Kite’s CAR-T Therapy Yescarta Receives Positive CHMP Opinion for Second-Line Treatment of DLBCL and HGBL in Europe

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News date: September 22, 2022 / BIOON BioValley -- Kite Pharma, a T-cell therapy company under Gilead Sciences, recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending 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 or relapse within 12 months after first-line chemoimmunotherapy。

The European Commission (EC) will review the CHMP opinion and is expected to make a final decision in the coming months. If approved,Yescarta will become the first CAR-T cell therapy in Europe for patients with DLBCL and HGBL who are ineffective with first-line treatment.

In April this year, 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 first-line chemoimmunotherapy. This approval makesYescarta Becomes 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 YearsAlthough 60% of patients with newly diagnosed LBCL will respond to initial treatment, 40% of patients will relapse or fail to respond and require second-line treatment.

Marie Jose Kersten, Professor of Hematology at the Amsterdam University Medical Center, commented: "The prognosis for patients with DLBCL and HGBL who are refractory to or relapse early after first-line treatment is often very poor, with limited treatment options. If approved, Yescarta has the potential to provide a new standard of care for patients with relapsed or refractory DLBCL and HGBL. Importantly, in randomized Phase 3 clinical trials,Compared with the current standard of care, patients receiving Yescarta treatment also showed significant improvement in quality of life.。”

The positive review opinion of the CHMP is based on the results of the milestone Phase 3 ZUMA-7 study. ZUMA-7 is the world's first, largest, and longest-follow-up clinical trial comparing CAR-T with the current standard of care (SOC) second-line treatment adopted over the past few decades. 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. It compared a single infusion of Yescarta with the current SOC second-line treatment (administering a platinum-containing salvage combination chemoimmunotherapy regimen, followed by high-dose chemotherapy [HDT] and autologous hematopoietic stem cell transplantation [ASCT] for patients who responded 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). Furthermore, the proportion of patients who were alive and free from disease progression or 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,Yescarta treatment demonstrated consistent EFS improvement 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 controllable and consistent with previous studies.

Yescarta (Axicabtagene Ciloleucel, Axi-Cel) is a CD19-directed autologous CAR-T cell therapy acquired by Gilead Sciences for $11.9 billion through the acquisition 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, used to treat adult patients with relapsed or refractory large B-cell lymphoma after receiving second-line or later 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 alsoThe first CAR-T cell therapy product officially approved for marketing by the National Medical Products Administration (NMPA)As a novel cancer treatment, Axicabtagene Ciloleucel Injection (Yikaida) has brought new hope and opportunities to patients with relapsed or refractory large B-cell lymphoma in China who have received two or more lines of systemic therapy. (Bioon.com)

Source: Kite’s CAR T-cell Therapy Yescarta® First in Europe to Receive Positive CHMP Opinion for Use in Second-line Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma