Daiichi Sankyo Authorizes First Yescarta Treatment Site in Japan

Kite’s Yescarta will finally be available to patients in Japan, after Kite’s partner Daiichi Sankyo authorized the first treatment site for the CAR T-cell therapy in Japan on Thursday. This ends a near year-long wait for access to Yescarta in the country, after it was approved in January. 

The treatment center will cover patients with relapsed or refractory large B-cell lymphomas (LBCL). Yescarta, a.k.a. axicabtagene ciloleucel or axi-cel, is a FDA-approved CD19 CAR T-cell therapy for multiple forms of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, transformed follicular lymphoma or high-grade B-cell lymphoma. 

“We are pleased to bring the benefits of axicabtagene ciloleucel to eligible patients in Japan, in collaboration with Daiichi Sankyo,” said Warner Biddle, Kite’s commercial head. “Japan has the second-largest number of people diagnosed with non-Hodgkin lymphoma globally and we remain committed to bringing our innovative CAR T-cell therapies to additional new markets.”

Both companies have also agreed to broaden their business collaboration over the marketing of Yescarta in Japan. Daiichi Sankyo currently holds the rights to develop, manufacture and sell the drug in Japan, after an agreement with Kite, a Gilead company, in 2017. 

Qualifying for CAR T 

The making and provision of CAR T-cell therapies is a complex task. Hospitals must be rigorously trained in handling the immunotherapy to minimize risks and ensure patient safety. 

Additionally, several factors are taken into account when qualifying a hospital. These include the hospital’s specializations and services, geographic coverage, and experience in handling difficult procedures like stem cell transplantation. A co-located intensive care unit is another important consideration, as cytokine release syndrome (CRS) is a common and severe side effect of CAR T-cell therapies. 

Furthermore, Yescarta is only available to patients who have: never received a CD19 CAR T-cell infusion, have been treated with two or more lines of treatment including chemotherapy or autologous stem cell transplant, and are ineligible for autologous stem cell transplant. 

Yescarta’s Approval Based on Two Trials

The January approval of Yescarta was based on the results from a global pivotal trial (Zuma-1) conducted by Kite and a Phase 2 by Daiichi Sankyo in Japan. The Japan Phase 2 reached its primary endpoint after it reported an objective response rate of 86.7%. 

The safety profile of the drug was also consistent with that observed in Zuma-1. The most common side effects were low immune cell and platelet counts in the blood and CRS. 

CAR T-cell Therapies in Japan and Changes in DLBCL Treatment

Yescarta was the second CAR T-cell therapy to get the greenlight in Japan, after the approval of Novartis’ Kymriah (tisagenlecleucel) in 2019. A third approval in the area was given Bristol-Myers Squibb’s Breyanzi (lisocabtagene maraleucel or liso-cel) in March. 

Earlier in December, Janssen and Legend Biotech filed for approval of their own CAR T-cell therapy, ciltacabtagene autoleucel (cilta-cel) to treat multiple myeloma. 

CAR T-cell therapies are typically reserved as third-line or later treatments for DLBCL, but recent clinical trials are suggesting that these immunotherapies may work as second-line or earlier treatments. 

The latest results of the Phase 3 Zuma-7 trial on axi-cel, presented at 63rd American Society of Hematology (ASH) Annual Meeting 2021, has shown that the drug improved event-free survival (where disease did not progress and the patient did not start a new therapy) by 60% over the standard of care in patients with second-line LBCL. The standard of care for patients in this disease setting involves chemo followed by stem cell transplant. 

Also presented at ASH 2021 was BMS’s Phase 3 Transform trial of liso-cel, which demonstrated that the drug, used as a second-line treatment for LBCL, cut the risk of EFS complication by 65.1% over the standard of care. Patients also reported improved quality of life after second-line treatment with liso-cel versus standard of care. 

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Joy Lin

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