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Yescarta® Shows Positive Results as a First-Line Treatment for Patients With High-Risk Large B-cell Lymphoma

GILD | December 6, 2020

-- 85 Percent of Patients Responded to a Single Infusion of Yescarta, Including 74 Percent of Patients Achieving Complete Response --

-- ZUMA-12 Results Are First to Support Potential of CAR T in Earlier Lines of Therapy --

Kite, a Gilead Company (Nasdaq: GILD), today announced results from the interim analysis of ZUMA-12, a multicenter, open-label, single-arm Phase 2 study evaluating Yescarta ® (axicabtagene ciloleucel) as first-line therapy in patients with high-risk large B-cell lymphoma (LBCL). After a single infusion of Yescarta, 85 percent of patients achieved a response (n=27 evaluable for efficacy), including 74 percent of patients with a complete response. The data were presented in an oral session during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract #405).

“Despite well-established standard treatment regimens in newly diagnosed large B-cell lymphoma, patients with high-risk disease are underserved by currently available treatment options,” said Sattva S. Neelapu, MD, Professor, Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. “Only half of these patients achieve long-term remission with standard first-line therapy, so there is a major need for therapies with potential to improve outcomes for more patients. These early results from the ZUMA-12 trial are highly encouraging for the potential of CAR T in this earlier setting in patients with high risk.”

Among evaluable patients with centrally confirmed high-risk LBCL with at least one month of follow-up (n=27), 85 percent of patients responded, including 74 percent with a complete response. With a median follow-up of 9.3 months, 70 percent of response-evaluable patients were in an ongoing response at data cut-off, per investigator assessment. Median progression-free survival, median overall survival and median duration of response were not reached after a median follow-up of 9.5 months.

Among all safety-evaluable patients who received any dose of Yescarta with at least one month of follow-up (n=32), Grade 3 or higher cytokine release syndrome (CRS) and neurologic events (NE) occurred in 9 percent and 25 percent of patients, respectively. No Grade 5 CRS or NEs occurred. There was one Grade 5 adverse event due to COVID-19.

“Yescarta has already presented four-year survival data in patients with third-line refractory LBCL and we are now excited for what these ZUMA-12 results signal for its potential in earlier lines of treatment,” said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. “As the first positive results for a CAR T as a first-line therapy, these data are a tremendous step forward as we work to bring the benefits of Yescarta to more patients with this disease.”

Kite has presented four-year survival data for Yescarta in the ZUMA-1 study of patients with refractory large B-cell lymphoma. Based on these data and other data presented at ASH, Kite believes that Yescarta could bring the hope of survival to patients with a number of other hematological malignancies.

Yescarta was the first chimeric antigen receptor (CAR) T cell therapy to be approved by the FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), and high grade B-cell lymphoma and DLBCL arising from FL. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of CRS and neurologic toxicities, and Yescarta is approved with a risk evaluation and mitigation strategy (REMS) due to these risks; see below for Important Safety Information.

About ZUMA-12

ZUMA-12 is a multicenter, open-label, single-arm Phase 2 study that aims to enroll approximately 40 adult patients (≥18 years old) with high-risk LBCL. Patients who met the following criteria for high-risk LBCL were considered eligible for the study: double- or triple-hit lymphoma by fluorescent in situ hybridization per investigator or LBCL with IPI score ≥3; and positive interim PET per Lugano Classification after two cycles of an anti-CD20 monoclonal antibody- and anthracycline-containing regimen. Patients underwent leukapheresis (≥ two weeks after prior systemic therapy) and optional non-chemotherapy bridging at investigator discretion, followed by conditioning chemotherapy.

The primary endpoint of the trial is complete response rate per the Lugano Classification. Key secondary objectives include objective response rate, duration of response, event-free survival (EFS), progression-free survival, overall survival, frequency of adverse events, and levels of CAR T cells and cytokines in blood and serum. The study is ongoing.

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.

CYTOKINE RELEASE SYNDROME (CRS) occurred in 94% of patients, with 13% ≥ Grade 3. Among patients who died after receiving Yescarta, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to Yescarta infusion. Following infusion, monitor patients for signs and symptoms of CRS at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES occurred in 87% of patients, 98% of which occurred within the first 8 weeks with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade ≥3 occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%), and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures, as well as fatal and serious cases of cerebral edema have occurred. Following Yescarta infusion, monitor patients for signs and symptoms of neurologic toxicities at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly.

REMS: Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program called the Yescarta and Tecartus REMS Program which requires that: Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Yescarta are trained about the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS: Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of Yescarta.

SERIOUS INFECTIONS: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients. Grade ≥3 infections occurred in 23% of patients; those due to an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. Grade ≥3 cytopenias not resolved by Day 30 following Yescarta infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA and B-cell aplasia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES may develop. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS: The most common (incidence ≥20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

Please see full Prescribing Information, including BOXED WARNING and Medication Guide.

About Kite

Kite, a Gilead Company, is a biopharmaceutical company based in Santa Monica, California, with commercial manufacturing operations in North America and Europe. Kite is engaged in the development of innovative cancer immunotherapies. The company is focused on chimeric antigen receptor and T cell receptor engineered cell therapies. For more information on Kite, please visit www.kitepharma.com .

About Gilead Sciences

Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California. For more information on Gilead Sciences, please visit the company’s website at www.gilead.com .

Forward-Looking Statement

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 risk of unfavorable results from the ongoing trial of Yescarta as part of first-line therapy in LBCL. There is also the possibility of unfavorable results from other ongoing and additional clinical trials involving Yescarta. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation to update any such forward-looking statements.

U.S. Prescribing Information for Yescarta, including BOXED WARNING , is available at www.kitepharma.com and www.gilead.com .

Kite, the Kite logo, Yescarta, Tecartus and GILEAD are trademarks of Gilead Sciences, Inc. or its related companies.

For more information on Kite, please visit the company’s website at www.kitepharma.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. Follow Kite on social media on Twitter ( @KitePharma ) and LinkedIn .