DOCSLIB.ORG

Kymriah, INN-Tisagenlecleucel

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Kymriah, INN-Tisagenlecleucel 28 June 2018 EMA/485563/2018 Committee for Medicinal Products for Human Use (CHMP) Assessment report Kymriah International non-proprietary name: tisagenlecleucel Procedure No. EMEA/H/C/004090/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. Administrative information Name of the medicinal product: Kymriah Applicant: Novartis Europharm Limited Vista Building Elm Park, Merrion Road Dublin 4 Ireland Active substance: tisagenlecleucel International Non-proprietary Name/Common tisagenlecleucel Name: Pharmaco-therapeutic group other antineoplastic agents (ATC Code): (Not yet assigned) Indicated for the treatment of: Therapeutic indications: Paediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse. Adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. Pharmaceutical form: dispersion for infusion Strength: 1.2 x 106 – 6 x 108 cells Route of administration: intravenous use Packaging: bag (ethylene vinyl acetate) Package size: 1-3 bags Assessment report EMA/CHMP/443047/2018 Page 2 Table of contents 1.45T Background information on the procedure 45T .............................................. 8 1.1.45T Submission of the dossier45T ...................................................................................... 8 1.2.45T Steps taken for the assessment of the product 45T ....................................................... 10 2.45T Scientific discussion 45T .............................................................................. 12 2.1.45T Problem statement 45T ............................................................................................. 12 2.1.1.45T Disease or condition 45T ......................................................................................... 12 2.1.2.45T Epidemiology and risk factors, screening tools/prevention 45T .................................... 12 2.1.3.45T Biologic features Aetiology and pathogenesis 45T ...................................................... 13 2.1.4.45T Clinical presentation, diagnosis and stage/prognosis 45T ............................................ 13 2.1.5.45T Management 45T ................................................................................................... 14 2.2.45T Quality aspects45T .................................................................................................. 17 2.2.1.45T Introduction 45T .................................................................................................... 17 2.2.2.45T Active Substance45T ............................................................................................. 17 2.2.3.45T Finished Medicinal Product45T ................................................................................ 25 2.2.4.45T Discussion and conclusions on chemical, pharmaceutical and biological aspects 45T ....... 27 2.2.5.45T Recommendations for future quality development 45T ............................................... 28 2.3.45T Non-clinical aspects 45T ............................................................................................ 28 2.3.1.45T Introduction 45T .................................................................................................... 28 2.3.2.45T Pharmacology45T ................................................................................................. 28 2.3.3.45T Pharmacokinetics................................45T ............................................................. 31 2.3.4.45T Toxicology 45T ...................................................................................................... 32 2.3.5.45T Ecotoxicity/environmental risk assessment 45T ......................................................... 37 2.3.6.45T Discussion on the non-clinical aspects45T ................................................................ 39 2.3.7.45T Conclusion on the non-clinical aspects45T ................................................................ 41 2.4.45T Clinical aspects45T .................................................................................................. 41 2.4.1.45T Introduction 45T .................................................................................................... 41 2.4.2.45T Pharmacokinetics................................45T ............................................................. 42 2.4.3.45T Pharmacodynamics45T .......................................................................................... 47 2.4.4.45T Discussion on clinical pharmacology 45T ................................................................... 57 2.4.5.45T Conclusions on clinical pharmacology 45T ................................................................. 58 2.5.45T Clinical efficacy45T .................................................................................................. 58 2.5.1.45T Dose response studies................................45T ...................................................... 58 2.5.2.45T Main studies 45T ................................................................................................... 59 2.5.3.45T Discussion on clinical efficacy 45T .......................................................................... 117 2.5.4.45T Conclusions on the clinical efficacy 45T ................................................................... 128 2.6.45T Clinical safety45T .................................................................................................. 