Chris Mason, Elisa Manzotti, & Emily J Culme-Seymour
Citation: Cell Gene Therapy Insights 2016;2(2), 141-145.
Citation: Cell Gene Therapy Insights 2016;2(2), 141-145.
Although cystic fibrosis (CF) occurs due to a recessive mutation in a single gene, gene therapy to correct this defect has remained unrewarding. In fact, until recently the scientific and medical community has only been able to treat the varying symptoms of the disease; but recent advances offer much hope for the treatment of the underlying genetic defect. CF predominates in Caucasians compared to other races and Ireland has the highest carrier rate in the world (1 in 19) and a CF prevalence of 2.98 per 10,000 live births. This is four times higher than that of the USA or the European Union (EU) average, where the cost of CF healthcare approximates to €0.6 billion per annum [1,2]. While advances in recent years have improved treatment and lengthened the median survival of people with CF, there is still no effective cure.
Citation: Cell Gene Therapy Insights 2016;2(2), 147-152
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.
Investors looking for an opportunity to gain exposure to gene editing technologies on the public markets were given their second opportunity this past month after Intellia Therapeutics closed its initial public offering raising net proceeds of just under $113 million. One of its close competitors, Editas Medicine, went public only months ago raising $94 million to list on the NASDAQ. Gene editing technologies can be applied as in vivo gene therapies, or be leveraged ex vivo to produce cell-based gene therapies. While these cutting edge technologies offer fundamentally game changing advances to the field, investing in their equities comes with the challenge of volatility following go-public transactions. Like many of the cell-based immunotherapy companies that went public in 2015, Editas’ massive gains post-IPO were followed by a crash in stock price. For investors that have the risk tolerance appropriate for early-stage platform technologies poised to enter the clinic, Editas and Intellia are buy and hold for the long-term. What is yet to be determined is who will win the ongoing patent battle over CRISPR/Cas9 claims, which will be a future twist that adds further volatility to the system.
The announcement between Biogen and U. Penn is yet another example of Big Pharma discovering the value of taking cell and gene therapy products seriously. They were there at the dawn of gene therapy development and then got ‘cold feet’ and avoided the area, particularly after the death of Jesse Gelsinger. However now that most of the hard work has been done by small companies and academic groups and as some of these products have come closer to market, ‘Big Pharma’ has come back in – well…better late than never!
Dr Alexey Bersenev, Yale University, USA, provides an expert overview of the most important clinical trials, cases and cohort studies conducted in academic and industry with particular focus on later-stage efficacy data.
Citation: Cell Gene Therapy Insights 2016; 2(2), 169-174.
Submitted: Apr 15 2016 Published: Jul 5 2016
Citation: Cell Gene Therapy Insights 2016;2(2), 175-182
This article describes the regulatory pathway that enabled the translation of academic research and clinical experience of an ex-vivo expanded autologous stem cell-based treatment for limbal stem cell deficiency (LSCD) into a pharmaceutical product compliant with the European Union regulations of Advanced Therapy Medicinal Products (ATMP). Holoclar® was originally developed in Italy as a surgical procedure and used in more than 200 patients. Following the establishment of the EU ATMP Regulation EC 1394/2007, Holoclar development required that manufacturing was as per current Good Manufacturing Practice requirements and collection of retrospective clinical data was ICH-E6 and E3 compliant. Holoclar is an ex-vivo expanded autologous human corneal epithelial cells containing stem cells and is classified as “tissue engineered product”. Based on the evidence of quality and control of the manufacturing process, safety, efficacy and on a positive benefit–risk balance in 104 patients (72.1%) of 148 patients treated, Holoclar received conditional Marketing Approval in the EU. Holoclar is the first medicine approved in the EU for this rare eye condition that can result in blindness.
Submitted for Review: Mar 30 2016 Published: Jul 5 2016
Citation: Cell Gene Therapy Insights 2016;2016;2(2), 183-197.
In Part One of our Cell & Gene Therapy Manufacturing Pathway spotlight series we focused on the early stages of product development, examining the key attributes that will eventually impact commercial viability. Part Two takes us on a step to evaluate potential solutions to the core manufacturing and logistical challenges involved in cost-effectively delivering cell and gene therapies to patients.
Citation: Cell Gene Therapy Insights 2016; 2(2), 221-222.
While cell and gene therapy products share the same goal for their cold chains as standard pharmaceutical and biological products, namely to ensure the product is maintained within appropriate temperature specifications en route to the patient, there are specific features of cell therapy products that make their cold chains uniquely challenging. This article reviews the requirements of cold chains for these products, highlights some of the current challenges and discusses some of the technologies being developed to facilitate the creation of commercial cold chains for these advanced medicinal products.
Dr Phil Vanek is General Manager of GE Healthcare’s Cell Therapy Technologies business, a business initiative funded in part by GE Healthymagination, a $6 billion strategy to revolutionize the world’s health by improving the quality, access and affordability of care. Prior to joining GE, Phil was Head of Innovation for Lonza’s Pharmaceutical division, leading a group of research scientists, process development engineers, and commercial strategists to drive new technology initiatives focused on cell, protein, and viral therapeutic manufacturing. Phil’s career has included a number of senior innovation, business and market development roles at Becton Dickinson, Invitrogen, and Life Technologies, as well as two start-up biotechnology companies in the Washington, DC area. Phil received his Ph.D. in Biochemistry and Molecular Biology from Georgetown University Medical Center and subsequently held an IRTA fellowship at the National Cancer Institute in the Laboratory of Molecular Oncology. Phil is an active member of the Alliance for Regenerative Medicine, where he currently serves as an Officer of the Executive Committee. Phil has also been recently elected to the Centre of Commercialization of Regenerative Medicine (CCRM) Board of Directors in Toronto, Canada, and serves on the Editorial Board of Cell and Gene Therapy Insights
Cell therapies are a promising class of biologics which exhibit many capabilities not available to other pharmaceuticals. Cells can respond to their environment in a conditional and multifunctional manner, and in some cases can home to specific regions or proliferate within the patient. These unique properties enable new therapeutic approaches to treat patients’ unmet medical needs. However, there are also new challenges that extend all the way to the patient’s bedside. With a medicinal product that is alive, the delivery and administration procedures must be designed and controlled to ensure cellular health, while also managing the complexity and biological limitations of specific cell types. As a practical matter, solutions must align with existing medical infrastructure to get viable drug products to the patient populations who need it. From an industry perspective, the goals around clinical preparation and administration are to provide a safe and effective therapy in a standardized manner that is operationally efficient and robust.
Dr Rivière received her PhD in Cellular and Molecular Biology from the University of Paris. She initiated her graduate studies at the Institut Curie in Paris and completed her thesis in the laboratory of Dr.Mulligan at the Whitehead Institute in Cambridge, MA. During this time, she developed novel retroviral vectors for in vivo long-term expression of transgenes in hematopoietic cells using MFG/SFG-based retroviral vectors that are widely used in clinical studies for the treatment of genetic and acquired disorders. She is currently the Director of the Michael G. Harris Cell Therapy and Cell Engineering Facility where she investigates the genetic modification of hematopoietic cells to increase or retarget the immune response against tumors. Her laboratory has developed cell manufacturing platforms under cGMP conditions for several Phase I/II clinical trials and currently supports 8 CAR-T cell based clinical trials under 5 INDs at MSK. She actively participated in the National Cell Manufacturing Consortium Workshop that has led to the establishment of the Technology Roadmap to 2025 for Achieving Large Scale, Cost effective, Reproducible Manufacturing of High-Quality Cells.
Dr. Kunkel has over 12 years of experience in biotechnology including executive positions in R&D, entrepreneurship and start-ups, and consulting for technology and diagnostics companies. As an entrepreneur, he co-founded Ascellna Life Science Group, a business development and commercialization company for small companies with innovative technologies. As VP, Assay Development and Screening at Catalyst Biosciences, Inc., Dr. Kunkel led the optimization of the company’s Alterase technology platform, which successfully generated multiple development candidates. Dr. Kunkel has published 37 articles in peer-reviewed journals and has contributed to multiple patents and patent applications. He holds a BSc in Chemical Engineering from the University of Notre Dame, MS and PhD degrees in Biomedical Engineering from the University of Virginia, and was a postdoctoral fellow at Stanford University.
