On August 24, Novartis announced that the CD19 CAR-T therapy Kymriah's second-line treatment of aggressive B-cell non-Hodgkin lymphoma (B-NHL) Phase III clinical BELINDA did not meet the primary endpoint EFS. This means that the phase 3 clinical study of BELINDA has failed, and Kymriah's plan to expand the indications to achieve greater volume has failed. Kymriah belongs to the second generation of CAR-T cell therapy, using 4-1BB as a costimulatory binding domain. In 2017, it was first approved by the FDA for the treatment of B-cell acute lymphoblastic leukemia (ALL) that was refractory or relapsed after receiving at least second-line treatment. It was a milestone in the development of cell therapy. Kymriah became the world's first approved CAR- T cell therapy is also the first gene therapy product in the US market; in 2018, it received the second indication for relapsed or refractory large B-cell lymphoma. Since Kymriah went public, Novartis has regarded it as a key driving force for future performance growth. According to the financial report, global sales in 2020 will be US$474 million, an increase of 68% year-on-year.
Image source: Yaozhi Data
It is worth mentioning that Novartis has long regarded the expansion of Kymriah indications as the key to achieving its CAR-T ambitions. The failure of the second-line B-NHL clinical failure study undoubtedly weakened its expansion in CAR-T. Competitive strength in the field of disease treatment.
Novartis CAR-T therapy second-line NHL breaks down, Gilead and Bristol-Myers Squibb take advantage of the trend
According to statistics from Yaozhi data, there are currently 6 CAR-T cell therapies approved for marketing in the world, namely Novartis’ Kymriah, Gilead’s Yescarta and Tecartus, Bristol-Myers (BMS)’s Breyanzi and Abecma, and China’s first in June The approved CAR-T cell therapy Fosun Kate’s Akirensai injection.
Overview of Global CAR-T Therapy Approval
Data source: Yaozhi data
However, compared to Kymriah’s frustrating clinical trial news, Kymriah’s direct competitors, Gilead’s Yescarta and Bristol-Myers Squibb’s Breyanzi, have won the second-line treatment B-NHL study. The top-line results of the ZUMA-7 trial of Yescarta for second-line treatment of patients with relapsed or refractory large B-cell lymphoma (LBCL) show superiority compared with the current standard of care (SOC) for LBCL patients; Breyanzi is in line with stem cell transplantation Among eligible R/R LBCL patients, Breyanzi has significant efficacy compared with current standard care regimens including high-dose chemotherapy [HDCT] and hematopoietic stem cell transplantation [HSCT]. It is reported that LBCL patients have a poor prognosis. In the era of rituximab-based immunochemotherapy, about 40% of LBCL patients cannot achieve long-term disease-free survival and require second-line treatment. Therefore, CAR-T drugs are effective in second-line treatment. The therapeutic effect will open up a larger market for CAR-T therapy. According to Gilead’s report, Brian Abrahams, an analyst at RBC Capital Markets, predicted that Yescarta’s peak sales of second-line treatments are expected to reach US$622 million, almost two of the peak sales of third-line treatments. Times. It is also worth noting that Breyanzi was only approved for marketing in February this year for the treatment of adult patients with relapsed/refractory LBCL who have received two or more systemic treatments. The proportion of CD4-positive T cells is controlled, so that the side effects of cell therapy can be better controlled; now Novartis has encountered obstacles in its efforts to transfer Kymriah to the early B-NHL treatment line, and Breyanzi (lisocabtagene maraleucel) is in a phase 3 clinical trial The results of the primary and key secondary endpoints showed that compared with standard treatment, it significantly improved the event-free survival, complete remission rate and progression-free survival of patients with relapsed/refractory large B-cell lymphoma (LBCL); Compared with the standard second-line treatment, whether the advantages of a therapy that show clinical benefits can take advantage of the situation, it remains to be seen! Although Kymriah seems unable to use second-line B-cell lymphoma, the drug is still expected to expand to third-line follicular lymphoma. According to the results recently announced at the annual meeting of the American Society of Clinical Oncology, data from the ELARA trial showed that Kymriah completely cleared signs of cancer in 66% of previously treated patients, and 86% of patients responded. However, this also has to compete head-on with Yescarta. According to recent trial data released by Gilead, Yescarta has a total remission rate of 94% in the treatment of follicular lymphoma. According to financial reports, Yescarta's sales in the first half of 2021 reached 338 million U.S. dollars, leading the CD19 CAR-T field; Kymriah had sales of 298 million U.S. dollars last year. Facing the failure of second-line B-NHL clinical research and the slightly weaker third-line follicular lymphoma data, whether Kymriah can rise and continue to promote Novartis’s performance growth, wait and see. CAR-T therapy research "blowout", the country is gradually entering the harvest period CAR-T therapy is considered to be one of the most promising cancer treatments, and its launch has opened a new milestone in the history of human anti-cancer. At the same time, it has also triggered an upsurge in cell therapy research and development. According to a previous report by Nature Reviews Drug Discovery, CAR-T occupies a leading position in the global cell therapy drug research and development pipeline. According to statistics, as of the end of June, a total of 670 CAR-T clinical trials are ongoing worldwide, and China and the United States account for approximately 91.3% of the world. Among them, the number of CAR-T clinical trials in China has shown a "blowout" since 2016. The number of domestic CAR-T clinical trials registered on Clinicaltrials has exceeded 365, ranking first in the world, accounting for 53.3%. At the same time, CAR-T is considered to be one of the most promising areas for domestic companies to keep up with the global R&D pace. At present, Fosun Kate’s Achilles injection has been approved for marketing. Combined antigen receptor (CAR) T cell therapy relma-cel injection as a new drug for the third-line therapy of relapsed or refractory B-cell lymphoma has been approved for marketing, or it will become the second domestic CAR- T therapy.
Overview of domestic enterprise CAR-T layout and research progress
Data source: Yaozhi data, corporate announcements and other public data
Note: The above data is manually searched and sorted out. If there is any omission, please leave a message to add and discuss! Reference: Novartis' Kymriah flops in earlier lymphoma use, where Gilead, Bristol Myers CAR-T rivals succeeded
August 26, 2021