129 2.6.1.45T Discussion on clinical safety 45T ............................................................................ 161 2.6.2.45T Conclusions on the clinical safety45T ..................................................................... 168 2.7.45T Risk Management Plan 45T ...................................................................................... 168 2.8.45T Pharmacovigilance45T ............................................................................................ 178 Assessment report EMA/CHMP/443047/2018 Page 3 2.9.45T New Active Substance45T ....................................................................................... 178 2.10.45T Product information 45T ........................................................................................ 178 2.10.1.45T User consultation 45T ......................................................................................... 178 2.10.2.45T Additional monitoring 45T ................................................................................... 178 3.45T Benefit-Risk Balance................................45T ............................................ 179 3.1.45T Therapeutic Context 45T ......................................................................................... 179 3.1.1.45T Disease or condition 45T ....................................................................................... 179 3.1.2.45T Available therapies and unmet medical need 45T ..................................................... 179 3.1.3.45T Main clinical studies45T ....................................................................................... 180 3.2.45T Favourable effects45T ............................................................................................ 180 3.3.45T Uncertainties and limitations about favourable effects 45T ........................................... 181 3.4.45T Unfavourable effects 45T ......................................................................................... 181 3.5.45T Uncertainties and limitations about unfavourable effects 45T ....................................... 182 3.6.45T Effects Table45T .................................................................................................... 182 3.7.45T Benefit-risk assessment and discussion 45T ............................................................... 184 3.7.1.45T Importance of favourable and unfavourable effects 45T ............................................ 184 3.7.2.45T Balance of benefits and risks45T ........................................................................... 185 3.7.3.45T Additional considerations on the benefit-risk balance 45T ......................................... 185 3.8.45T Conclusions 45T ..................................................................................................... 185 4.45T Recommendations 45T ............................................................................... 186 Assessment report EMA/CHMP/443047/2018 Page 4 List of abbreviations Abbreviation Definition AE Adverse event AESI Adverse event of special interest ADR Adverse drug reaction ALL Acute lymphoblastic leukemia ALT Alanine aminotransferase AST Aspartate aminotransferase AUC Area under curve AUC0-28d AUC from time zero to Day 28, in peripheral blood (% or copies/µg DNA x days) AUC0-84d AUC from time zero to Day 84, in peripheral blood (% or copies/µg DNA x days) BOR Best overall response BSA Bovine serum albumin CAR Chimeric antigen receptor CD Cluster of differentiation CF Cell factory CHMP Committee for Medicinal
Load more

Recommended publications
  • Catalyzing Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy
    Current Hematologic Malignancy Reports (2019) 14:47–55 https://doi.org/10.1007/s11899-019-0498-6 STEM CELL TRANSPLANTATION (R MAZIARZ, SECTION EDITOR) Industry’s Giant Leap Into Cellular Therapy: Catalyzing Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy Stacie Ittershagen1 & Solveig Ericson1 & Lamis Eldjerou1 & Ali Shojaee1 & Eric Bleickardt1 & Manisha Patel1 & Tetiana Taran1 & Oezlem Anak2 & Charlene Hall1 & Mimi Leung1 & Deborah Roccoberton1 & Florence Salmon2 & Miriam Fuchs2 & Vadim Romanov1 & David Lebwohl1 Published online: 21 January 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of Review We describe the significant technological leap from bench to bedside that was achieved through a strong academic-industry collaboration between dedicated clinicians and researchers at the University of Pennsylvania, the Children’s Hospital of Philadelphia, and Novartis to commercialize the chimeric antigen receptor T cell (CAR-T) therapy tisagenlecleucel (CTL019; Kymriah®; Novartis Pharma AG, Basel, Switzerland). Recent Findings Tisagenlecleucel was the first CAR-T therapy and the first gene therapy to receive US Food and Drug Administration approval in 2017, with an initial indication for pediatric and young adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia, followed by approval in May 2018 for a second indication in adult patients with r/r diffuse large B cell lymphoma. Subsequent approvals in the European Union, Switzerland, and Canada soon followed. Summary The tisagenlecleucel success story represents the development and commercialization of a first-of-its-kind personal- ized cellular therapy with a manufacturing process that supports commercial production and ongoing global clinical trials in a growing number of countries. Keywords Acute lymphoblastic leukemia (ALL) .
