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Gilead and Kite Oncology Demonstrate Growing Hematology Pipeline and Strength of Leading Cell Therapy Portfolio at EHA

BusinessWire

– Eight Presentations on Yescarta® and Tecartus® Advance Kite’s Cell Therapy Leadership –

– New Data Highlight Magrolimab’s Potential to Alter the Tumor Microenvironment –

FOSTER CITY, Calif. & SANTA MONICA, Calif.–(BUSINESS WIRE)–Gilead Sciences, Inc. (Nasdaq: GILD) and Kite, a Gilead Company, will present 17 abstracts from its industry-leading cell therapy portfolio and growing blood cancer pipeline at the upcoming 2023 European Hematology Association (EHA) Annual Congress being held in Frankfurt, Germany, June 8-11, and virtually June 14-15.

Real-World Evidence and Multi-Year Follow-Up of Pivotal Studies Reinforce Confidence in CAR T

Four real-world evidence presentations include Yescarta® (axicabtagene ciloleucel) vein-to-vein time in large B-cell lymphoma (LBCL) and early outcomes in follicular lymphoma (FL). Presentations for Tecartus® (brexucabtagene autoleucel) include outcomes in relapsed/refractory (R/R) mantle cell lymphoma (MCL) and long-term results from the Phase 3 ZUMA-3 trial in R/R B-cell acute lymphoblastic leukemia (ALL). Additional data to be presented include trials-in-progress on the use of Yescarta in FL versus standard of care (ZUMA-22), as a first-line treatment in high-risk LBCL (ZUMA-23) and in the outpatient setting (ZUMA-24).

“The presentation of longer-term follow-up data from our pivotal studies and real-world evidence reinforce the potential of cell therapy across different blood cancers, lines of treatment and settings,” said Frank Neumann, MD, PhD, Senior Vice President, Global Head of Clinical Development, Kite. “We are committed to providing ongoing insights to clinicians to support the management of patients living with difficult-to-treat blood cancers who, with few treatments currently available, face a poor prognosis.”

Magrolimab Demonstrates Potential to Improve Bone Marrow Function

Gilead will highlight data showing magrolimab’s potential effect on the tumor microenvironment to improve bone marrow function in patients with acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (HR-MDS). Other data include efficacy and safety information, healthcare resource use in patients with AML and MDS, and proof-of-concept of magrolimab on calreticulin in myelofibrosis CD34-positive cells.

“Our data at EHA demonstrate the growing breadth and promise of our development program across many different blood cancers,” said Carol O’Hear, MD, Vice President, Clinical Development, Gilead Oncology. “Important results from our CAR T-cell therapies and new data for magrolimab continue to drive innovation within our pipeline and reinforce our commitment to addressing unmet needs within hematology.”

At EHA, Gilead and Kite Oncology will present the latest data for investigational and approved blood cancer therapies including (all times CEST):

Tumor Type

Abstract Title

Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes

Abstract #P699

Date: June 9

Time: 6:00p.m.–7:00p.m. CEST

Magrolimab Alters the Tumor Microenvironment to Improve Bone Marrow Functions in Patients with Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS)

Abstract #P746

Date: June 9

Time: 6:00p.m.–7:00p.m. CEST

Real-World Analysis of a Large Electronic Medical Record Database of Patients With Higher-Risk Myelodysplastic Syndromes (HR-MDS): Treatment Profiles, Clinical Effectiveness, and Key Adverse Events

Abstract #P1003

Date: June 9

Time: 6:00p.m.–7:00p.m. CEST

Ruxolitinib and Magrolimab increases Calreticulin in Myelofibrosis CD34+ Cells In Vitro: Proof of Concept for Combination Therapy

 

Abstract #PB2008

Online Publication Only

Incidence of Drug-Induced Myelosuppression and Associated Adverse Events, Quality of Life, and Medical Resource use in Myelodysplastic Syndromes and Acute Myeloid Leukemia

Abstract #PB1888

Online Publication Only

Trial in Progress: Phase 1b/2 Study of Pivekimab Sunirine (PVEK, IMGN632) in Combination with Venetoclax/Azacitidine or Magrolimab for Patients with CD123-Positive Acute Myeloid Leukemia (AML)

Abstract #PB2021

Online Publication Only

Phase 2 Study of Oral Decitabine/Cedazuridine in Combination With Magrolimab For Previously Untreated Subjects With Intermediate to Very High-risk Myelodysplastic Syndromes (MDS)

