The global CAR-T market has grown exponentially since the first CAR-T approval reached the market in 2017. Over the past four years, a growing pipeline of CAR-T clinical trials have been accumulating, leading to six global approvals and an explosion of CAR-T market competitors worldwide.
The earliest approvals, Kymriah and Yescarta, have been commercially available since 2017 and 2018, respectively. They’ve been infused into nearly a half million patients worldwide. In July 2020, the U.S. FDA approved a third CAR-T cell therapy, Kite Pharma’s brexucabtagene autoleucel (sold as Tecartus). In February 2021, Breyanzi became the fourth CAR-T approval and the first product with RMAT designation to be licensed by the FDA. In March 2021, the U.S. FDA approved Abecma for the treatment of relapsed or refractory multiple myeloma after four or more prior lines of therapy.
Additionally, JW Therapeutics announced NMPA approval of Relmacabtagene Autoleucel Injection within China in September 2021. This is the first CAR-T product independently developed in China and approved as a Category 1 biologics product, as well as the sixth approved CAR-T product globally.
Autologous vs Allogeneic CAR-T Treatments
All of the approved CAR-T products and nearly 75% of the ongoing clinical trials take an autologous treatment approach. Autologous (self-derived) CAR-T cells are expensive to produce because they are manufactured on a patient-by-patient basis. At times, autologous production can be hampered by a shortage of CAR-T cells or viral vectors. The cost of autologous CAR-T therapy is further escalated by the need for a complex cold chain during transportation. Another key issue is the “vein-to-vein” time or the time that elapses between apheresis and product delivery.
Thus, CAR-T therapies are most often recommended for the end-stage patients who have exhausted all the other treatment options. These challenges drive up the price, making CAR-T therapy unaffordable for a large percentage of patients.
To support the adoption of CAR-T cell therapies, the industry is taking measures to mitigate these challenges. Several CAR-T players have started using efficient gene-transfer tools to impregnate the T cells with CARs. There are numerous examples of partnerships to develop CRISPR and electroporation technologies to modify the T cells. Some companies are also using “on-off” switches that can turn off CAR-T cells to prevent toxicity.
Trends in with the Global CAR-T Market
CAR-T cell therapy has taken the biotech industry by storm, creating hope that it could usher in a new era of cancer treatment. However, the 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 and is being targeted by numerous CAR-T cell therapy competitors.
Scientists, investors, and developers invariably agree that the key to longer-term success in this sector 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 targeted against 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 problematic, because their antibody-producing function can be reinstated by injecting intravenous immunoglobulin (IVIG) to patients.
Unfortunately, the goal of achieving CAR-T success against solid tumors remains elusive thus far, with clinical trials demonstrating a severely limited response. Nonetheless, research is aggressively expanding within this area and the first CAR-T therapy targeted against solid tumors is expected within the coming 5-7 years.
Areas of Active CAR-T Market Investigation
Active areas of investigation in CAR-T market include developing strategies to improve the outcomes of CAR T-cell therapies, minimize toxicities, broaden targets beyond CD19, and target solid tumors. New combination therapies are being explored by many researchers as well. The number of combination therapies under development has been increasing in recent years. It is a challenge to select better preclinical models to identify potential combination therapies. In solid tumors, researchers are focused more on identifying better targets and overcoming obstacles within the tumor microenvironment that block T cell function.
Since 2018, more precise genome editing technologies such as CRISPR have increasingly been used to develop clinical CAR-T product candidates. Allogeneic CAR-T products are yet to reach the market, but hundreds of clinical trials, mostly within China, are now focusing on allogeneic products.
Clinical trials of CAR-modified T cells have produced unprecedented results and are anticipated to have a broader impact as this approach expands into other indications, including other cancers and frontline therapy. The potential for long-term disease control, if fully realized, will have a transformative impact on the field.
CAR-T Cell Therapy, A Game-Changing Technology
Oncologists typically avoid using phrases such as “game changing” or “groundbreaking” when referring to cancer treatments. However, oncologists have surprisingly been referring to CAR-T cell therapies as groundbreaking immunotherapies, because CAR-T therapies offer hope to certain cancer patients where there was none before.
Even though CAR-T therapy has only been approved for a limited range of cancer indications, development of CAR-T treatments for other cancers will occur over time. Over the next three to five years, the global CAR-T market will achieve an estimated two dozen different CAR-T therapies available to treat various types of liquid cancers and eventually solid tumors.
Like the creation of radiation therapy or the bone marrow transplant or the first chemotherapy drugs, CAR-T cell therapy could be the beginning of something spectacular. CAR T-cell therapy involves the collection of lymphocytes or T cells from cancer patients and genetically modifying them within the laboratory. The modified T cells, called CAR-T cells, are armed with a new receptor that makes the T cells potently able to seek and destroy the cancer cells.
Because CAR-T cells are “living drugs”, with a single infusion they can destroy pounds and pounds of tumor cells, multiply themselves in vivo (within the body) and moving from one cancer cell to another until they kill the last tumor cell, resulting in complete remission within the majority of the patients. From 60% to 70% of the patients treated in the earliest clinical trials are now in remission for more than nine years, which is an unprecedented accomplishment.
For the more recently approved therapies, the remission rates have been even more compelling. The clinical trial results of Kymriah, Yescarta, Tecartus, Breyanzi and Abecma have achieved spectacular efficacy in blood cancers, with remission rates upward of 90%.
The Future of the CAR-T Market
The developments within the field of CAR-T cell therapy are only the tip of the iceberg. Today feels similar to the launch of the first chemotherapy treatments, when oncologists started with one type of chemotherapy. Now, fifty years later, cancer patients are being treated with more than 100 different chemotherapy agents.
In a similar way, in the near future we will have several CAR-T therapies available to treat liquid cancers, solid tumors, autoimmune diseases and inflammatory conditions.