    [Show full text]
  • Oncologic Drugs Advisory Committee Briefing Document
    Tisagenlecleucel (CTL019) FDA Advisory Committee Briefing Document Novartis 12-Jul-2017 ONCOLOGIC DRUGS ADVISORY COMMITTEE BRIEFING DOCUMENT Tisagenlecleucel (CTL019) for the TREATMENT OF PEDIATRIC AND YOUNG ADULT PATIENTS WITH RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA AVAILABLE FOR PUBLIC DISCLOSURE WITHOUT REDACTION Page 1 Tisagenlecleucel (CTL019) FDA Advisory Committee Briefing Document Novartis 12-Jul-2017 Table of contents Table of contents .................................................................................................................2 List of tables ........................................................................................................................4 List of figures ......................................................................................................................6 List of abbreviations ............................................................................................................8 1 Executive summary ...........................................................................................................10 1.1 Tisagenlecleucel (CTL019) ...................................................................................10 1.1.1 Targeted indication................................................................................10 1.1.2 Unmet medical need for r/r B-cell ALL................................................10 1.1.3 Mechanism of action.............................................................................11 1.1.4 Manufacturing process
    [Show full text]
  • Cancer Immunotherapy Comes of Age and Looks for Maturity ✉ Amanda Finck1, Saar I
    COMMENT https://doi.org/10.1038/s41467-020-17140-5 OPEN Cancer immunotherapy comes of age and looks for maturity ✉ Amanda Finck1, Saar I. Gill1 & Carl H. June 1,2 As Nature Communications celebrates a 10-year anniversary, the field has witnessed the transition of cancer immunotherapy from a pipe dream to an established powerful cancer treatment modality. Here we discuss the opportu- 1234567890():,; nities and challenges for the future. Improving the natural immune system through immune checkpoint blockade interference Advances in the understanding of basic immunology have ushered in two major approaches for cancer therapy over the past 10 years. The first is checkpoint therapy to augment the function of the natural immune system. The second uses the emerging discipline of synthetic biology and the tools of molecular biology and genome engineering to create new forms of biological structures, engineered viruses and cells with enhanced functionalities (Fig. 1). Trastuzumab, the monoclonal antibody targeting HER2, was the first recombinant antibody to be commercially approved, in 1997. However, over the past 10 years, a paradigm shift in cancer therapy occurred with the addition of inhibitors of the immune checkpoint blockade (ICB), CTLA-4 and PD-1, to the clinics. The first to be approved was the anti-CTLA-4 inhibitor ipilimumab for metastatic melanoma in 2011. More than a dozen types of cancer are now treated with ICBs. Perhaps most surprising to the field is that lung cancer can now be treated with PD-1 (CD279) and CTLA-4 (CD152) antagonists as a component of first line therapy. 10 years ago, the consensus among thoracic oncologists was that the solution for lung cancer was inhibitors of oncogene-driven signaling pathways and the field had dismissed the notion that lung cancer would be an immunologically responsive tumor.
    [Show full text]
  • Lentiviral Vectors for T Cell Engineering: Clinical Applications, Bioprocessing and Future Perspectives
    viruses Review Lentiviral Vectors for T Cell Engineering: Clinical Applications, Bioprocessing and Future Perspectives Roman P. Labbé 1,2,*, Sandrine Vessillier 2 and Qasim A. Rafiq 1 1 Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Gower Street, London WC1E 6BT, UK; q.rafi[email protected] 2 Division of Biotherapeutics, National Institute for Biological Standards and Control (NIBSC), Blanche Lane, Potters Bar, South Mimms EN6 3QG, UK; [email protected] * Correspondence: [email protected] Abstract: Lentiviral vectors have played a critical role in the emergence of gene-modified cell thera- pies, specifically T cell therapies. Tisagenlecleucel (Kymriah), axicabtagene ciloleucel (Yescarta) and most recently brexucabtagene autoleucel (Tecartus) are examples of T cell therapies which are now commercially available for distribution after successfully obtaining EMA and FDA approval for the treatment of blood cancers. All three therapies rely on retroviral vectors to transduce the therapeutic chimeric antigen receptor (CAR) into T lymphocytes. Although these innovations represent promis- ing new therapeutic avenues, major obstacles remain in making them readily available tools for medical care. This article reviews the biological principles as well as the bioprocessing of lentiviral (LV) vectors and adoptive T cell therapy. Clinical and engineering successes, shortcomings and future opportunities are also discussed. The development of Good Manufacturing Practice (GMP)- compliant instruments, technologies and protocols will play an essential role in the development of LV-engineered T cell therapies. Citation: Labbé, R.P.; Vessillier, S.; Rafiq, Q.A. Lentiviral Vectors for T Keywords: CAR; T cell; lentivirus; viral vector; bioprocessing; manufacture Cell Engineering: Clinical Applications, Bioprocessing and Future Perspectives.