Industry 4.0 foresees a digital transformation of manufacturing resulting in smart factories and supply chains. At the heart of the concept lies the vision of interconnected materials, goods and machines, where goods find their way through the factory and the supply chain to the customer in a self-organized manner. Industry 4.0 is gaining traction in high value manufacturing sectors. This expert insight article explores what this technology-driven vision has to offer the biopharmaceutical industry, and in particular cell and gene therapies.
Kevin O’Donnell is widely considered one of the principal architects of the modern-day pharmaceutical cold-chain movement. He is internationally respected and uniquely qualified as a tireless advocate, author, blogger, educator, training developer, and champion of good distribution and logistics practices for temperature-sensitive drugs. His pioneering efforts for the advancement of good practices are reflected in his various roles within the industry: as a member of the United States Pharmacopeia (USP) Expert Committee on Packaging, Storage and Distribution; temporary advisor and certified mentor to the World Health Organization (WHO); co-author of PDA Technical Report No. 39; a member of the International Safe Transit Association (ISTA) Thermal Council; and the former chair of the International Air Transport Association (IATA) Time & Temperature Task Force. Prior positions include: Senior Partner at Exelsius Cold Chain Management Consultancy US, an international provider of consultative, research, and training services to manufacturers, airlines, forwarders, and other stakeholders in the life science logistics sector; Director & Chief Technical Advisor at ThermoSafe Brands; and Principle Packaging Engineer at Abbott Laboratories Global Pharmaceutical Division, from where he retired in 2005 after a 26-year career.
Personalized medicine is an innovative approach to disease prevention and treatment that takes into account differences in how individuals respond to medication. Advances in personalized medicine have already led to powerful new discoveries and approved treatments that are tailored to specific characteristics of individuals, such as a person’s genetic makeup, or the genetic profile of an individual’s tumor. Autologous cell therapies are arguably one of the most personalized forms of medicine, using a patient’s own cells to generate a bespoke product that is only administered back to the original donor. This article discusses the emerging role of personalized medicine in various cell and gene therapies, its role in health economics and challenges to its implementation.
Submitted for review: April 21 2016 Published: June 21 2016
Citation: Cell Gene Therapy Insights 2016; 2(2), 277-286.
Objective: Bone marrow cell therapy has pioneered the field of regenerative medicine for the treatment of ischemic disease, but remains a controversial topic due to persistent uncertainty on purity and quality of the cell product. Here, we evaluated the therapeutic activity of pro-angiogenic clones derived from single-sorted long-term repopulating hematopoietic stem cells (LT-HSCs, CD150+/CD34–/Lineage-/Sca-1+/c-Kit+) in a murine model of hindlimb ischemia. Approach and Results: C57BL/6 mice underwent unilateral limb ischemia by femoral artery occlusion, followed by intramuscular injection of green fluorescent BM LT-HSCs cells (2,000 per mouse) from congenic donor C57BL/6-Tg(CAG-EGFP)131Osb/LeySopJ mice or vehicle (PBS). Cell therapy with LT-HSCs markedly accelerated the recovery of blood flow to the ischemic limb as measured by laser Doppler flowmetry (P2, P<0.05) and arteriole density (108 ±6 vs. 72 ±9/mm2, P<0.05). Additionally, LT-HSC therapy improved the viability and proliferation of resident vascular cells. In separate experiments, single sorted BM LT-HSC-derived cells were expanded up to 40,000 fold in culture giving rise to two distinct clone subsets, according to the expression level of the surface marker CD31. Upon transplantation in the mouse ischemic model, CD31high LT-HSC-derived cells showed superior pro-angiogenic and pro-healing activities as compared with CD31low LT-HSC-derived cells. Conclusions: These data establish clonogenic CD31high LT-HSC-derived cells as a promising cell therapy approach for the treatment of limb ischemia.
*Authors contributed equally to this paper
Submitted for review: Dec 2 2015 – Revised Accepted: Apr 20 2016 – Published: Jul 5 2016
Citation: Cell Gene Therapy Insights 2016; 2(2), 199-217.