Journal Archive

Commercial Insights

Cell & Gene Therapy Commercial Insight – March 2017

Mark Curtis & Richard Philipson

Providing a critical overview of the sector’s commercial developments – M&As, licensing agreements & collaborations, financial results, IPOs and clinical/regulatory updates, with commentary from our Expert Contributors.

CELL THERAPY:

It was a rollercoaster of a month for the CAR-T industry. At its low Juno announced the discontinuation of its lead product JCAR015, a decision which, following a series of patient deaths and the halt of its Phase 2 ROCKET study in 2016, is not entirely surprising. Juno will now focus on JCAR017, a product with a defined T cell composition, and one it feels has better prospects for approval overall. While potential safety issues with CAR-T products have always been acknowledged, the news will test investor resilience. At its peak, later in the month, Kite Pharma announced completion of submission of its US Biologics License Application for axicabtagene ciloleucel in patients with relapsed or refractory aggressive NHL. Now we play the waiting game, for the approval of the world’s first CAR-T product.

GENE THERAPY:

Gene therapy is an approach that seems naturally suited to developing treatments for rare, monogenic diseases. This month sees progress for a much more prevalent condition – Alzheimer’s disease – with encouraging preclinical data released by Sangamo Therapeutics using its ZFP technology. Another interesting announcement comes from Lysogene, which released baseline data from its observational study in MPS IIIA. Regulators have recently made clear their desire to see companies operating in rare diseases provide data on the natural history of the condition under study – Lysogene is clearly fulfilling the wishes of regulators in this regard. Not a month goes by without an announcement from bluebird bio, and this month is no different, with the announcement of positive data from the first patient treated with its lentiviral vector for severe sickle cell disease.

DOI: 10.18609/cgti.2017.025
Citation: Cell Gene Therapy Insights 2017; 3(4), 211-226.

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Expert Insight

Toward an integrated model of product characterization for CAR-T cell therapy drug development efforts

Spotlight Article

Expert Insight

Sadik H Kassim

Latest advances in CAR-T cell manufacturing

Chimeric antigen receptor T (CAR-T) cell therapies have produced remarkable clinical outcomes in relapse/refractory cancer patients. These therapies have also led, in certain cases, to life-threatening side effects. The field is now at a critical juncture where a number of CAR-T cell therapies have completed pivotal trials and are on the path to global registration. However, little is known about how to characterize these ‘living’ drug products before administration and more needs to be understood about how different manufacturing strategies can affect safety and efficacy. Moreover, the interplay between the CAR-T cell therapy drug product and the host-specific microenvironment remains incompletely understood. This brief article will review some of the most common analytical challenges encountered during CAR-T cell therapy drug product development and will propose an integrated analytical characterization strategy that may enable for the rapid and comprehensive development of safer and more effective CAR-T therapies.

Submitted for review: Mar 6 2017 Published: May 4 2017
DOI: 10.18609/cgti.2017.026
Citation: Cell Gene Therapy Insights 2017;3(4), 227-237.
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How short-term gain can lead to long-term pain

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Innovator Insight

David James

Latest Advances in CAR-T Cell Manufacturing

For the commercial success of advanced therapies including CAR-T, they must not only be safe and effective, but also consistently produced and delivered to patients at a cost substantially less than the reimbursable rate. Regardless of whether your therapy is allogeneic or autologous, initial protocols are usually developed using laboratory equipment and skilled research staff completing aseptic operations in BSCs. What many advanced therapy companies either fail to realize or choose to ignore is that the decisions made during early development have a profound and long-lasting impact on the success of the therapy. This article provides valuable insight into some of the factors critical to successful commercialization of an advanced therapy to help prevent short-term gains from becoming long-term pain.

Submitted for review: Jan 16 2017 Published: Apr 10 2017
DOI: 10.18609/cgti.2017.018
Citation: Cell Gene Therapy Insights 2017;3(4), 271-284.
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The regulation of CAR-T cells

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Expert Insight

Shirley M Bartido

Latest advances in CAR-T cell manufacturing

The clinical success of genetically modified T cells utilizing chimeric antigen receptors has been seen in the treatment especially of B cell hematological malignancies in several clinical trials to date. The regulatory requirements for CAR-T cell therapy is a challenging task because of the unique and novel nature of each therapy. The manufacture of genetically modified T cells, whether they are derived from an autologous or allogeneic source, requires reproducibility, safety and efficacy of the final product. Therefore, the regulatory approach taken for these cell therapies is dictated not only by the manufacture of the products but also by their intended clinical use and method of clinical delivery.

