KITE’S YESCARTA® (AXICABTAGENE CILOLEUCEL) FIRST CAR T-CELL THERAPY TO RECEIVE EUROPEAN MARKETING AUTHORISATION FOR USE IN SECOND-LINE DIFFUSE LARGE B-CELL LYMPHOMA AND HIGH-GRADE B-CELL LYMPHOMA

-- First Treatment in 30 Years to Improve Upon Standard of Care (SOC) for Second-Line Treatment of DLBCL --

-- Based on Landmark ZUMA-7 Study, Patients with DLBCL Treated Second-Line with Axicabtagene Ciloleucel Had Event-Free Survival of 8.3 Months versus Two Months for SOC [4-fold greater improvement] --

-- In ZUMA-7, Axicabtagene Ciloleucel Patients with DLBCL were 2.5 Times More Likely than SOC to be Alive at Two Years Without Cancer Progression or Need for Additional Treatments --

Stockley Park, UK – 17 October, 2022 – Kite, a Gilead Company, today announces that the European Commission (EC) has granted approval for the use of Yescarta^® (axicabtagene ciloleucel) for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) who relapse within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy. The approval is based on results from the pivotal Phase 3 ZUMA-7 study, the largest and longest trial of a CAR T-cell therapy versus SOC in this patient population. Axicabtagene ciloleucel is now the first Chimeric Antigen Receptor (CAR) T-cell therapy approved for patients in Europe who do not respond to first-line treatment. This provides an important additional treatment option for the most common form of non-Hodgkin lymphoma. Although 60% of newly diagnosed LBCL patients, including those with DLBCL, will respond to their initial treatment, 40% will relapse or will not respond and need second-line treatment.[1]^,[2]

“We are very proud to announce Kite’s fifth approved indication in Europe in our continued commitment to the research and delivery of cell therapies with curative potential to patients who might benefit around the world,” said Christi Shaw, CEO, Kite. “Today’s approval marks an important step towards that goal by providing patients in Europe this option of CAR T-cell therapy earlier in their treatment journey.”  

SOC therapy for this patient population has historically been a multi-step process expected to end with a stem cell transplant. The process starts with chemoimmunotherapy, and if a patient responds to and can tolerate further treatment, they move on to high-dose chemotherapy (HDT) followed by a stem cell transplant (ASCT).

“This approval marks a major shift in the treatment of LBCL when initial treatment has failed. In ZUMA-7, treatment with axicabtagene ciloleucel resulted in an overall better outcome for patients than standard of care, especially in terms of event-free survival, marking a new era for treatment earlier in the disease pathway for more patients,” said Professor John Gribben, Professor of Medical Oncology at the Cancer Research UK Barts Centre, London. “The ZUMA-7 data has also broadened our understanding of this CAR T-cell therapy, allowing us to better manage or prevent side-effects, which is important as it moves earlier in the treatment pathway and for older patients and those with medical conditions for whom the standard of care might have been difficult.”

The ZUMA-7 study, demonstrated that at a median follow-up of two years, axicabtagene ciloleucel-treated patients had a four-fold greater improvement in the primary endpoint of event-free survival (EFS; hazard ratio 0.40; 95% CI: 0.31-0.51, P<0.001) over the current SOC (8.3 months vs 2.0 months). Additionally, axicabtagene ciloleucel demonstrated a 2.5 fold increase in patients who were alive at two years without disease progression or need for additional cancer treatment vs SOC (41% v 16%). Improvements in EFS with axicabtagene ciloleucel were 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]), high-grade B-cell lymphoma (HR: 0.28 [95% CI: 0.14-0.59]), and double-expressor lymphoma patients (HR: 0.42 [95% CI: 0.27-0.67]).[3]

In the ZUMA-7 trial, axicabtagene ciloleucel had a safety profile that was consistent with previous studies. Among the 170 axicabtagene ciloleucel-treated patients evaluable for safety, Grade ≥3 cytokine release syndrome (CRS) and neurologic events were observed in 6% and 21% of patients, respectively. No Grade 5 CRS or neurologic events occurred. In the SOC arm, 83% of patients had Grade ≥3 events, mostly cytopenias (low blood counts).³

