New Kite Clinical Research and Real-World Evidence for Yescarta® Demonstrate Benefit From Earlier Lines of Treatment

Rhea-AI Summary

Gilead's Kite announced new data for Yescarta® (axicabtagene ciloleucel) in treating relapsed/refractory large B-cell lymphoma (R/R LBCL). Key findings indicate that using Yescarta as a second-line treatment improves manufacturing success rates by 2.60% compared to third-line treatments, achieving a 95.08% success rate in second-line therapies. Additionally, second-line treatments showed double the median percentage of naïve-like T-cells in patients, enhancing potential outcomes.

Preliminary results from the ZUMA-24 study suggest that outpatient administration of Yescarta is feasible, with safety data consistent with prior studies. These findings will be presented at the 2024 European Hematology Association Annual Congress.

Positive

• Second-line treatment with Yescarta shows a 95.08% first-pass manufacturing success rate, 2.60% higher than third-line treatments.
• Patients treated in the second-line setting displayed a median of approximately two times as many naïve-like T-cells compared to third-line treatments.
• Preliminary data from ZUMA-24 suggests the feasibility and safety of outpatient administration of Yescarta.

Negative

• The report mentions potential severe or life-threatening side effects, including Cytokine Release Syndrome and neurologic toxicities, which require careful monitoring.
• Yescarta is available only through a restricted REMS program due to associated risks.

Insights

Oncology Doctor

Yescarta and Tecartus represent advanced CAR T-cell therapies aimed at treating relapsed and refractory large B-cell lymphoma (R/R LBCL) and non-Hodgkin lymphoma (NHL), respectively. The new analyses indicate significant benefits of using Yescarta in second-line treatments, demonstrated by a higher first-pass manufacturing success rate and a larger population of naïve-like T-cells. This translates to a more rapid availability of the therapy, critical for patient outcomes.

The presence of more naïve-like T-cells, which are younger and more versatile immune cells, implies a better immune response, correlating with improved patient outcomes. Additionally, outpatient administration being feasible offers flexibility and potential cost savings. However, it’s important to manage the risks associated with cytokine release syndrome (CRS) and neurotoxicities, which can be severe. The findings provide a promising outlook, but the risks highlight the need for careful patient selection and monitoring.

Medical Research Analyst

The comparative analysis of real-world and clinical trial data underscores the reliability and efficiency of Yescarta’s manufacturing process, particularly in second-line treatment settings. The higher first-pass manufacturing success rate (95.08% vs 92.48%) is significant. From a logistical standpoint, the ability to reduce the time from leukapheresis to infusion is a competitive advantage, suggesting Yescarta is more dependable and timely for patients in need.

Moreover, the focus on naïve-like T-cells highlights an emerging biomarker for predicting treatment success. The ZUMA-1 and ZUMA-7 trials indicate that patients treated earlier (second-line) have substantially higher median percentages of these cells, which are indicative of a robust immune response. Investors should note the ongoing studies to validate outpatient administration, potentially expanding the market and accessibility for these therapies.

Financial Analyst

The results presented by Kite, a Gilead company, indicate a potential for increased market penetration for Yescarta if second-line treatments prove to be more effective. The improved manufacturing success rates and the possibility of outpatient administration could reduce costs and increase margins. This makes the therapy more attractive not just clinically but financially.

Additionally, considering the chronic and severe nature of R/R LBCL, the retention of patients undergoing treatment and improvements in overall survival rates could lead to sustained revenue growth. However, investors should remain cautious about the risks associated with CRS and neurotoxicities, which can affect patient uptake and regulatory scrutiny. The continuous need for monitoring and the implementation of Risk Evaluation and Mitigation Strategy (REMS) programs also entail additional operational costs.