Submitted for review: Mar 30 2017 Published: May 4 2017
DOI: 10.18609/cgti.2017.030
Citation: Cell Gene Therapy Insights 2017;3(4), 239-253.
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Progress and challenges in the manufacturing of CAR-T cell therapy

Spotlight Article

Interview

Latest advances in CAR-T cell manufacturing

Dr Bruce Levine

Dr Bruce Levine, Barbara and Edward Netter Professor in Cancer Gene Therapy, is the Director of the Clinical Cell and Vaccine Production Facility (CVPF) in the Department of Pathology and Laboratory Medicine and the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania. He received a BA in Biology from the University of Pennsylvania and a PhD in Immunology and Infectious Diseases from the Johns Hopkins University. The CVPF develops and tests novel cell and gene therapies in clinical trials in patients with hematologic malignancies, solid tumors, HIV infection and genetic disease. First-in-human trials include the first use of a lentiviral vector, the first infusions of zinc finger nuclease genome-modified cells, and the first use of lentivirally-modified cells to treat cancer. Dr Levine has overseen the production, testing and release of 2700 cellular products administered to >1000 patients in clinical trials since 1996. Through these technologies, personalized and enhanced immunity has been engineered. T lymphocytes from HIV+ subjects have been rendered resistant to HIV infection and reinfused. T lymphocytes from cancer patients have been redirected with chimeric antigen receptors to hunt and destroy their malignancies, an investigational therapy that received the first Breakthrough Designation from the FDA for an academic institution and is currently in commercial development. Dr Levine is co-inventor on 23 issued US patents and co-author of >125 publications with a Google Scholar citation h-index of 66. He has been interviewed by the NY Times, Wall Street Journal, Forbes, BBC and other international media outlets.

DOI: 10.18609/cgti.2017.027
Citation: Cell Gene Therapy Insights 2017;3(4), 255-260.
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Challenges & opportunities for manufacturing autologous cellular therapies such as CAR-T cells

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Interview

Latest advances in CAR-T cell manufacturing

Dawn Maier

Dawn has been working in the field of cell and gene therapy for ~ 15 years. She obtained her Masters in Biology in 2002 from Western Carolina University. From 2002 to 2006 she worked in an academic research lab, studying gene therapy and HIV. In 2007, Dawn took a position as a validation scientist at the Clinical Cell and Vaccine Production Facility (CVPF) at University of Pennsylvania. She spent 6 years at UPenn in a number of roles doing not only pre-clinical translational studies but also development of GMP manufacturing processes for numerous autologous cellular and gene therapies in early phase clinical trials. In addition, Dawn was also involved with managing QC/QA operations, preparing for FACT accreditation and contributed to writing IND CMC sections and also a Drug Master File for K562 derived aAPC. Her current position at bluebird bio is as Associate Director of Cellular Process Development and Manufacturing, where she leads the group in the development, optimization and technology transfer of clinical manufacturing processes for cell and gene therapy products. Since joining bluebird, she has participated in the development, translation and tech transfer of the following programs: Lenti-D for adrenoleukodystrophy, Lenti-G for beta-thalassemia and sickle cell disease, and anti-BCMA CAR-T for multiple myeloma.

DOI: 10.18609/cgti.2017.029
Citation: Cell Gene Therapy Insights 2017;3(4), 261-265.
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Goals behind NCI’s T cell manufacturing supplement grant awards

Spotlight Article

Interview

Latest advances in CAR-T cell manufacturing

Dr. Anthony Welch

Dr. Anthony Welch is a Project Officer at National Cancer Institute (NCI)’s Biological Resources Branch where his translational project management experience has enabled moving nine different biologics into clinical trials in the last 12 years. He obtained his BS and MS in Molecular Biology from Drexel University and PhD in Biochemistry and Molecular Biology from The Johns Hopkins University. After completing post-doctoral research at Roche Bioscience in structure-based drug design and enzyme engineering, Dr. Welch worked at biotech companies Bioqual and Wellstat Biologics Corportaion. He also served as adjunct faculty at John Hopkins University and USUHS. Dr. Welch is co-inventor on five US patents and co-author of numerous scientific papers. In his current position at NCI, he is responsible for oversight of translational research projects involving Biologics and Immunotherapeutics (NExT programs) and of a cGMP manufacturing facility for biologics in Frederick, MD. As NCI Program Director, Dr. Welch is also responsible for oversight of a grant portfolio involving Biologic and Immunotherapeutic approaches to treating cancer.

DOI: 10.18609/cgti.2017.028
Citation: Cell Gene Therapy Insights 2017;3(4), 267-270.
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