    [Show full text]
  • Tisagenlecleucel for Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma: Clinical Report
    CADTH OPTIMAL USE REPORT Tisagenlecleucel for Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma: Clinical Report PROSPERO REGISTRATION NUMBER: CRD42018103201 Service Line: Optimal Use Version: Volume 8, Issue 3c Publication Date: January 2019 Report Length: 158 Pages Cite As: Tisagenlecleucel for Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma: Clinical Report. Ottawa: CADTH; 2019 Jan. (CADTH optimal use report; vol.8, no.3c). ISSN: 1927-0127 (English only) Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document.
    [Show full text]
  • KYMRIAH Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Administer 0.6 to 6.0 x 108 CAR-positive viable T cells These highlights do not include all the information needed to use intravenously. (2.2) KYMRIAH safely and effectively. See full prescribing information for KYMRIAH. ---------------------DOSAGE FORMS AND STRENGTHS--------------------- ® • Pediatric and Young Adult B-cell ALL (up to 25 years of age) KYMRIAH (tisagenlecleucel) suspension for intravenous infusion 6 Initial U.S. Approval: 2017 A single dose of KYMRIAH contains 0.2 to 5.0 x 10 CAR-positive viable T cells per kg of body weight for patients 50 kg or less, or 0.1 to 2.5 x 108 CAR- WARNING: CYTOKINE RELEASE SYNDROME and positive viable T cells for patients more than 50 kg, suspended in one to three NEUROLOGICAL TOXICITIES patient-specific infusion bag(s) for IV infusion. (3) See full prescribing information for complete boxed warning. • Adult Relapsed or Refractory Diffuse Large B-cell Lymphoma A single dose of KYMRIAH contains 0.6 to 6.0 x 108 CAR-positive viable T • Cytokine Release Syndrome (CRS), including fatal or life-threatening cells suspended in one to three patient-specific infusion bag(s) for IV infusion. reactions, occurred in patients receiving KYMRIAH. Do not (3) administer KYMRIAH to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with -------------------------------CONTRAINDICATIONS----------------------------- tocilizumab or tocilizumab and corticosteroids. (2.3, 2.4, 5.1) None. (4) • Neurological toxicities, which may be severe or life-threatening, can ------------------------WARNINGS AND PRECAUTIONS----------------------- occur following treatment with KYMRIAH, including concurrently • Hypersensitivity Reactions: Monitor for hypersensitivity reactions during with CRS.
