Gilead's Yescarta Becomes First CAR-T Therapy Approved in EU for Second-Line Treatment of DLBCL and HGBL

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October 25, 2022 /BIOON/ -- Kite Pharma, a T cell therapy company under Gilead Sciences, recently announced that the European Commission (EC) has granted approval.CD19 CAR-T Cell Therapy Yescarta (axicabtagene ciloleucel): For Second-Line Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) and High-Grade B-Cell Lymphoma (HGBL). The specific population is:Adult patients with DLBCL and HGBL who are refractory to first-line chemoimmunotherapy or relapse within 12 months after completing first-line chemoimmunotherapy. It is worth mentioning that,Yescarta is the first CAR-T cell therapy approved in Europe for patients with DLBCL and HGBL who are ineligible for first-line treatment, marking the first therapy superior to standard care in nearly 30 years., will provide an important additional treatment option for the most common type of non-Hodgkin lymphoma (NHL).

For patients with DLBCL and HGBL who are refractory to or relapse early after first-line treatment, the prognosis is often poor with limited treatment options. Yescarta will provide a new standard of care for patients with relapsed or refractory DLBCL and HGBL. Importantly,In the randomized Phase 3 clinical trial, patients receiving Yescarta showed significant improvement in quality of life compared to the current standard of care.

In April 2022, Yescarta received approval from the U.S. FDA for the treatment of adult patients with large B-cell lymphoma (LBCL) who are refractory to first-line chemoimmunotherapy or relapse within 12 months after completing first-line chemoimmunotherapy. This approval makes Yescarta the world's first CAR-T cell therapy for second-line treatment of LBCL, marking the first therapy superior to standard care in nearly 30 years.

Although 60% of patients with newly diagnosed LBCL respond to initial treatment, 40% of patients relapse or fail to respond and require second-line treatment.For these patients, the standard of care (SOC) treatment has historically been a multi-step process, expected to culminate in stem cell transplantation. This process begins with chemoimmunotherapy, and if the patient responds to further treatment and can tolerate it, moves on to high-dose chemotherapy (HDT), followed by autologous hematopoietic stem cell transplantation (ASCT).

This EU approval is based on the results of the landmark Phase 3 ZUMA-7 study. ZUMA-7 is the world’s first, largest, and longest-follow-up clinical trial comparing CAR-T therapy with the current standard of care (SOC) that has been used for decades as a second-line treatment. This is a randomized, open-label, global, multicenter Phase 3 study conducted in adult patients with relapsed or refractory LBCL within 12 months after first-line chemoimmunotherapy. The study compared a single infusion of Yescarta with the current SOC second-line treatment (a platinum-based salvage combination chemoimmunotherapy regimen, followed by high-dose chemotherapy [HDT] and autologous hematopoietic stem cell transplantation [ASCT] for patients responding to salvage chemotherapy).

The results showed,In terms of the primary endpoint of event-free survival (EFS), Yescarta demonstrated a clinically meaningful and statistically significant improvement compared to the current standard-of-care (SOC) second-line treatment used over the past few decades (HR=0.40; 95% CI: 0.31-0.51; p<0.001).EFS is defined as the time from randomization to the earliest date of disease progression, initiation of new lymphoma treatment, or death from any cause.The median EFS in the Yescarta treatment group was four times that of the SOC group (8.3 months vs 2.0 months). Additionally, the proportion of patients alive and free from disease progression or not requiring additional cancer treatment after two years was 2.5 times higher in the Yescarta group than in the SOC group (40.5% vs 16.3%).

Subgroup analysis showed that the EFS improvement demonstrated with Yescarta was consistent across key patient subgroups, including: elderly patients (HR=0.28 [95% CI: 0.16-0.46]), primary refractory patients (HR: 0.43 [95% CI: 0.32-0.57]), patients with high-grade B-cell lymphoma including double-hit and triple-hit lymphomas (HGBL; HR=0.28 [95% CI: 0.14-0.59]), and double-expressor lymphoma patients (HR=0.42 [95% CI: 0.27-0.67]).

Patient-Reported Outcome (PRO) analysis showed,Compared with patients receiving SOC treatment, patients receiving Yescarta treatment showed a statistically significant improvement in quality of life (QoL) on Day 100. The Yescarta group exhibited a trend toward faster recovery to pre-treatment (baseline) QoL compared with the SOC group.In the ZUMA-7 trial, the safety of Yescarta was manageable and consistent with previous studies.

Professor John Gribben, Professor of Medical Oncology at the Barts Cancer Institute in London, UK, commented: "This approval marks a significant shift in the treatment of LBCL after initial therapy fails. In the ZUMA-7 trial, Yescarta demonstrated overall superior efficacy compared to standard care, particularly in event-free survival, heralding a new era for earlier treatment of the disease in more patients. The ZUMA-7 trial data also expand our understanding of CAR-T cell therapy, enabling us to better manage or prevent side effects. This is particularly important as Yescarta moves earlier in the treatment pathway, and for elderly patients and those in poor health who are difficult to treat with standard care therapies."

Yescarta (Axicabtagene Ciloleucel, Axi-Cel) is a CD19-directed autologous CAR-T cell therapy., acquired by Gilead for a hefty $11.9 billion through the purchase of Kite Pharma. To date, Yescarta has been approved for three indications in the United States: (1) Treatment of adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) within 12 months after first-line chemoimmunotherapy. (2) Adult patients with relapsed or refractory LBCL who have received at least two prior systemic therapies, including diffuse large B-cell lymphoma not otherwise specified (DLBCL), primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma (Yescarta is not indicated for the treatment of primary central nervous system lymphoma). (3) Adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

In China, in June 2021, the National Medical Products Administration (NMPA) approved FOSUN Kite's axicabtagene ciloleucel injection (trade name: Yikaida) for marketing through the priority review and approval process. This drug is the first cell therapy product to be approved for marketing in China and is used to treat adult patients with relapsed or refractory large B-cell lymphoma who have received two or more lines of systemic therapy (including diffuse large B-cell lymphoma not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and diffuse large B-cell lymphoma transformed from follicular lymphoma).

Axicabtagene Ciloleucel Injection (Yikaida) is a product based on Kite Pharma's Yescarta (Axicabtagene Ciloleucel, Axi-Cel), which has undergone technology transfer and is planned for localized production within China (excluding Hong Kong, Macao, and Taiwan).This product was introduced by Fosun Kite from Kite Pharma and has obtained the technical and commercialization rights in mainland China, the Hong Kong Special Administrative Region, and the Macao Special Administrative Region.

This product is the first CAR-T cell therapy product that Fosun Kite has advanced to commercialization in China, and it is also the first CAR-T cell therapy product formally approved for marketing by the National Medical Products Administration (NMPA). As a completely new method for cancer treatment, Axicabtagene Ciloleucel Injection (Yikaida) has brought renewed hope and opportunities to patients with relapsed or refractory large B-cell lymphoma in China who have received second-line or higher systemic treatments. (Bioon.com)

Source: Kite’s Yescarta First CAR T-cell Therapy to Receive European Marketing Authorization for Use in Second-Line Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma