Biopharma focuses on streamlining biomanufacturing and supply chain issues to drive uptake of cell and gene therapies.
Cell and gene therapies (CGTs) offer significant advances in patient care by helping to treat or potentially cure a range of conditions that have been untouched by small molecule and biologic agents. Over the past two decades, more than 20 CGTs have been approved by FDA in the United States and many of these one-time treatments cost between US$375,00 and US$2 million a shot (1). Given the high financial outlay and patient expectations of these life-saving therapies, it is essential that manufacturers provide integrated services across the whole of the supply chain to ensure efficient biomanufacturing processes and seamless logistics to reduce barriers to uptake.
The following looks at the who, what, when, and why of biomanufacturing and logistics in CGTs in the bio/pharmaceutical industry in more detail.
According to market research, the global gene therapy market will reach US$9.0 billion by 2027 due to favorable reimbursement policies and guidelines, product approvals and fast-track designations, growing demand for chimeric antigen receptor (CAR) T cell-based gene therapies, and improvements in RNA, DNA, and oncolytic viral vectors (1).
In 2020, CGT manufacturers attracted approximately US$2.3 billion in investment funding (1). Key players in the CGT market include Amgen, Bristol-Myers Squibb Company, Dendreon, Gilead Sciences, Novartis, Organogenesis, Roche (Spark Therapeutics), Smith Nephew, and Vericel. In recent years, growth in the CGT market has fueled some high-profile mergers and acquisitions including bluebird bio/BioMarin, Celgene/Juno Therapeutics, Gilead Sciences/Kite, Novartis/AveXis and the CDMO CELLforCURE, Roche/Spark Therapeutics, and Smith & Nephew/Osiris Therapeutics.
Many bio/pharma companies are re-considering their commercialization strategies and have re-invested in R&D to standardize vector productions and purification, implement forward engineering techniques in cell therapies, and improve cryopreservation of cellular samples as well as exploring the development of off-the-shelf allogeneic cell solutions (2).
The successful development of CGTs has highlighted major bottlenecks in the manufacturing facilities, and at times, a shortage of raw materials (3). Pharma companies are now taking a close look at their internal capabilities and either investing in their own manufacturing facilities or outsourcing to contract development and manufacturing organizations (CDMOs) or contract manufacturing organizations (CMOs) to expand their manufacturing abilities (4). Recently, several CDMOsSamsung Biologics, Fujifilm Diosynth, Boehringer Ingelheim, and Lonzahave all expanded their biomanufacturing facilities to meet demand (5).
A major challenge for CGT manufacturers is the seamless delivery of advanced therapies. There is no room for error. If manufacturers cannot deliver the CGT therapy to the patient with ease, the efficacy of the product becomes obsolete. Many of these therapies are not off-the-shelf solutions and therefore require timely delivery and must be maintained at precise temperatures to remain viable. Thus, manufacturers must not only conform to regulations, but they must also put in place logistical processes and contingency plans to optimize tracking, packaging, cold storage, and transportation through the products journey. Time is of the essence, and several manufacturers have failed to meet patient demands, which have significant impacts on the applicability of these agents.
Several CAR T-cell therapies have now been approved; however, research indicates that a fifth of cancer patients who are eligible for CAR-T therapies pass away while waiting for a manufacturing slot (6). Initially, the manufacture of many of these autologous products took around a month, but certain agents can now be produced in fewer than two weeks (7). Companies are exploring new ways to reduce vein-to-vein time (collection and reinfusion) through the development of more advanced gene-transfer tools with CARs (such as transposon, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) among others, and the use of centralized organization with standardized apheresis centers (5). Others are exploring the use of the of allogeneic stem cells including Regen Biopharma, Escape Therapeutics, Lonza, Pluristem Therapeutics, and ViaCord (7).
Several gene therapies have also been approved, mainly in the treatment of rare disease (8). Many companies are evaluating novel gene therapy vectors to increase levels of gene expression/protein productions, reduce immunogenicity and improve durability including Astellas Gene Therapies, Bayer, ArrowHead Pharmaceuticals, Bayer, Bluebird Bio, Intellia Therapeutics, Kystal Biotech, MeiraGTx, Regenxbio, Roche, Rocket Pharmaceuticals, Sangamo Therapeutics, Vertex Pharmaceuticals, Verve Therapeutics, and Voyager Therapeutics (8).
