CAR-T PROGRESS IN CHINA
trials that led to Carvykti’s approval in the US, says the initial impressive efficacy data with Carvykti from China has been instructive for ongoing studies in the US that are now exploring it in earlier lines of treatment. Although China has more CAR-Ts in the pipeline, so far its regulatory agency, the National Medical Products Administration (NMPA), has approved only two CAR-T therapies: Gilead’s Yescarta, which was co-developed with FosunKite for the China market, and JW Therapeutics’ relmacabtagene autoleucel injection or relma-cel, which became the second approved therapy in September 2021. Even though the two NMPA-approved CAR-T
therapies are not yet covered by major insurance in China, a couple of hundred patients have already received these drugs through private funding or outcome-based reimbursement schemes with the individual company, Lu says. Relma-cel is an indigenously produced CAR-T and is likely to be included in the next National Reimbursement Drug List (NRDL) update since indigenous therapies were favoured over drugs from international companies, says Sahu. Particularly in the case of CAR-Ts, which are personalised therapies, Deere says it would be difficult “for multinational companies to compete with domestic Chinese companies, not only because of the cultural and linguistic factors”, but also because the government is going to likely prefer national companies.
CAR-T focus evolves Current research trends validate the research interests and wins in the CAR-T field in the past 10 years. While initial CAR-T therapies were personalised autologous therapies directed towards the CD19 antigen in relatively rare blood cancers, subsequent development has branched out to allogeneic or off-the-shelf therapies in several cancer types. In line with the initial approvals, in both the US and China, the most common indication for which CAR-T drugs have been developed is a blood cancer. In fact, 60% of CAR-T drugs developed by Chinese companies and 55% of US CAR-T drugs have blood cancer as a listed indication. CAR-T therapies need a target antigen that is ubiquitously, and ideally exclusively, expressed in a tumour, which is the case with haematological cancers. As such, developing this modality in solid
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“One potential reason for the drop in CAR-T research can also be attributed to the rise of effective bispecific antibodies”
tumours has been and continues to be challenging. Still, since the initial successes in ALL and B cell lymphomas, the focus on CAR-T therapies in the US is slowly shifting towards solid tumours, with 21% of the CAR-T therapies being designed against solid tumours. In China, however, this does not appear to be the case yet, with only 9% of all CAR-Ts being developed in solid tumours. One potential reason for the drop in CAR-T
research can also be attributed to the rise of effective bispecific antibodies. Often looked at as “poor man’s CAR-Ts”, Parekh says these offer an off-the-shelf alternative that can compete with CAR-Ts and potentially even leapfrog them. So far, efficacy signals have been encouraging, and these antibodies could also be used more easily in smaller community hospitals, he adds.
Research continues despite the pandemic Despite the disruptive impact of COVID-19 on trials worldwide, trials, in general, have continued in China, and this is the case with CAR-T therapies as well. Dr Lu says her hospital recruited 272 patients in different CAR-T trials in 2019, which increased to 329 patients in 2020, and 394 patients last year. Participating in a trial also allows patients to access expensive CAR-Ts without having to pay from their pockets, which in addition to the encouraging efficacy results in certain cancers has incentivised participation. In the US, while things are now picking up,
Parekh says a lot of academic centres are facing shortages of skilled researchers following the pandemic. Recent lockdown restrictions in line with China’s Zero COVID policy have made trial site visits difficult at times. But Lu points out that lockdown policies usually last for a few days to a month and are specific to a particular location only. Moreover, preclinical CAR-T research has continued during this time. Given the results seen with CAR-T therapies, especially in cases where it’s a life-or-death situation, patients are willing to make every effort to join a clinical trial, says Lu.
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