Follicular Lymphoma

Abstract #S223

Date: June 9

Time: 3:30p.m.–3:45p.m. CEST

Real-world Early Outcomes of Axicabtagene Ciloleucel for Relapsed or Refractory Follicular Lymphoma

Abstract #P1107

Date: June 9

Time: 6:00p.m.–7:00p.m. CEST

ZUMA-22: A Phase 3, Randomized Controlled Study of Axicabtagene Ciloleucel Versus Standard-of-Care Therapy in Patients with Relapsed or Refractory Follicular Lymphoma

B-Cell Lymphoma

 

Abstract #P1204

Date: June 9

Time: 6:00p.m.–7:00p.m. CEST

Axicabtagene Ciloleucel Vein-to-Vein Time in Trial or Real-World Settings vs Other CAR T-cell Therapies for Relapsed/Refractory Large B-cell Lymphoma: A Systematic Literature Review and Meta-Analysis

Abstract #PB2319

Online Publication Only

ZUMA-23: A Global Phase 3, Randomized Controlled Study of Axicabtagene Ciloleucel Versus Standard of Care as First-Line Therapy in Patients with High-Risk Large B-Cell Lymphoma

Abstract #PB2346

Online Publication Only

ZUMA-24: A Phase 2, Open-Label, Multicenter Study of Axicabtagene Ciloleucel in Patients with Relapse/Refractory Large B-Cell Lymphoma Given with Corticosteroids in the Outpatient Setting

Abstract #PB2306

Online Publication Only

Real-World First-Line Treatment and Outcomes Among Patients with High-Risk Diffuse Large B-Cell Lymphoma Treated with Standard Of Care

Abstract #P1694

Date: June 9

Time: 6:00p.m.–7:00p.m. CEST

Cost-Effectiveness of Axicabtagene Ciloleucel Vs. Tisagenlecleucel for the Treatment of Relapsed/Refractory large B-Cell Lymphoma: Updated survival results from the ZUMA-1 and Juliet Trials

Acute Lymphoblastic Leukemia

Abstract #P367

Date: June 9

Time: 6:00p.m.–7:00p.m. CEST

Long-Term Outcomes of Adults with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Treated with Brexucabtagene Autoleucel in ZUMA-3 by age, Prior Therapies and Subsequent Transplant

Mantle Cell Lymphoma

Abstract #S220

Date: June 9

Time: 2:45p.m.–3:00p.m. CEST

Real-World Outcomes of Brexucabtagene Autoleucel (brexu-cel) for Relapsed or Refractory Mantle Cell Lymphoma: A CIBMTR Subgroup Analysis by Prior Treatment

ALYCANTE (sponsored by LYSA/LYSARC)

Abstract #S233

Date: June 10

Time: 5:15p.m.–5:30p.m. CEST

Axicabtagene Ciloleucel as Second-Line Therapy for Large B-cell Lymphoma in Transplant-Ineligible Patients: Final Analysis of ALYCANTE, a Phase 2 Lysa study

Abstract #P1123

Date: June 9

Time: 6:00p.m.–7:00p.m. CEST

Early ctDNA Clearance After CAR T-cell Infusion Predicts Outcome in Patients with Large B-cell Lymphoma: Results from ALYCANTE, a Phase 2 Lysa study

Magrolimab is investigational and is not approved by the U.S. Food and Drug Administration or any other regulatory authority. Its safety and efficacy have not been established.

About Yescarta

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

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

CYTOKINE RELEASE SYNDROME (CRS)

CRS, including fatal or life-threatening reactions, occurred. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL), including ≥ Grade 3 in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 in 9%. Among patients with LBCL who died after receiving YESCARTA, 4 had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1-12 days) and the median duration was 7 days (range: 2-58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1-10 days) and the median duration was 7 days (range: 2-43 days). CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 in 8%. Among patients with iNHL who died after receiving YESCARTA, 1 patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1-20 days) and median duration was 6 days (range: 1-27 days) for patients with iNHL.

Key manifestations of CRS (≥ 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received tocilizumab and/or corticosteroids for ongoing Grade 1 events, CRS occurred in 93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients experienced a Grade 4 or 5 event. The median time to onset of CRS was 2 days (range: 1-8 days) and the median duration of CRS was 7 days (range: 2-16 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Thirty-one of the 39 patients (79%) developed CRS and were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing ≥ Grade 3 CRS. The median time to onset of CRS was 5 days (range: 1-15 days) and the median duration of CRS was 4 days (range: 1-10 days). Although there is no known mechanistic explanation, consider the risk and benefits of prophylactic corticosteroids in the context of pre-existing comorbidities for the individual patient and the potential for the risk of Grade 4 and prolonged neurologic toxicities.

Ensure that 2 doses of tocilizumab are available prior to YESCARTA 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

Neurologic toxicities (including immune effector cell-associated neurotoxicity syndrome) that were fatal or life-threatening occurred. Neurologic toxicities occurred in 78% (330/422) of all patients with NHL receiving YESCARTA, including ≥ Grade 3 in 25%. Neurologic toxicities occurred in 87% (94/108) of patients with LBCL in ZUMA-1, including ≥ Grade 3 in 31% and in 74% (124/168) of patients in ZUMA-7 including ≥ Grade 3 in 25%. The median time to onset was 4 days (range: 1-43 days) and the median duration was 17 days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (range: 1-133 days) and median duration was 15 days in patients with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including ≥ Grade 3 in 21%. The median time to onset was 6 days (range: 1-79 days) and the median duration was 16 days. Ninety-eight percent of all neurologic toxicities in patients with LBCL and 99% of all neurologic toxicities in patients with iNHL occurred within the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred within the first 7 days of infusion for 87% of affected patients with LBCL and 74% of affected patients with iNHL. The most common neurologic toxicities (≥ 10%) in all patients combined included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received corticosteroids at the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41) and 20% (8/41) had Grade 3 neurologic toxicities; no patients experienced a Grade 4 or 5 event. The median time to onset of neurologic toxicities was 6 days (range: 1-93 days) with a median duration of 8 days (range: 1-144 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Of those patients, 85% (33/39) developed neurologic toxicities, 8% (3/39) developed Grade 3, and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (range: 1-274 days) with a median duration of 12 days (range: 1-107 days). Prophylactic corticosteroids for management of CRS and neurologic toxicities may result in higher grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset and decrease the duration of CRS.

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 45% of patients with NHL. ≥ Grade 3 infections occurred in 17% of patients, including ≥ Grade 3 infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. 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 antimicrobials according to local guidelines.

Febrile neutropenia was observed in 36% of all patients with NHL 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.

In immunosuppressed patients, including those who have received YESCARTA, life-threatening and fatal opportunistic infections including disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The possibility of HHV-6 encephalitis and PML should be considered in immunosuppressed patients with neurologic events and appropriate diagnostic evaluations should be performed.

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, including YESCARTA. 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 39% of all patients with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA

B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia was reported as an adverse reaction in 14% of all patients with NHL. 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

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 non-laboratory adverse reactions (incidence ≥ 20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting.

The most common adverse reactions (incidence ≥ 20%) in patients with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

The most common non-laboratory adverse reactions (incidence ≥ 20%) in patients with iNHL in ZUMA-5 included fever, CRS, hypotension, encephalopathy, fatigue, headache, infections with pathogen unspecified, tachycardia, febrile neutropenia, musculoskeletal pain, nausea, tremor, chills, diarrhea, constipation, decreased appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness.

About Tecartus

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

Tecartus is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred following treatment with Tecartus. In ZUMA-2, CRS occurred in 91% (75/82) of patients receiving Tecartus, including ≥ Grade 3 CRS in 18% of patients. Among the patients who died after receiving Tecartus, one had a fatal CRS event. The median time to onset of CRS was three days (range: 1 to 13 days) and the median duration of CRS was ten days (range: 1 to 50 days). Among patients with CRS, the key manifestations (>10%) were similar in MCL and ALL and included fever (93%), hypotension (62%), tachycardia (59%), chills (32%), hypoxia (31%), headache (21%), fatigue (20%), and nausea (13%). Serious events associated with CRS included hypotension, fever, hypoxia, tachycardia, and dyspnea.

Ensure that a minimum of two doses of tocilizumab are available for each patient prior to infusion of Tecartus. Following infusion, monitor patients for signs and symptoms of CRS daily for at least seven days at the certified healthcare facility, and for four weeks thereafter.

Contacts

Jacquie Ross, Investors

investor_relations@gilead.com

Meaghan Smith, Gilead Media

public_affairs@gilead.com

Cressida Robson, Kite Media

cressida.robson@gilead.com

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