While many biopharma companies have established their own in-house CGT good manufacturing practice (GMP) operation capabilities, others are looking to decentralize manufacturing and improve distribution by relying on external contracts with CDMOs and CMOs such as CELLforCURE, CCRM, Cell Therapies Pty Ltd (CTPL), Cellular Therapeutics Ltd (CTL), Eufets GmbH, Gravitas Biomanufacturing, Hitachi Chemical Advances Therapeutic Solutions, Lonza, MasTHerCell, MEDINET Co., Takara Bio, and XuXi PharmaTech (6, 9, 10).
The top 50 gene therapy start-up companies have attracted more than $11.6 billion in funds in recent years, with the top 10 companies generating US$5.3 billion in series A to D funding rounds (10). US-based Sana Biotechnology leads the field garnering US$700 million to develop scalable manufacturing for genetically engineered cells and its pipeline program, which include CAR-T cell-based therapies in oncology and CNS (Central Nervous System) disorders (11). In second place, Editas Medicine attracted $656.6 million to develop CRISPR nuclease gene editing technologies to develop gene therapies for rare disorders (12).
Overall, CGTs have attracted the pharma industrys attention as they provide an alternative route to target diseases that are poorly served by pharmaceutical and/or medical interventions, such as rare and orphan diseases. Private investors continue to pour money into this sector because a single shot has the potential to bring long-lasting clinical benefits to patients (13). In addition, regulators have approved several products and put in place fast track designation to speed up patient access to these life-saving medicines. Furthermore, healthcare providers have established reimbursement policies and manufacturers have negotiated value- and outcome-based contracts to reduce barriers to access to these premium priced products
On the downside, the manufacture of CGTs is labor intensive and expensive with manufacturing accounting for approximately 25% of operating expenses, plus there is still significant variation in the amount of product produced. On the medical side, many patients may not be suitable candidates for CGTs or not produce durable response due to pre-exposure to the viral vector, poor gene expression, and/or the development of immunogenicity due to pre-exposure to viral vectors. Those that can receive these therapies may suffer infusion site reactions, and unique adverse events such as cytokine release syndrome and neurological problems both of which can be fatal if not treated promptly (14).
Despite the considerable advances that have been made in the CGT field to date, there is still much work needed to enhance the durability of responses, increase biomanufacturing efficiencies and consistency and to implement a seamless supply chain that can ensure these agents are accessible, cost-effective, and a sustainable option to those in need.
Cleo Bern Hartley is a pharma consultant, former pharma analyst, and research scientist.
Pharmaceutical TechnologyVolume 46, Number 10October 2022Pages: 54-55
When referring to this article, please cite it as C.B. Hartley, "Growth in Cell and Gene Therapy Market," Pharmaceutical Technology 46 (10) 5455 (2022).
See the rest here:
Growth in Cell and Gene Therapy Market - Pharmaceutical Technology Magazine
- New Atlas of Rare Stem and Progenitor Cells Reveals New Cell Types - Inside Precision Medicine - March 28th, 2024
- Instructing iPS cell-derived mesenchymal stem cells to inhibit abnormal bone formation in FOP - Medical Xpress - March 28th, 2024
- GLP podcast: GE crops have lived up to the hype; Growing 'mini' organs from stem cells; How do we solve right-wing ... - Genetic Literacy Project - March 28th, 2024
- Exosomes and Stem Cells Are the Future of Anti-Aging - NewBeauty Magazine - March 28th, 2024
- Stem cells: past, present, and future - PMC - National Center for ... - March 19th, 2024
- Stem cells: a comprehensive review of origins and emerging clinical ... - March 19th, 2024
- Biology of stem cells: an overview - PMC - National Center for ... - March 19th, 2024
- What are Stem Cells? - Types, Applications and Sources - BYJU'S - March 19th, 2024
- Stem Cell - The Definitive Guide | Biology Dictionary - March 19th, 2024
