KITE’S YESCARTA® (AXICABTAGENE CILOLEUCEL) CAR T-CELL THERAPY DEMONSTRATES A STATISTICALLY SIGNIFICANT IMPROVEMENT IN OVERALL SURVIVAL FOR INITIAL TREATMENT OF RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (LBCL)

--  First and Only Treatment in Nearly 30 Years to Show Statistically Significant Improvement in Overall Survival (OS) for Initial Treatment of R/R LBCL Patients Versus Historical Standard of Care in Curative Setting --

-- Landmark ZUMA-7 Study OS Data Reach Maturity Per Protocol, 5 Years After 1^st Patient Randomised --

Stockley Park, UK – 21 March 2023 – Kite, a Gilead Company, today announced the primary overall survival (OS) analysis results of the Phase 3 ZUMA-7 study. The results showed a statistically significant improvement for Yescarta^® (axicabtagene ciloleucel) in OS versus historical treatment, which was the standard of care (SOC) in a curative setting for nearly 30 years, for initial treatment in adult patients with relapsed/refractory large B-cell lymphoma (R/R LBCL) within 12 months of completion of first-line therapy. Historical SOC is a multi-step process involving platinum-based salvage combination chemoimmunotherapy regimen followed by high-dose therapy (HDT) and autologous stem cell transplant (ASCT) in those who respond to salvage chemotherapy. These findings will be presented in full later this year at an upcoming scientific meeting.

Overall survival was designated as a clinically important prespecified key secondary endpoint, defined as the length of time from randomisation to death from any cause.[1] ZUMA-7 was conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA) whereby the trial design, clinical endpoints and statistical analysis were agreed upon in advance with the Agency. This pre-specified analysis was also agreed by other health authorities.

ZUMA-7 is considered a landmark trial as the first and largest Phase 3 study of any CAR T-cell therapy, with the longest follow-up, which has demonstrated event-free survival (EFS), the primary endpoint, that is superior to historical SOC treatment.  Data from the pivotal ZUMA-7 trial supported the European Commission approval of axicabtagene ciloleucel in October 2022 for the treatment of adult patients with diffuse large B-cell lymphoma and high-grade B-cell lymphoma who relapse within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy.[2]  The European approval followed the U.S. approval for initial treatment of R/R LBCL in April 2022, followed by approvals in a number of other countries such as Great Britain, Israel, Japan, and Switzerland.

About ZUMA-7 Study

ZUMA-7 is a randomised, open-label, global, multicentre, Phase 3 study evaluating the safety and efficacy of axicabtagene ciloleucel versus SOC for initial treatment in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy.  In the study, 359 patients in 77 centres around the world were randomised (1:1) to receive a single infusion of axicabtagene ciloleucel or historical SOC second-line treatment. The primary endpoint is EFS as determined by blinded central review and defined as the time from randomisation to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes (PROs) and safety. Per hierarchical testing of primary and key secondary endpoints and group sequential testing of OS, an interim analysis of OS occurred at the time of the primary EFS analysis. The prespecified primary OS analysis was to be conducted after 210 deaths or no later than five years after the first patient was randomised.^[1]

Axicabtagene ciloleucel demonstrated a 2.5-fold increase in patients who were alive at two years and did not experience cancer progression or require the need for additional cancer treatment (40.5% vs. 16.3%) and a four-fold greater median EFS (8.3 mo. vs. 2.0 mo.) compared to SOC (hazard ratio 0.398; [95% CI: 0.308-0.514, P<0.0001]). In addition, ZUMA-7 study participants on the axicabtagene ciloleucel arm did not receive additional bridging chemotherapy that could have potentially confounded results.[3]

Nearly three times as many patients randomised to axicabtagene ciloleucel ultimately received the definitive CAR T-cell therapy treatment (94%) versus those randomised to SOC (35%) who received on-protocol HDT+ASCT. More patients responded to axicabtagene ciloleucel (ORR: 83% vs. 50%, odds ratio: 5.31 [95% CI: 3.1-8.9; P<0.0001]) and achieved a complete response (CR) with axicabtagene ciloleucel (CR rate: 65% vs. 32%) than with SOC. At  the time of the primary EFS analysis, more than half of patients in the SOC arm subsequently received axicabtagene ciloleucel off study.^[3]

In the study, axicabtagene ciloleucel had a safety profile that was consistent with previous studies. Among the 168 axicabtagene ciloleucel-treated patients evaluable for safety, Grade ≥3 cytokine release syndrome (CRS) and neurologic events were observed in 7% and 25% of patients, respectively. In the SOC arm, 83% of patients had high grade events, mostly cytopenias (low blood counts).^[3]

About Axicabtagene Ciloleucel

In October 2022, axicabtagene ciloleucel, a chimeric antigen receptor (CAR) T-cell therapy, was approved by the European Commission (EC) 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.² In June 2022, axicabtagene ciloleucel was approved by the EC for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after three or more lines of systemic therapy. In August 2018, axicabtagene ciloleucel was approved by the EC 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.^[2]

About Large B-Cell Lymphoma (LBCL)

LBCL is the most common sub-type of non-Hodgkin lymphoma (NHL), representing around 31% of cases.[4] In Europe it is estimated that up to 38,000 new cases of LBCL were diagnosed in 2020.[5] Although first-line treatment can be effective in around 60% of cases, up to half of these will relapse (return).[6]^,[7] For people who relapse, or who do not respond to first-line treatment, outcomes are often poor.⁷ Most patients with refractory (no response) LBCL have no curative treatment options.[8]

About Kite 

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on cell therapy to treat and potentially cure cancer. As the global cell therapy leader, Kite has treated more patients with CAR T-cell therapy than any other company.  Kite has the largest in-house cell therapy manufacturing network in the world, spanning process development, vector manufacturing, clinical trial production and commercial product manufacturing.

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. Gilead Sciences acquired Kite in 2017.

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 Gilead and Kite’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving axicabtagene ciloleucel; Gilead and Kite’s ability to receive regulatory approvals in a timely manner or at all, including additional regulatory approvals of axicabtagene ciloleucel, and the risk that any such approvals may be subject to significant limitations on use; the risk that physicians may not see the potential benefit of prescribing axicabtagene ciloleucel as an initial treatment for R/R LBCL and for other indications; 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-K for the quarter ended December 31, 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. Investors are 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 Kite and Gilead, and Kite and Gilead assume no obligation and disclaim any intent to update any such forward-looking statements.

[1] Clinicaltrials.gov. Efficacy of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma (ZUMA-7). NCT03391466. Available at: https://clinicaltrials.gov/ct2/show/NCT03391466. Accessed March 2023.

[2] European Medicines Agency. Yescarta^® (axicabtagene ciloleucel) SPC. Available at: https://www.ema.europa.eu/documents/product-information/yescarta-epar-product-information_en.pdf. Accessed March 2023.

[3] Data on file.

^[4] Leukemia & Lymphoma Society. NHL subtypes. Available at: https://www.lls.org/lymphoma/non-hodgkin-lymphoma/diagnosis/nhl-subtypes. Accessed: March 2023.

^[5] Globocan 2020. Europe fact sheet. Available at https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf Accessed: March 2023.

^[6] Sehn LH and Salles G. Diffuse Large B-Cell Lymphoma. N Engl J Med 2021;384:842-58.

^[7] Susanibar-Adaniya, S and Barta SK. 2021 Update on Diffuse large B cell lymphoma: A review of current data and potential applications on risk stratification and management. Am J Hematol. 2021 May 01; 96(5): 617–629.

^[8] Crump M, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017 Oct 19;130(16):1800-8.