– Analysis Shows Manufacturing of Yescarta in Second-Line Treatment of Relapsed/Refractory Large B-cell Lymphoma Can Help Reduce Time from Leukapheresis to Infusion vs. Third-Line+ Treatment –

– Data Builds on Previous Evidence on the Association Between Timely Infusion and Patient Outcomes –

– Preliminary Results Supporting Safety and Feasibility of Outpatient Administration of Yescarta and Tecartus^® to be Presented –

SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announced results from three new analyses for Yescarta^® (axicabtagene ciloleucel) in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), including both new clinical research and real-world evidence highlighting manufacturing and product characteristics of Yescarta, and outpatient administration of both Yescarta and Tecartus^® (brexucabtagene autoleucel) at the 2024 European Hematology Association (EHA) Annual Congress, June 13-16, Madrid.

Results include a comparative analysis of real-world and clinical trial data (abstract P1425), which show higher manufacturing success rate and improved T-cell performance for Yescarta in second-line versus third-line plus treatment of R/R LBCL. Rapid and efficient manufacturing of CAR T-cell therapy can help reduce the time from leukapheresis to cell therapy infusion.

“We are committed to improving survival outcomes for people living with difficult-to-treat blood cancers,” said Ibrahim Elhoussieny, Vice President, Medical Affairs, Kite. “These new data support the potential benefit of utilizing Yescarta in earlier lines of treatment, both in terms of manufacturing success and product characteristics. Additional data support the safety and feasibility of administering CAR T-cell therapy in the outpatient setting. These data contribute to the body of evidence for efficient utilization and delivery of Yescarta and Tecartus and further support our ambition for patients.”

Abstract P1425

Real-World Manufacturing Experience of Axicabtagene Ciloleucel for Patients with Relapsed or Refractory Large B-Cell Lymphoma Treated in Second Line versus Third Line of Therapy and Beyond

An analysis of 4,175 patients compared the real-world manufacturing experience and clinical trial product characteristics for patients with R/R LBCL in second-line versus third-line plus treatment. The analysis found a statistically significant higher number of patients with R/R LBCL who received Yescarta as a second-line treatment (95.08% of 1,341 patients) achieved first-pass manufacturing success rate (FP-MSR); compared with patients treated third-line and beyond (92.48% of the 2,834). This 2.60% difference suggests that 26 more lots of Yescarta are successfully manufactured per 1,000 in the first attempt for patients in second-line versus patients in third-line or beyond. The FP-MSR is defined as the ability to manufacture and disposition patient lots within specification at first attempt, critical to maintaining a timely and dependable manufacturing process. Given that higher FP-MSR lessens the need for multiple manufacturing attempts, patients receiving Yescarta in second-line could potentially experience shorter vein-to-vein times.

Results further assessed the percentage of naïve-like T-cells in apheresis among evaluable patients from ZUMA-1 (third-line) and ZUMA-7 (second-line). The analysis found the median percentage of naïve-like T-cells in patient leukapheresis was 9.28% (range, 0.20-45.07; n=126; P<.0001) for second-line, versus 4.11% (range, 0.09-56.60; n=100) for third-line plus; demonstrating patients treated in second-line setting displayed a median of approximately two times as many naïve-like T-cells versus third-line plus patients. These results indicate capturing a greater naïve-like T-cell population in the initial leukapheresis material with earlier CAR T-cell therapy intervention, which is numerically associated with improved response.

“These data suggest a notable number of patients living with relapsed/refractory large B-cell lymphoma could benefit from receiving axi-cel as second-line versus third-line treatment and beyond,” said Dr. Jason Westin, study lead and Director of Lymphoma Clinical Research Program and Section Chief of Aggressive Lymphoma research team at The University of Texas MD Anderson Cancer Center. “Patients treated in second-line have both a higher rate of success of having their cell therapy manufactured at the first attempt, as well as twice as many, naïve-like T-cells collected during leukapheresis, both of which support patients potentially having a shorter vein-to-vein time. When combining these two factors, we hope this will lead to improved patient outcomes.”

Additional Data Presented for Outpatient Administration

Kite will also present two studies which evaluate the safety and efficacy of cell therapy administration within the outpatient setting. Preliminary findings, including safety data, from the ZUMA-24 study suggest that outpatient administration of Yescarta is feasible, when administered at a qualified treatment center, at the physician’s discretion with appropriate monitoring. The REMS program for healthcare facilities that dispense and administer Yescarta is described in greater detail below.

Abstract P1159

ZUMA-24 Preliminary Analysis: A Phase 2 Study of Axicabtagene Ciloleucel in the Outpatient Setting with Prophylactic Corticosteroids in Patients with Relapsed/Refractory Large B-Cell Lymphoma

ZUMA-24 is an ongoing, single-arm, open-label, multicenter, Phase 2 study evaluating the safety and efficacy of Yescarta with prophylactic corticosteroid use in patients with R/R LBCL, after one or more prior lines of therapy, in the outpatient setting. The preliminary analysis of 30 patients who underwent outpatient dosing of Yescarta, after a median follow-up of five months, demonstrated that the safety and efficacy of Yescarta was consistent with previous clinical and real-world studies.

Abstract P1191

Updated Trends in Real-World Outpatient (OP) Administration of Axicabtagene Ciloleucel (Axi-Cel) and Brexucabtagene Autoleucel (Brexu-Cel) in Relapsed/Refractory (R/R) Non-Hodgkin Lymphoma (NHL)

A real-world outpatient study assessed trends in safety and hospitalization for patients with R/R Non-Hodgkin lymphoma (NHL) who received Yescarta and Tecartus at Mayo Clinic. Safety endpoints included CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and hospitalization rates. Analysis of safety trends reported that outpatient administration of Yescarta and Tecartus was possible without added toxicity.

About Yescarta

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

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

• Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
• 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, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
  Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.
• Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES

• 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.
• T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA.
• 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)

CRS, including fatal or life-threatening reactions, occurred following treatment with YESCARTA. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL) receiving YESCARTA, including ≥ Grade 3 (Lee grading system1) CRS in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 CRS in 9%. Among patients with LBCL who died after receiving YESCARTA, four 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 to 12 days) and the median duration of CRS was 7 days (range: 2 to 58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1 to 10 days) and the median duration was 7 days (range: 2 to 43 days).

CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 CRS in 8%. Among patients with iNHL who died after receiving YESCARTA, one patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1 to 20 days) and the median duration was 6 days (range: 1 to 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 (HLH/MAS).

The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in two 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 to 8 days) and the median duration of CRS was 7 days (range: 2 to 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 at which point the patients were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing Grade 3 or higher CRS. The median time to onset of CRS was 5 days (range: 1 to 15 days) and the median duration of CRS was 4 days (range: 1 to 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 infusion of YESCARTA. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. 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 or higher infections occurred in 17% of patients, including ≥ Grade 3 or higher 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

Patients treated with YESCARTA may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes.

Monitor life-long for secondary malignancies. In the event that a secondary malignancy 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:

• Adult patients with relapsed or refractory mantle cell lymphoma (MCL).
  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.
• Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES

• Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving Tecartus. Do not administer Tecartus to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
• Neurologic toxicities, including life-threatening reactions, occurred in patients receiving Tecartus, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Tecartus. Provide supportive care and/or corticosteroids as needed.
• T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies
• Tecartus 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), including life-threatening reactions, occurred following treatment with Tecartus. CRS occurred in 92% (72/78) of patients with ALL, including ≥ Grade 3 (Lee grading system) CRS in 26% of patients. Three patients with ALL had ongoing CRS events at the time of death. The median time to onset of CRS was five days (range: 1 to 12 days) and the median duration of CRS was eight days (range: 2 to 63 days) for patients with ALL.

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. 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 Events, including those that were fatal or life-threatening, occurred following treatment with Tecartus. Neurologic events occurred in 87% (68/78) of patients with ALL, including ≥ Grade 3 in 35% of patients. The median time to onset for neurologic events was seven days (range: 1 to 51 days) with a median duration of 15 days (range: 1 to 397 days) in patients with ALL. For patients with MCL, 54 (66%) patients experienced CRS before the onset of neurological events. Five (6%) patients did not experience CRS with neurologic events and eight patients (10%) developed neurological events after the resolution of CRS. Neurologic events resolved for 119 out of 134 (89%) patients treated with Tecartus. Nine patients (three patients with MCL and six patients with ALL) had ongoing neurologic events at the time of death. For patients with ALL, neurologic events occurred before, during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients; respectively. Three patients (4%) had neurologic events without CRS. The onset of neurologic events can be concurrent with CRS, following resolution of CRS or in the absence of CRS.