- Colossal Creates Elephant Stem Cells for the First Time in Quest to Revive the Woolly Mammoth - Singularity Hub - March 19th, 2024
- Florida congresswoman sued the Pentagon over stem cells. One problem: her husband's stocks - Raw Story - January 23rd, 2024
- Can Stem Cells Improve Knee Pain or Are They A Waste of Money? - Bloomberg - January 23rd, 2024
- Stem cells used to successfully treat arthritis in gorilla at Budapest zoo - University of Sheffield News - January 23rd, 2024
- A computational model of stem cells' internal mechanism to recapitulate spatial patterning and maintain the self ... - Nature.com - January 23rd, 2024
- Advancing the generation of in-vivo chimeric lungs in mice using rat-derived stem cells - EurekAlert - January 6th, 2024
- 'I couldn't just give up on my dad' | Round Rock son donates stem cells to father battling leukemia - KVUE.com - January 6th, 2024
- Closing in on the ultimate quest to regenerate insulin in pancreatic stem cells - Medical Xpress - January 6th, 2024
- Ask the doctors: Research being conducted on using stem cells to treat diabetes - The Spokesman Review - January 6th, 2024
- Regenerative Medicine and COPD: Generating Functional Lungs from Pluripotent Stem Cells - Medriva - January 6th, 2024
- What is a stem cell? YourGenome - December 2nd, 2023
- Stem cell transplant - NHS - December 27th, 2022
- Stem cells: a brief history and outlook - Science in the News - December 27th, 2022
- RUDN Physician And Russian Scientists Investigate Long-term Effects Of Treating Diabetic Ulcers With Stem Cells - India Education Diary - December 27th, 2022
- Stem Cell Basics | STEM Cell Information - National Institutes of Health - December 2nd, 2022
- Neural stem cell - Wikipedia - November 24th, 2022
- Donate Stem Cells | Bone Marrow Donation - American Cancer Society - November 24th, 2022
- Stem Cells- Definition, Properties, Types, Uses, Challenges - November 6th, 2022
- Brothers from Karnataka, Prapul and Prajwal donated their stem cells, save two blood cancer patients - APN News - November 6th, 2022
- Getting These Stem Cells Treatments: Crippled Ronnie Coleman Gives a Positive Update on His Ability to Walk - EssentiallySports - October 21st, 2022
- Cornell Prof Explains Relevance of Creating Mouse Embryos from Stem Cells - Cornell University The Cornell Daily Sun - October 13th, 2022
- Human neuron clusters transplanted into rats offer new tool to study the brain : Shots - Health News - NPR - October 13th, 2022
- The neuroprotective effects of dental pulp stem cells and erythropoietin in mice hippocampus after ischemia-reperfusion - Newswise - October 13th, 2022
- A $7 million grant to grow stem cell research - Swinburne University of Technology - October 13th, 2022
- Stem Cell Manufacturing Global Market Report 2022: Widespread Product Utilization in Effective Disease Management, Personalized Medicine, and Genome... - October 13th, 2022
- Brennand named Elizabeth Mears and House Jameson Professor of Psychiatry - Yale News - October 13th, 2022
- American Academy of Stem Cell Physicians to Offer Licensed Physicians Board Examination in Regenerative Medicine - BioSpace - October 13th, 2022
- Stem Cells - alsa.org - October 4th, 2022
- Mouse embryo models built from stem cells take shape in a dish - Nature.com - October 4th, 2022
- Therapeutic Solutions International Identifies CD103 Expressing Dendritic Cells and Exosomes Thereof as Novel Mechanism for JadiCell Mesenchymal Stem... - October 4th, 2022
- Aileron Therapeutics Announces Oral Presentation of Non-Clinical Data Demonstrating ALRN-6924 Protected Human Hair Follicles and Their Stem Cells from... - October 4th, 2022
- Research Shows Promise for Directing Later Lines of Therapy for Hodgkin Lymphoma - Targeted Oncology - October 4th, 2022
- Hereditary E200K mutation within the prion protein gene alters human iPSC derived cardiomyocyte function | Scientific Reports - Nature.com - September 25th, 2022
- How To Eat Your Way to Better Health According to a Doctor - Eat This, Not That - September 25th, 2022
- Phio Pharmaceuticals Announces Preclinical Data Demonstrating PH-762 Enhances Persistence of T cells for Tumor Cell Killing as Presented by Helmholtz... - September 25th, 2022
- Types of blood cancer: Leukemia, lymphoma, and more - Medical News Today - September 25th, 2022
- September: er-blood | News and features - University of Bristol - September 25th, 2022
