The U.S. Food and Drug Administration (FDA) has significantly eased regulations on the 'dream cancer drug' CAR-T cell therapy, intensifying competition among global pharmaceutical corporations. Domestic corporations such as Curocell and AbClon are also analyzing opportunities for expansion overseas.
CAR stands for chimeric antigen receptor. CAR-T, like the chimeras of Greek mythology that have the features of various animals, combines a gene that helps immune cells recognize antigen proteins on the surface of cancer cells with T cells. It targets and attacks only cancer cells, providing superior therapeutic effects while causing fewer side effects. Once administered, it multiplies and continues to kill cancer cells, which is why it is also referred to as a 'living drug' and 'cancer's chain destroyer.'
According to Polaris Market Research & Consulting, a global market research organization, the CAR-T therapy market formed a scale of approximately 10 trillion won last year and is projected to grow to over 15 trillion won this year, reaching more than 256 trillion won by 2034.
◇FDA abolishes CAR-T requirements…global development and investment accelerate
According to industry sources on the 3rd, the FDA has recently completely removed the 'Risk Evaluation and Mitigation Strategy (REMS)' requirements that have been applied to CAR-T cell therapies. REMS is a safety management program that the FDA has specifically required for therapies with significant side effects.
Until now, CAR-T therapies could only be administered at certified hospitals, and certain autoimmune disease treatments, such as 'Actemra (generic name tocilizumab),' had to be available to respond immediately in case of side effects like cytokine release syndrome (CRS) or neurotoxicity, which can cause systemic inflammatory responses.
The analysis is that the FDA abolished these requirements because it determined that the therapeutic effects of CAR-T therapies outweigh the risks of side effects. CAR-T therapies received FDA approval for seven types, starting with Kymriah from Swiss Novartis in 2017 and more recently Aucatzyl from British Autolus Therapeutics last year for treating blood cancers. This decision is expected to facilitate the prescribing of CAR-T therapies.
Regulatory easing is also expected to accelerate the development and investment of CAR-T therapies by global pharmaceutical corporations. AbbVie acquired the U.S. biotech company Capstan Therapeutics for $2.1 billion (3 trillion won) last month, securing the CAR-T candidate CPTX2309.
The company is developing a technology to directly create CAR-T cells inside patients' bodies, instead of the existing method of modifying T cells outside the body and reinjecting them. It delivers mRNA that synthesizes a protein that binds to cancer cells to T cells in the body using nanoparticles that were used in the coronavirus vaccine. The mRNA produces that protein only once and then degrades. In other words, it is a single-use CAR-T cell manufacturing method.
Swiss Roche also acquired the U.S. firm Poseida Therapeutics, known for CAR-T, for $1.5 billion (2 trillion won) last year, and British AstraZeneca purchased IsobioTech, which has a platform for implementing CAR-T technology in the body, for $1 billion (1 trillion won) last March. Bristol Myers Squibb (BMS) also acquired the U.S. company 272 Bio, which is developing CAR-T drugs.
◇Opportunities for domestic latecomer corporations…Curocell and AbClon in the spotlight
These changes could also serve as opportunities for domestic CAR-T therapy developers. Curocell applied for product approval for 'Limcato (Anvalcel),' the first CAR-T blood cancer therapy in Korea, last December.
Limcato is a treatment for a type of blood cancer known as relapsed or refractory large B-cell lymphoma (LBCL). The key is Curocell's self-developed OVIS technology. OVIS simultaneously inhibits PD-1, an immune checkpoint protein that disguises cancer cells as normal cells, along with some T cells and the immune receptor TIGIT found in natural killer (NK) cells. Accordingly, the therapeutic effect is substantial.
Curocell's Limcato was designated as a target under the fast-track processing system for advanced biopharmaceuticals by the Ministry of Food and Drug Safety last August. If designated as such, it can receive approval even by undergoing only phase 2 clinical trials under the 'Advanced Biopharmaceutical Product Approval Review' regulations. The decision regarding Limcato's domestic approval is expected to be made in the second half of this year. The company also plans to challenge the FDA approval.
Previously, Limcato was proven to have a higher efficacy than six approved therapies by the FDA in the final results of the phase 2 clinical trials. The complete remission rate (CR), which is the percentage of patients whose cancers disappeared entirely, was 67.1%, which is higher compared to Kymriah (40%), Breyanzi (53%), and Yescarta (54%).
It also had fewer side effects. The incidence of cytokine release syndrome (CRS) of grade 3 or higher, a typical side effect of cell therapies, was around 9% for Limcato, lower than Kymriah's 17%. Neurotoxicity was also lower for Limcato (3.8%) compared to Kymriah (11%).
AbClon is currently conducting a phase 2 clinical trial for its CAR-T therapy 'Nespecel (AT101),' targeting diffuse large B-cell lymphoma (DLBCL). They plan to apply for rapid approval based on interim results this mid-month.
Kim Geon-soo, CEO of Curocell, noted, 'With the recent easing of CAR-T regulations by the FDA, the possibility of related regulations being eased in Korea in the future is high,' and added, 'As Limcato is expected to expand internationally after receiving approval in Korea, this measure is anticipated to positively influence Curocell's global strategy.'