and Advanced Therapies (OTAT)

Center for Biologics Evaluation and Research (CBER)United States Food and Drug Administration (US FDA)

Gene Therapies �for Rare DiseasesCenter for Biologics Evaluation and Research�(CBER)Cell and Gene Therapy�Investigational New Drug Applications Investigational New Drug Applications (INDs) �for Gene Therapy Products, �2002-2017�Gene Therapy: Scientific AdvancesCAR T Cells: A Novel Way to Treat Cancer��Gene Therapy �United States Marketing Approvals in 2017 Slide Number 8BaseballSlide Number 10Gene Therapies for Rare DiseasesEfficient Development of Gene TherapiesEfficient Development of Gene TherapiesEfficient Development of Gene TherapiesContact InformationAcknowledgementsSlide Number 17Gene Therapy: �Efficient Drug DevelopmentBaseballGene Therapies �for Rare Diseases