    [Show full text]
  • Kymriah (Tisagenlecleucel)
    Kymriah (tisagenlecleucel) Policy Number: Current Effective Date: MM.02.036 August 1, 2019 Lines of Business: Original Effective Date: HMO; PPO; QUEST Integration June 1, 2018 Precertification: Place(s) of Service: Required, see section IV Inpatient I. Description The spontaneous regression of certain cancers (e.g., renal cell carcinoma, melanoma) supports the idea that a patient’s immune system can delay tumor progression and, on rare occasions, can eliminate tumors altogether. These observations have led to research into various immunologic therapies designed to stimulate a patient’s own immune system. Adoptive immunotherapy is a method of activating lymphocytes and/or other types of cells for the treatment of cancer and other diseases. Cells are removed from the patient, processed for some period of time, and then infused back into the patient. Tisagenlecleucel For individuals who are 3 to 25 years of age with relapsed or refractory B-cell acute lymphoblastic leukemia who receive tisagenlecleucel, the evidence includes multiple single-arm prospective trials. Relevant outcomes are overall survival, disease-specific survival, quality of life, and treatment-related mortality and morbidity. The pivotal single-arm trials reported an 83% response rate (measured by complete response or complete remission with incomplete blood count) in heavily pretreated patients. All patients who achieved a complete remission or complete remission with incomplete blood count were also minimal residual disease- negative, which is predictive of survival in acute lymphoblastic leukemia patients. After a median follow-up of 4.8 months, the median duration of response was not reached. The observed benefits seen with tisagenlecleucel were offset by a high frequency and severity of adverse reactions.
    [Show full text]
  • The Cytokine Release Syndrome and Associated Arrhythmias
    Review Cardiovascular Complications of Chimeric Antigen Receptor T-Cell Therapy: The Cytokine Release Syndrome and Associated Arrhythmias Cesar Simbaqueba Clavijo1, Maria Patarroyo Aponte2, Peter Kim3, Anita Deswal3, Nicolas L. Palaskas3, Cezar Downloaded from http://meridian.allenpress.com/innovationsjournals-JIPO/article-pdf/doi/10.36401/JIPO-20-10/2552894/10.36401_jipo-20-10.pdf by University of California user on 02 August 2020 Iliescu3, Eiman Jahangir4, Eric H. Yang5, Raphael E. Steiner6, Juan Lopez-Mattei3 1Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 2Department of Cardiology, University of Texas Health System, Memorial Hermann Hospital, Houston, Texas 3Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, Texas 4Department of Cardiology, Vanderbilt University Medical Center, Vanderbilt, Tennessee 5UCLA Cardio-Oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 6Department of Lymphoma-Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas Address correspondence to Juan Lopez-Mattei, MD ([email protected]) Source of Support: None. Conflict of Interest: None. Received: March 24, 2020; Accepted: May 28, 2020 Simbaqueba Clavijo CS, Aponte MP, Kim, P, Deswal A, Palaskas NL, Iliescu C, Jahangir E, Yang, EH, Steiner RE, Lopez-Mattei J. Cardiovascular complications of chimeric antigen receptor T-cell therapy: the cytokine release syndrome and associated arrhythmias. J Immunother Precis Oncol. 2020; 3:000–000. DOI: 10.36401/JIPO-20-10. & Innovative Healthcare Institute ABSTRACT In recent years, cancer treatment has evolved, and new therapies have been introduced with significant improvement in prognosis. The immunotherapies stand out owing to their efficacy and remission rate.
    [Show full text]
  • Kymriah (Tisagenlecleucel) (Intravenous) Document Number: IC-0319 Last Review Date: 10/30/2018 Date of Origin: 09/19/2017 Dates Reviewed: 09/2017, 06/2018, 11/2018
    Kymriah (tisagenlecleucel) (Intravenous) Document Number: IC-0319 Last Review Date: 10/30/2018 Date of Origin: 09/19/2017 Dates Reviewed: 09/2017, 06/2018, 11/2018 I. Length of Authorization Coverage will be provided for one treatment course (1 dose of Kymriah) and may not be renewed. II. Dosing Limits A. Quantity Limit (max daily dose) [Pharmacy Benefit]: N/A B. Max Units (per dose and over time) [Medical Benefit]: B-Cell Precursor Acute Lymphoblastic Leukemia (ALL) 1 billable unit (1 infusion of up to 250 million car-positive viable t-cells) Large B-Cell Lymphoma 1 billable unit (1 infusion of up to 600 million car-positive viable t-cells) III. Initial Approval Criteria Coverage is provided in the following conditions: Patient does not have an active infection or inflammatory disorder; AND Patient has not received live vaccines within 6 weeks prior to the start of lymphodepleting chemotherapy and will not receive live vaccines until immune recovery following Kymriah treatment; AND Patient has been screened for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines prior to collection of cells (leukapheresis); AND Prophylaxis for infection has been followed according to local guidelines; AND Healthcare facility has enrolled in the Kymriah REMS and training has been given to providers on the management of cytokine release syndrome (CRS) and neurological toxicities; AND Proprietary & Confidential © 2018 Magellan Health, Inc. Patient has not received prior
