Biopharma is focused on streamlining biomanufacturing and supply chain issues to drive adoption 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 diseases untouched by small molecule and biological agents. Over the past two decades, more than 20 CGTs have been approved by the FDA in the United States, and many of these one-time treatments cost between $375.00 and $2 million per injection (1). Given the high financial cost and patient expectations of these life-saving therapies, it is imperative that manufacturers offer integrated services across the supply chain to ensure efficient biological manufacturing processes and seamless logistics to break down barriers to uptake.
The following details the who, what, when and why of biomanufacturing and logistics in CGTs in the bio/pharmaceutical industry.
Who: winners and losers
According to market research, the global gene therapy market will reach US$9.0 billion by 2027, reflecting favorable reimbursement policies and policies, product approvals and fast-track designations, a growing demand for T-cell-based chimeric antigen receptor-based gene therapy (CAR) and improvements in RNA, DNA, and oncolytic viral vectors (1).
In 2020, CGT manufacturers received around 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 CDMO CELLforCURE, Roche/Spark Therapeutics and Smith & Neffe /Osiris Therapeutics.
Many bio/pharmaceutical companies are rethinking their commercialization strategies and have reinvested in R&D to standardize vector production and purification, implement advanced techniques in cell therapies and improve cryopreservation of cell samples, and explore off-the-shelf development -allogeneic cell solutions on the shelf (2).
The successful development of CGTs has revealed major bottlenecks in production facilities and at times a shortage of raw materials (3). Pharmaceutical companies are now taking a close look at their in-house capabilities and are 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 capabilities (4). Recently, several CDMOs—Samsung Biologics, Fujifilm Diosynth, Boehringer Ingelheim, and Lonza—have all expanded their biomanufacturing facilities to meet demand (5).
A major challenge for CGT manufacturers is the seamless delivery of advanced therapies. There’s no room for error. If manufacturers cannot easily deliver the CGT therapy to the patient, the effectiveness 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 functional. Therefore, manufacturers must not only comply with regulations, but also set up logistical processes and contingency plans to optimize tracking, packaging, cold storage and transport throughout the product journey. Time is of the essence, and several manufacturers have failed to meet patient demands, having a significant impact on the applicability of these agents.
What: Leading innovators
Several CAR T cell therapies have now been approved; However, research shows that one-fifth of cancer patients who are candidates for CAR-T therapies die while waiting for a place in production (6). While many of these endogenous products initially took around a month to manufacture, certain active ingredients can now be manufactured in less than two weeks (7). Companies are exploring new ways to reduce vein-to-vein (collection and reinfusion) time by developing more advanced gene delivery tools using CARs (such as transposon, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) among others) and using a centralized organization with standardized apheresis centers (5) Others are investigating the use of allogeneic stem cells, including Regen Biopharma, Escape Therapeutics, Lonza, Pluristem Therapeutics and ViaCord (7).
Several gene therapies have also been approved, mainly to treat rare diseases (8). Many companies are evaluating novel gene therapy vectors to increase gene expression/protein production, reduce immunogenicity and improve shelf life 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 biopharmaceutical companies have built their own internal CGT good manufacturing practice (GMP) operational capabilities, others are attempting 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).
When: New arrivals
The top 50 gene therapy start-up companies have attracted more than $11.6 billion in funding over the past few years, with the top 10 companies raising $5.3 billion in Series A through D funding rounds ( 10). US-based Sana Biotechnology is a leader in the field, raising $700 million for the development of scalable genetically engineered cell manufacturing and its pipeline program that will advance CAR-T cell-based therapies in oncology and human cancer CNS (central nervous system) disorders (11). In second place, Editas Medicine received $656.6 million to develop CRISPR nuclease gene editing technologies to develop gene therapies for rare diseases (12).
Why: Plus sign and minus sign
Overall, CGTs have attracted the attention of the pharmaceutical industry as they offer an alternative avenue to combat diseases that are poorly managed by pharmaceutical and/or medical interventions, such as: B. Rare and rare diseases. Private investors continue to invest money in this sector because a single injection has the potential to bring long-lasting clinical benefits to patients (13). In addition, regulators have approved several products and introduced fast-track approval to expedite patient access to these life-saving medicines. Additionally, healthcare providers have implemented reimbursement policies and manufacturers have negotiated value- and outcome-based contracts to break down barriers to access these high-priced products
On the other hand, manufacturing CGTs is labor intensive and expensive as manufacturing accounts for about 25% of operating costs, and 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 may not show a sustained response due to prior exposure to the viral vector, poor gene expression, and/or development of immunogenicity due to prior exposure to viral vectors. Those who can receive these therapies can suffer from 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 significant advances made to date in the field of CGT, much work remains to improve the durability of reactions, increase the efficiency and consistency of biological manufacturing, and implement a seamless supply chain that can ensure that these active ingredients are accessible and inexpensive. effective and a sustainable option for those in need.
references
- market reports, Insights into the gene therapy market (September 2022).
- E.Capra, et al., McKinsey Insights on Cell and Gene TherapyMcKinsey & Company (2022).
- J. Chapman, “FDA Addresses Challenges in Cell and Gene Therapy Manufacturing,” Redica Systems, November 5, 2020.
- N. Pike, “Build vs. Buy Dilemma – Economics of Manufacturing Cell-Based Therapies”, Insights into cell and gene therapyBioinsights Publishing Limited, July 28, 2022.
- P. Van Arnum, “CDMOs Invest in Biomanufacturing, Cell & Gene Therapy Manufacturing”, Insights into the DCAT value chainSeptember 14, 2021.
- BioSpace, “Allogeneic Stem Cell Therapy Market: Therapeutics Company Segment Offers Attractive Opportunities”, BioSpace.comFebruary 7, 2021.
- Binocs, “Industrialization of the next generation of cell and gene therapies”,
White paper, Discover-binocs.comaccessed September 19, 2022. - P. Van Arnum, “Cell and Gene Therapies: A Manufacturing View”, Insights into the DCAT value chainApril 24, 2019.
- C. Hildreth, “Cell Therapy CDMO – Role of Contract Manufacturing for Cell Therapy”, Bioinformant.comNovember 26, 2017.
- Medical Startups, “Top Gene Therapy Companies”, MedicalStartups.org,
September 13, 2022. - Sana Biotechnology, our science, sana.comaccessed September 19, 2022
- Editas Medicine, our research and
Pipeline, Editasmedicine.comaccessed September 19, 2022. - D. Crean, “The Market for Cell and Gene Therapy: Comes to fruition,” PharmaBoardroom.comJune 27, 2022.
- Cleveland Clinic, “CAR T-Cell Therapy: Procedure, Prognosis & Side
Effects,” my.clevelandclinic.orgaccessed September 19, 2022.
About the author
Cleo Bern Hartley is a pharmaceutical consultant, former pharmaceutical analyst and research scientist.
item details
pharmaceutical technology
Volume 46, number 10
October 2022
Pages: 54-55
Citation
When referring to this article, please cite it as CB Hartley, “Growth in Cell and Gene Therapy Market”, pharmaceutical technology 46(10) 54-55 (2022).
