In 2017, the world witnessed a historic CAR-T cell therapy approval when on August 30, 2017, Tisagenlecleucel (Kymriah) was approved by U.S. FDA for the treatment of children and young adults with acute lymphoblastic leukemia (ALL). Soon after, on October 18, 2017, FDA granted approval for Axicabtagene ciloleucel (Yescarta) for treating patients with relapsed/refractory diffuse large B-cell lymphoma (r/rDLBCL) and other rare large B-cell lymphomas. Other notable approvals for CAR-T cell therapy products have also been achieved.
In 2018, the European EMA approved Kymriah and Yescarta. Novartis’ Kymriah was given marketing authorization in the EU for the treatment of blood cancers, including B-cell acute lymphoblastic leukaemia (ALL) and relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL). Gilead/Kite Therapeutics’ Yescarta was authorized as a treatment for adult patients with relapsed or refractory DLBCL and primary mediastinal large B-cell lymphoma (PMBCL). Health Canada subsequently approved Kymriah as the first CAR-T therapy in Canada and the Therapeutic Goods Administration (TGA) approved it as the first CAR-T therapy in Australia.
What is CAR-T Cell Therapy?
Chimeric antigen receptors (CARs) are genetically engineered cells that are developed in the laboratory and infused into a patient to help in detecting and fighting cancer. The protein constructs stimulate anti-cancer T-cells, which in turn boost a patient’s immune system. CAR-T cell therapy is defined as a type of immunotherapy that teaches T cells to recognize and destroy cancer.
CAR-T is a type of immunotherapy where doctors collect immune cells, modify them in a laboratory, and provide them the power to easily recognize and kill cancer cells. When infused into a patient, the cells get multiplied and stay in the body as “living drugs.”
How Does CAR-T Cell Therapy Work?
T-cells form the backbone of CAR-T cell therapy. T-cells are the workhorses of our immune system and they play a key role in directing the immune response and killing cells infected by pathogens. In CAR-T cell therapy, blood is drawn from the patient and the T-cells are separated out. In the laboratory, a disarmed virus is used to genetically engineer the T-cells to produce chimeric antigen receptors (CARs) on their surface. These receptors are synthetic and do not exist naturally. Once infused into the patient, these CARs enable the T-cells recognize and get attached to an antigen (specific protein) on the tumor cell leading to the destruction of the tumor.
Two CAR-T products are available in the market. The first one, Kymriah (Tisagenlecleucel) by Novartis, was approved by U.S. FDA in August 2017. It was approved to be used in children and adults with ALL. On May 1, 2018, FDA approved Kymriah for a second indication (diffuse large B-cell lymphoma). The second CAR-T product, Yescarta (Axicabtagene ciloleucel) by Kite Pharmaceuticals, was approved by FDA in October 2017 for patients with lymphoma.
In August 2018, both Kymriah and Yescarta secured approval in Europe, indicating the willingness of European regulators to usher in a new age of regenerative medicine. In September 2018, Health Canada approved Kymriah as the first CAR-T therapy to receive regulatory approval in Canada.
Like all cancer therapies, CAR-T cell therapy can also cause a number of side effects. However, all these side effects can be managed with standard supportive therapies including steroids. The widespread research activities, worldwide clinical trials and treatments in a limited number of U.S. hospitals have created a robust CAR T-cell market with an estimated CAGR of 6.3% per year. This billion dollar market and projected growth would have been not possible without the remarkable efficacy of Kymriah and Yescarta in treating several types of blood cancers.
Market for CAR-T Cell Therapy
CAR-T cell therapy has swept the biotech industry by storm in recent years, creating hope that it could welcome in a new age of cancer treatment. However, the remarkable success stories have come from targeting CD19, which is now considered an antigen that holds the key to a limited range of blood cancers. Presently, this hematological arena is a highly competitive therapy space that is being shared between among leading CAR-T companies.
Scientists, investors and developers invariably agree that the key to longer-term success in this space depends on solving two major problems: identifying antigens other than CD19 that can be targeted with CAR-T therapy with strong efficacy and going beyond liquid cancers into solid tumor indications. CAR-T cell products to deal with solid tumors will undoubtedly offer a larger market potential.
However, it is not an easy task to identify the antigens found on the cells of solid tumors. There are reasons why CD19 is the most common target. It is seen solely on B cells, whose destruction via CAR-T therapy offers a straightforward route for treating B-cell leukemias and lymphomas. At the same time, loss of the body’s B cells is not particularly problematical, because their antibody-producing function can be reinstated by injecting intravenous immunoglobulin (IVIG) to patients.