    [Show full text]
  • Kymriah Chimeric Antigen Receptor T Cell Therapy
    Subject: Chimeric Antigen Receptor T cell Therapy (CAR-T Cell Therapy): Original Effective Kymriah (Tisagenlecleucel) Date: 4/12/2018 Molina Clinical Policy (MCP) Number: Revision Date(s): 3/11/2019 MCP-317a Review Date: 3/11/2019 MCPC Approval Date: 3/11/2019 DISCLAIMER This Molina clinical policy is intended to facilitate the Utilization Management process. It expresses Molina's determination as to whether certain services or supplies are medically necessary, experimental, investigational, or cosmetic for purposes of determining appropriateness of payment. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered (i.e., will be paid for by Molina) for a particular member. The member's benefit plan determines coverage. Each benefit plan defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need to consult the member's benefit plan to determine if there are any exclusion(s) or other benefit limitations applicable to this service or supply. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the CMS website . The coverage directive(s) and criteria from an existing National Coverage Determination (NCD) or Local Coverage Determination (LCD) will supersede the contents of this Molina clinical policy document and provide the directive for all Medicare members.
    [Show full text]
  • BLA 125646 Tisagenlecleucel 1 FDA Briefing Document Oncologic Drugs
    BLA 125646 Tisagenlecleucel FDA Briefing Document Oncologic Drugs Advisory Committee Meeting BLA 125646 Tisagenlecleucel Novartis Pharmaceuticals Corporation DISCLAIMER STATEMENT The attached package contains background information prepared by the Food and Drug Administration (FDA) for the panel members of the advisory committee. The FDA background package often contains assessments and/or conclusions and recommendations written by individual FDA reviewers. Such conclusions and recommendations do not necessarily represent the final position of the individual reviewers, nor do they necessarily represent the final position of the Review Division or Office. We bring the BLA for tisagenlecleucel, a first- in-class product, with the applicant's proposed indications to this Advisory Committee to gain the Committee’s insights and opinions. The background package may not include all issues relevant to the final regulatory recommendation and instead is intended to focus on issues identified by the Agency for discussion by the advisory committee. The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized. The final determination may be affected by issues not discussed at the advisory committee meeting. 1 BLA 125646 Tisagenlecleucel Table of Contents 1. PROPOSED INDICATION.................................................................................................. 8 2. EXECUTIVE SUMMARY ..................................................................................................
    [Show full text]
  • Tisagenlecleucel for Treating Relapsed Or Refractory Diffuse Large B-Cell Lymphoma After 2 Or More Systemic Therapies
    Tisagenlecleucel for treating relapsed or refractory diffuse large B-cell lymphoma after 2 or more systemic therapies Technology appraisal guidance Published: 13 March 2019 www.nice.org.uk/guidance/ta567 © NICE 2020. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and-conditions#notice-of- rights). Tisagenlecleucel for treating relapsed or refractory diffuse large B-cell lymphoma after 2 or more systemic therapies (TA567) Your responsibility The recommendations in this guidance represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, health professionals are expected to take this guidance fully into account, alongside the individual needs, preferences and values of their patients. The application of the recommendations in this guidance are at the discretion of health professionals and their individual patients and do not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian. Commissioners and/or providers have a responsibility to provide the funding required to enable the guidance to be applied when individual health professionals and their patients wish to use it, in accordance with the NHS Constitution. They should do so in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Commissioners and providers have a responsibility to promote an environmentally sustainable health and care system and should assess and reduce the environmental impact of implementing NICE recommendations wherever possible.
    [Show full text]