In 2017, the U.S. FDA approved two groundbreaking chimeric antigen receptor (CAR) T-cell therapies — Kymriah and Yescarta — to treat acute lymphoblastic leukemia and diffuse large B-cell lymphoma, respectively. These novel therapies utilize a patient’s own immune cells to attack and kill the cancer, and they have shown promise in treating and, in a few cases, “curing” otherwise incurable hematological malignancies.

Despite the breakthrough nature of the clinical data, these first-wave CAR-T 1.0 therapies are struggling to find commercial success, due to factors including:

• Logistic challenges with regard to patients successfully receiving the therapy in approved centers of excellence, and a waiting period of up to four weeks
• Toxicity concerns with administering and receiving the therapy, frequently requiring hospitalization in intensive care
• Burdensome training and accreditation processes
• High cost of overall patient management, coupled with payment and reimbursement challenges
• Manufacturing production issues due to the complex nature of the therapy

Despite these commercial challenges, the clinical promise has helped trigger substantial follow-on research to harness CAR-T to treat other cancers, including multiple myeloma and solid tumors. In keeping with the tremendous excitement for these therapies, investment in a second wave of CAR-T drugs is strong, with more than 270 trials underway and exponential market growth estimated at nearly 50% between 2019 and 2028.

Potential Barriers to CAR-T 2.0 Commercial Success

As this second wave of CAR-T therapies begins coming to market in the next five years, their manufacturers will need to anticipate and prepare to address many of the same commercial challenges as their predecessors, as well as several additional ones, including:

• Capacity constraints: The next CAR-T approval is expected to be for the treatment of relapse and refractory multiple myeloma, a market with an annual incidence of 30,000 new cases every year in the United States alone. Approval for multiple myeloma is likely to result in a substantial increase in requirements for CAR-T administration infrastructure, which, if left unaddressed, could provide a substantial drag on commercial performance.
• Competition among manufacturers: At present, it is unclear if one institute would offer CAR-T therapies from several competitors or if hospitals would have exclusive relationships with a single manufacturer. A preference for exclusivity would be a significant barrier to entry for the new players in the market.
• Competition from other treatments: Unlike CAR-T 1.0 therapies that were approved for patients with no effective treatment options, CAR-T 2.0 therapies are likely to have effective, branded competitors in the marketplace. For instance, in both multiple myeloma and chronic lymphocytic leukemia, several efficacious and off-the-shelf agents are already approved and readily available. In the absence of head-to-head data demonstrating superiority, CAR-T therapies — with all their attendant challenges — risk being reserved for late-line salvage use.
• Competition for patients with community oncologists: With multiple myeloma and chronic lymphocytic leukemia patients being effectively treated in the community, at present community providers are likely to compete for patient ownership. Lack of understanding and familiarity with the treatment, site of administration, and toxicity profile are key factors that could inhibit a widespread adoption of CAR-T therapy among community physicians.
• More payer pushback: Indications like multiple myeloma and chronic lymphocytic leukemia represent much larger patient populations with approved and effective targeted therapies, including some generic ones. As such, CAR-T 2.0 approvals may represent much larger budget impacts than CAR-T 1.0, and they could receive greater payer pushback due to potential restrictions on access and price pressures.