Currently, the only two non-CD19-directed CAR-T therapies are those that target CD22 in B-cell malignancies and B-cell maturation antigen (BCMA) in multiple myeloma. CD22 is structurally analogous to CD19, while BCMA is an antigen expressed on plasma cells, whose functional loss can also be replaced with IVIG.
The problem with solid tumors is that there is little evidence of CAR-T being able to overcome the numerous difficulties that exist for these to be targeted efficiently. However, both academic and commercial groups are racing against time to identify the antigens on solid tumor cells and develop suitable CAR-T cells, because it represents large market potential.
There are several reasons which make solid tumors difficult to treat using CAR-T cell therapies. Globally, solid tumors outnumber the hematological tumors by 10 to one. In 2015, Novartis and PENN reported that their CART-meso failed to show any effect in patients with mesothelioma, ovarian cancer and pancreatic cancer. Moreover, there was very poor persistence of CAR-T cells in the patients.
The difficulty with solid tumors is that they are usually surrounded by a hostile, immuno-suppressive microenvironment. This environment presents many inhibitory factors that prevent CAR-T cells from reaching them. A typical CAR-T approach will not have success under these conditions. For this reason, Juno and Novartis are engaging in constructing CAR-T cells with novel designs that incorporate additional elements to boost activity within this setting. Currently, these products are in preclinical development.
Driving Forces for the CAR-T Therapy Market
With growing demand for CAR-T therapies, CAR-T companies are proliferating. Growing numbers of these companies are supported by:
Increasing investment flowing into CAR-T cell research
Landmark approvals of CAR-T cell therapies by the U.S. Food & Drug Administration (FDA) and the European Medicines Agency (EMA)
Major acquisitions within the CAR-T industry
Large IPOs within the CAR-T industry
As mentioned, 2017 was the first year that the U.S. FDA approved a CAR-T cell therapy, approving Kymriah in August 2017 and Yescarta in October 2017. Novartis produced Kymriah, a CAR-T therapy used to treat acute lymphoblastic leukemia. Kite Pharma produced Yescarta, a CAR-T therapy to treat adult patients with certain types of large B-cell lymphoma who did not respond to or who relapsed after other kinds of treatment. In August 2018, both Kymriah and Yescarta secured approval in Europe from the EMA.
The approval of these first two CAR-T cell therapies has opened the gates for many other types of cell and gene therapies to claim respect, both from regulators, as well as from the scientific and medical community at large. These historic events demonstrate that CAR-T cell therapy is a market that has emerged, no longer one that is evolving in the future.
CAR-T funding is also on the rise. At first the trend was subtle, but the tide swelled as CAR-T therapies like Kymriah and Yescarta reached the marketplace and created a CAR-T funding craze. CAR-T start-ups have been richly funded by investors eager to get into this trending area of regenerative medicine. Following IPOs by CAR-T players Kite Pharma, Bellicum, Juno Therapeutis and Cellectis totaling over $750 million, CAR-T developer Autolus announced a $150 million IPO. This has bought the total value of recent CAR-T initial public offerings (IPO’s) to approximately $1 billion.
CAR-T Industry Deal-Making
The CAR-T industry has also witnessed aggressive deal-making in recent years. Celgene snagged Juno Therapeutics for a shocking $9 billion in January 2018 and Gilead acquired Kite Pharma for an astounding $11.9 billion in August 2017. After $20 billion of market capitalization from the CAR-T companies in 2018, the CAR-T market has continued to gain momentum.
There have also been more than a dozen CAR-T deals between pharmaceutical companies and academic institutions, with the best known being the partnership between Novartis and the University of Pennsylvania (UPenn). When Kymriah™ because the first CAR-T cell therapy to be approved in the U.S. in August 2017, it resulted from a 5-year collaboration between UPenn and Novartis.
CAR-T financing rounds have also proliferated. In one major example, Celularity raised $250 million in February 2018 to support development of placental-derived products, including T-cells that will be immune advantaged because of their derivation from the placenta. Celularity is looking to burst a major bottleneck in the industry by deriving T-cells from a single (allogeneic) cell line, potentially positioning itself to slash the price point for CAR-T treatments. In other significant example, London-based CAR-T start-up Allogene Therapeutics entered into an asset contribution deal with Pfizer in April 2018, as well as announced a $300 million Series A round.
To better understand and compete within the rapidly expanding CAR-T marketplace, claim this global strategic report to learn the identities and strategies of leading market competitors, access market size data accompanied by market segmentation and forecasts, review clinical trial activity within the sector, assess CAR-T market approvals by region, and importantly, evaluate industry deal-making, emerging technologies, and future directions for the industry at large.
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