Addressing the Challenges and Opportunities Presented by Advanced Therapies

Addressing the Challenges and Opportunities Presented by Advanced Therapies

January 15, 2019PAO-M01-19-NI_CL-001

Advanced medicinal products have the potential to transform the pharmaceutical industry. Investment in R&D in the field by companies both large and small is driving advances across the supply chain from drug design to large-scale manufacturing to logistics and patient care.

Advanced Therapy Medicinal Products

Advanced therapies include stem cell therapies, tissue-based and other regenerative medicines, gene and modified cell therapies and immune-oncology drugs. Advanced therapy medicinal products (ATMPs) specifically include drug products derived from living cellular or active genetic materials: somatic cell therapy medicinal products (SCTMPs), tissue engineered medicinal product (TEPs), gene therapy medicinal product (GTMPs) and combined ATMPs. They are being developed to treat and in some cases cure both genetic and non-genetic diseases and injuries, such as skin burns. While the field is in the nascent stage, many candidates are rapidly advancing through the clinic along accelerated approval pathways.

There are currently more clinical trials for cell therapy products than for gene therapies and tissue engineered materials.1 North America is the leader in AMTP development on a geographical basis, in part due to strong support and guidance from the U.S. Food and Drug Administration. European biotechs also receive support from the European Medicine Agency’s Committee for Advanced Therapies. Opportunities are increasing, however, in Asia Pacific countries, such as India, China and Japan.

In 2016, 939 clinical trials investigating ATMPs (85% ongoing, 15% completed) were identified through a search of numerous relevant databases.2 Most were early-phase studies, with just under 7% in phase III. Just over half involved SCTMPs –– approximately 22% each for TEPs and GTMPs –– and 12% were combined products incorporating a medical device. Cancer was the leading targeted disease area (nearly 25%), followed closely by cardiovascular diseases (19.4%). Musculoskeletal (10.5%), immune system and inflammation (11.5%) and neurology (9.1%) were the other notable disease targets. Interestingly, nearly half of the trials involved fewer than 25 patients.

The International Society for Cell and Gene Therapy, in its 2018 annual report on cell and gene therapy market authorizations, identified 44 unique approved products, 84% of which were cell and tissue therapies and 55% of which were autologous.3 More than one-third of the cell, tissue and gene products, (16 in the United States, 14 in Korea, eight in Europe, four in India and Japan, two in Canada, and one each in China and Australia) target oncological or hematologic conditions.

Stem Cell Therapies

Estimates for the compound annual growth rate (CAGR) at which the global market for stem cell therapies is expected to expand range from approximately 9%4 to 15%5. One market research firm predicts that the value for the market will reach $15.63 billion by 2025.3 This estimate includes both autologous and allogeneic adult stem cells (neuronal, hematopoietic, mesenchymal, umbilical cord and others), human embryonic, induced pluripotent and very small embryonic stem cells used in applications ranging from neurology and oncology to the treatment of injuries, cardiovascular diseases, diabetes, incontinence and other conditions, as well as those used in drug discovery and development. Use in regenerative medicine is driving much of the growth of the market.

Adult stem cells dominate the market due to their low rejection rates, long-term renewal properties and lack of concerns over the ethical use of these cell products.4 Interest is growing, however, in the use of stem cells found in umbilical cord blood.5 These cells have been investigated for the treatment of more than 80 diseases, and in 2018 over 200 National Institutes of Health (NIH)–funded clinical trials with cord blood were conducted in the United States alone. 

Gene and Modified Cell Therapies

Gene therapy involves the delivery of genetic material to cells in order to provide a missing gene or replace a nonfunctioning or incorrectly functioning gene with a functioning version. In modified cell therapies, such as chimeric antigen receptor (CAR) T cell therapies, the genetic composition of patient cells is modified using gene-editing technology before they are expanded and returned to the patient.

The delivery vehicle is critical to the success of gene therapies. Currently modified viruses (adeno-associated virus, retrovirus, lentivirus and herpes simplex virus) are widely used as vectors due to their highly evolved ability to deliver nucleic acids. Concerns over viral toxicity, immunogenicity and other issues are driving interest in the development of non-viral vectors for delivery of generic material. While no options are currently in use, rapid advances will make this approach possible in the near future.6

Estimates for the value and growth rate of the global gene therapy market vary significantly. Grand View Research pegs the market value in 2017 at $7.6 million with a CAGR of 19.0% through 2026.6 Transparency Market Research’s numbers are double that: a global market value in 2017 of $17 million with a CAGR of 40.0%.7 The biggest disparity lies with the estimates from Allied Market Research, which puts the value of the global gene therapy market in 2016 at $584 million and expanding to $4.402 billion (33.3% CAGR) by 2023.8 The large discrepancy may be due to the inclusion or exclusion of CAR-T cell therapies as gene therapies. 

All agree that, by indication, the majority of gene therapies are intended as cancer treatments. This result was recently confirmed by a KNect365 Life survey of 165 professionals in industry and academia in North America and Europe.9 Over 60% of respondents said their companies were working on cancer therapies. Other disease areas of focus include rare diseases (29%), autoimmune disorders (24%) and cardiovascular diseases (24%). In addition, half of the survey participants indicated that their companies have CAR-T products in their pipelines –– compared with 18% with TCRs and 17% with dendritic products.

Nearly half of the survey respondents also expect their companies are likely or very likely to submit marketing applications for cell or gene therapy products currently in their pipelines. Meanwhile, nearly two-thirds (61%) believe that allogeneic (off-the-shelf) therapies are better positioned for commercial success than autologous (personalized) therapies due to the ability to access larger patient populations and use standard biotherapeutic production processes combined with lower cost.

With respect to technology advances, survey participants identified several areas where developments are expected, including automation/closed systems (27%), cell and gene engineering –– including CRISPR (clustered regularly interspaced short palindromic repeats) –– (27%) and manufacturing technologies (25%). Less important were analytics (9%), delivery to patient (8%) and supply chain (3%). 

Immuno-Oncology Drugs

Immuno-oncology drugs use the body’s immune system to aid in the treatment of tumors. They are designed to activate a patient’s immune system so that it can better recognize and attack cancer cells. They include monoclonal antibodies, therapeutic vaccines, immune checkpoint inhibitors, CAR-T cell therapies and others.

 RNCOS estimates that the global immuno-oncology market will surpass $100 billion by 2022.10 GlobalData is much more conservative in its prediction, however. This market research firm believes the total immune-oncology market will be worth approximately $34B by 2024.11 The leading product will be Merck’s Keytruda, a PD-1 inhibitor and antibody–drug conjugate with forecast sales of approximately $7 billion.

Many leading biopharmaceutical companies are forming collaborations and licensing agreements with biotech startups focused on developing novel immuno-oncology technologies. The interest in the field is driven by the specificity and increased efficacy of these targeted therapies compared with traditional, systemically administered chemotherapies. In 2017, five new immuno-oncology drugs were approved globally, all with Breakthrough Therapy designations.11

Challenges to Development of ATMPs

Despite the promise of ATMPs and their significant potential to create real market value and provide improved outcomes for patients, few have yet to be approved. In Europe, just 10 ATMPs have been approved since 2009, and not all of them are still on the market. In most cases, withdrawals have occurred for business reasons, not safety issues.12

There are numerous challenges to bringing such advanced therapies to market, from regulatory uncertainties to the need for cost-effective, efficient scalable production processes. Many of the technologies used to produce these drugs are novel and take years (20 for the gene therapy Strimvelis, for example) to develop to a point of commercialization.12 The dollar investment over such long periods is also quite high. Recouping that investment when the drug product is intended to treat a small population can be difficult.

Collaborative Approach to Tackling the Issues

Collaboration between all stakeholders is helping to address some of these issues. The upcoming co-located Phacilitate Leaders World, World Stem Cell Summit (WSCS), Cell & Gene Therapy World, Immuno-Oncology Frontiers World and Cord Blood & Perinatal Stem Cells Summit conferences to be held at the Hyatt Regency Miami, January 22–25, 2019 are specifically designed to bring together senior professionals and stakeholders in cell, gene and immunotherapy in an inclusive and expansive interdisciplinary, networking and partnering meeting in the stem cell science and regenerative medicine field. The meeting is expected to attract 2,000 attendees, 150 exhibitors and 300 speakers representing every major stakeholder group. 

“Phacilitate believes in the power of partnerships and that, through collaboration, anything can be achieved. By fostering the community and bringing together a diverse range of expertise from across the advanced therapies ecosystem, Phacilitate is creating a network of partnerships that brings the industry closer to achieving the ultimate goal of improving patient care and developing commercially viable curative treatments,” says the company’s Director of Advanced Therapies Michael Adeniya. The nonprofit Regenerative Medicine Foundation, which organizes the WSCS, also fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures.

Advances in technology, from scalable manufacturing solutions such as acoustic cell separation to non-viral gene delivery, will be discussed. Approaches to minimizing cost and maximizing the likelihood of regulatory approvals will be tackled. Personal experiences with both success and failure will be conveyed. Convened panels will bring multiple perspectives to different issues, such as standardization and ways in which regulatory rules and guidance can facilitate commercialization of ATMPs. The role of contract manufacturing will be explored. 

Attendees at the January event will learn about all aspects driving the commercialization of advanced therapies on topics including stem cells, immuno-oncology, cord blood, regulatory pathways, reimbursement, research and development, emerging science, translation and clinical trials, cell manufacturing, regenerative medicine in the clinic, ethics and regulation, patient advocacy, funding and much more.

All Pharma's Almanac readers who register for Phacilitate Leaders World & WSCS will receive a 20% discount.




  1. Advanced Therapy Medicinal Products (ATMPs) Market - Global Industry Analysis, Size, Share, Growth, Trends, and Forecast 2017 – 2025. Transparency Market Research. 2018. Web.
  2. Hanna, Eva, Cécile Rémuzat, Pascal Auquier and Mondher Toumi. “Advanced therapy medicinal products: current and future perspectives,” Journal of Market Access & Health Policy. 5:1 (2017).
  3. ISCT publishes annual report on cell and gene therapy market authorizations. International Society for Cell and Gene Therapy 19 2018. Web.
  4. Stem Cell Market Size To Reach $15.63 Billion By 2025 | CAGR: 9.2%. Grand View Research. Jun. 2017. Web.
  5. Stem Cell Application Outlook (Revenue, USD Billion, 2014 – 2025). Mordor Intelligence., May 2018. Web.
  6. Global Gene Therapy Market Size, Analysis | Industry Report 2018-2026. Grand View Research. May 2018. Web.
  7. Gene Therapy Market: New Product Approvals and Commercialization to Boost Market. Transparency Market Research. 8 Nov. 2018. Web.
  8. Gene Therapy Market Expected to Reach $4,402 Million, Globally, by 2023. Allied Market Research. 2017. Web.
  9. Burrows, Andrew. “The current state and future of cell and gene therapies - Data report analysis.” Knect365. 17 2018. Web.
  10. Immuno-Oncology Market, By Type [mAb (Naked, Conjugate), Cancer Vaccines, Immune Checkpoint Inhibitors (PD-1, PD-L1, CTLA-4]), By Application (Lung, Melanoma, Leukemia, Lymphoma) - Global Forecast to 2022. Aug. 2018. Web.
  11.  GlobalData Healthcare. “Will immuno-oncology bring a new era of blockbuster drugs?Pharmaceutical Technology. 5 Sep. 2018. Web.
  12. Cynober, Timothé. “Why Are There Only 10 Cell and Gene Therapies in Europe?” Labiotech. 4 Apr. 4, 2018. Web.
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