- Here Is Why You Heal Slower As You Age - Health Digest - September 25th, 2022
- Global Single Cell Analysis Market is Projected to Grow at a CAGR of 15.1% By 2032: Visiongain Reports Ltd - Yahoo Finance UK - September 25th, 2022
- Findings explain exceptional auditory abilities in Williams-Beuren Syndrome - EurekAlert - September 25th, 2022
- Finding the potency in planarians | Communications Biology - Nature.com - September 16th, 2022
- Life-Saving Innovations in Cancer-Fighting Stem Cell Transplants and Pioneering Research in HIV, Autism and Cerebral Palsy to be Featured at World... - September 16th, 2022
- Treating Cancer with Oncolytic Viruses - BioPharm International - September 16th, 2022
- Israel's Profuse Technology Raises $2.5M for Technology That Lowers Cost of Cultured Meat - The Spoon - September 16th, 2022
- Stem Cells Used to Grow Mouse Embryo - BioTechniques - September 8th, 2022
- Largest Gift in UCSD History to Fund Stem Cell Research on Space Station - Times of San Diego - September 8th, 2022
- Global Induced Pluripotent Stem Cells Market (2022 to 2027) - Growth, Trends, Covid-19 Impact and Forecasts - ResearchAndMarkets.com - Business Wire - September 8th, 2022
- Health on the Frontlines: The Healing Power of Stem Cells - Dans Papers - September 8th, 2022
- Top 3 grants in regenerative medicine: July 2022 - RegMedNet - September 8th, 2022
- Childhood leukemia treatment 2022: Where we are now and what it takes - EurekAlert - September 8th, 2022
- Treatment Choices for AML Were Increasingly Influenced by Immunological Responses - Physician's Weekly - September 8th, 2022
- BioRestorative Therapies to Present at the H.C. Wainwright 24th Annual Global Investment Conference on September 14 - StreetInsider.com - September 8th, 2022
- Global Recombinant Cell Culture Supplements Market Report 2022: Increasing Need for Immunotherapies and Stem Cell and Regenerative Medicines Presents... - September 8th, 2022
- CAR-T Beyond CGTs In Development In 2022 - BioProcess Online - September 8th, 2022
- ADOCIA Announces First Cell Therapy Preclinical Proof of Concept of AdoShell Islets for the Treatment of Type 1 Diabetes - Business Wire - September 8th, 2022
- Synthetic Mouse Embryo with Brain and Beating Heart Grown from Stem Cells - Genetic Engineering & Biotechnology News - August 30th, 2022
- Utilization of Modified Induced Pluripotent Stem Cells as the Advance | OPTH - Dove Medical Press - August 30th, 2022
- Rise In Number Of CROS In Various Regions Such As Europe Is Expected To Fuel The Growth Of Induced Pluripotent Stem Cell Market At An Impressive CAGR... - August 30th, 2022
- Brush Up: Hematopoietic Stem Cells and Their Role in Development and Disease Therapy - The Scientist - August 30th, 2022
- Regenerative Properties of the Newborn Heart Offers Hope for Those With Congenital Heart Disease - The Epoch Times - August 30th, 2022
- Kanpur hospital is Indias first to perform fat-derived stem cell transplant for diabetic patients - India Today - August 30th, 2022
- Scientists Just Genetically Edited a Million Years of Evolution Into Mouse DNA - ScienceAlert - August 30th, 2022
- Canadian Blood Services Stem Cells for Life - August 22nd, 2022
- Scientists say they have created 'embryos' without sperm or eggs - Medical News Today - August 22nd, 2022
- Many stem cell lines used for research and therapies carry large number of mutations, Cambridge researchers find - Cambridge Independent - August 22nd, 2022
- Scientists hope to revive extinct mammal through stem cells and gene-editing in a first - The Mirror - August 22nd, 2022
- Stem cell therapy in capsule form - Malaya - August 22nd, 2022
- Cell Culture Technician Pluripotent Stem Cell Biology and Genome Editing job with UNIVERSITY OF SOUTHAMPTON | 305107 - Times Higher Education - August 22nd, 2022
- Long COVID-19 and other chronic respiratory conditions after viral infections may stem from an overactive immune response in the lungs - The... - August 5th, 2022
- Self-organized anteroposterior regionalization of early midbrain and hindbrain using micropatterned human embryonic stem cells - Newswise - July 27th, 2022
- Synthetic Stem Cells Market 2022 Size, Share, Future Plans, Competitive Landscape and Forecast to 2030 This Is Ardee - This Is Ardee - July 27th, 2022