About ZUMA-7

ZUMA-7 is an ongoing, randomised, open-label, global, multicentre (US, Australia, Canada, Europe, Israel) Phase 3 study of 359 patients at 77 centres, evaluating the safety and efficacy of a single-infusion of axicabtagene ciloleucel versus current SOC for second-line therapy (platinum-based salvage combination chemotherapy regimen followed by high-dose chemotherapy and autologous stem cell transplant in those who respond to salvage chemotherapy) in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. The primary endpoint is event free survival (EFS). Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes and safety.³

In the analysis of patient reported outcomes (PROs) patients receiving axicabtagene ciloleucel and eligible for the PROs portion of the study (n=165), showed statistically significant improvements in Quality of Life (QoL) at Day 100 compared with those who received SOC (n=131), using a pre-specified analysis for three PRO-domains (EORTC QLQ-C30 Physical Functioning, EORTC QLQ-C30 Global Health Status/QOL, and EQ-5D-5L visual analogue scale [VAS]). There was also a trend toward faster recovery to baseline QoL in the axicabtagene ciloleucel arm versus SOC.[4]

About Diffuse Large B-Cell Lymphoma and High-Grade B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common sub-type of non-Hodgkin lymphoma (NHL), representing around 30% of cases.¹ High-grade B-cell lymphoma (HGBL) is a recently introduced, rare subset of LBCL marked by aggressive B-cell lymphomas including tumours with Burkitt-like or blastoid tumours without double-hit characteristics. In Europe it is estimated that up to 38,000 new cases of LBCL were diagnosed in 2020. Although first-line treatment can be effective in around 60% of cases, 40% will relapse or not respond and need second-line treatment. For people who relapse, or who do not respond to first-line treatment, outcomes are often poor.³ Most patients with refractory (no response) LBCL have no curative treatment options.

About Axicabtagene Ciloleucel

In August 2018, axicabtagene ciloleucel, a chimeric antigen receptor (CAR) T-cell therapy, received European Marketing Authorisation for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B cell lymphoma (PMBCL), after two or more lines of systemic therapy. In June 2022, axicabtagene ciloleucel was granted European Marketing Authorisation for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after three or more lines of systemic therapy.[5]

About Kite

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, with manufacturing operations in North America and Europe. Kite’s singular focus is cell therapy to treat and potentially cure cancer. As the cell therapy leader, Kite has more approved CAR T indications to help more patients than any other company. 

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavourable results from ongoing and additional clinical trials, including those involving axicabtagene ciloleucel; uncertainties relating to regulatory applications and related filing and approval timelines; the risk that physicians may not see the benefits of prescribing axicabtagene ciloleucel for the treatment of LBCL; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2022 as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements.

[1] Leukemia & Lymphoma Society. NHL subtypes. Available at: https://www.lls.org/lymphoma/non-hodgkin-lymphoma/nhl-subtypes Accessed: September 2022.

[2] Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study [published correction appears in Blood. 2018 Feb 1;131(5):587-588]. Blood. 2017;130(16):1800-1808. doi:10.1182/blood-2017-03-769620.

[3] Locke, F.L., Miklos, D.B. et al. (2022) ‘Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma’, N Eng J Med, 386(7), 640-654.

[4] Elsawy, M., Chavez, J.C., Avivi I., et al. (2022) ‘Patient-reported outcomes in ZUMA-7, a phase 3 study of axicabtagene ciloleucel in second-line large B-cell lymphoma’, Blood, 2022015478. doi: 10.1182/blood.2022015478. Epub ahead of print. PMID: 35839452.

^[5] European Medicines Agency, Yescarta® (axicabtagene ciloleucel) SmPC. Available at: https://www.ema.europa.eu/documents/product-information/yescarta-epar-product-information_en.pdf (Accessed: September 2022).