The most common neurologic events (>10%) were similar in MCL and ALL and included encephalopathy (57%), headache (37%), tremor (34%), confusional state (26%), aphasia (23%), delirium (17%), dizziness (15%), anxiety (14%), and agitation (12%). Serious events including encephalopathy, aphasia, confusional state, and seizures occurred after treatment with Tecartus.

Monitor patients daily for at least seven days for patients with MCL and at least 14 days for patients with ALL at the certified healthcare facility and for four weeks following infusion for signs and symptoms of neurologic toxicities and treat promptly.

REMS Program: Because of the risk of CRS and neurologic toxicities, Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program which requires that:

• Healthcare facilities that dispense and administer Tecartus must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of two doses of tocilizumab are available for each patient for infusion within two hours after Tecartus infusion, if needed for treatment of CRS.
• Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Tecartus are trained in the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) or residual gentamicin in Tecartus.

Severe Infections: Severe or life-threatening infections occurred in patients after Tecartus infusion. Infections (all grades) occurred in 56% (46/82) of patients with MCL and 44% (34/78) of patients with ALL. Grade 3 or higher infections, including bacterial, viral, and fungal infections, occurred in 30% of patients with ALL and MCL. Tecartus should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Tecartus infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 6% of patients with MCL and 35% of patients with ALL after Tecartus infusion and may be concurrent with CRS. The febrile neutropenia in 27 (35%) of patients with ALL includes events of “febrile neutropenia” (11 (14%)) plus the concurrent events of “fever” and “neutropenia” (16 (21%)). 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, life-threatening and fatal opportunistic infections have been reported. The possibility of rare infectious etiologies (e.g., fungal and viral infections such as HHV-6 and progressive multifocal leukoencephalopathy) should be considered in 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. 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 Tecartus infusion. In patients with MCL, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 55% (45/82) of patients and included thrombocytopenia (38%), neutropenia (37%), and anemia (17%). In patients with ALL who were responders to Tecartus treatment, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 20% (7/35) of the patients and included neutropenia (12%) and thrombocytopenia (12%); Grade 3 or higher cytopenias not resolved by Day 60 following Tecartus infusion occurred in 11% (4/35) of the patients and included neutropenia (9%) and thrombocytopenia (6%). Monitor blood counts after Tecartus infusion.

Hypogammaglobulinemia: B cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with Tecartus. Hypogammaglobulinemia was reported in 16% (13/82) of patients with MCL and 9% (7/78) of patients with ALL. Monitor immunoglobulin levels after treatment with Tecartus and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement.

The safety of immunization with live viral vaccines during or following Tecartus treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least six weeks prior to the start of lymphodepleting chemotherapy, during Tecartus treatment, and until immune recovery following treatment with Tecartus.

Secondary Malignancies may develop. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. 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 Tecartus infusion. Advise patients to refrain from driving and engaging in hazardous activities, such as operating heavy or potentially dangerous machinery, during this period.

Adverse Reactions: The most common non-laboratory adverse reactions (≥ 20%) were fever, cytokine release syndrome, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting. The most common serious adverse reactions (≥ 2%) were cytokine release syndrome, febrile neutropenia, hypotension, encephalopathy, fever, infection with pathogen unspecified, hypoxia, tachycardia, bacterial infections, respiratory failure, seizure, diarrhea, dyspnea, fungal infections, viral infections, coagulopathy, delirium, fatigue, hemophagocytic lymphohistiocytosis, musculoskeletal pain, edema, and paraparesis.

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

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 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 the ability of Gilead and Kite 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 studies, including those involving Tecartus and Yescarta; uncertainties relating to regulatory applications and related filing and approval timelines, including pending or potential applications for indications currently under evaluation; 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 March 31, 2024, 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.

Kite, the Kite logo, Yescarta, Tecartus, Gilead and the Gilead logo 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. Follow Kite on social media on X (@KitePharma) and LinkedIn.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240614729632/en/

Jacquie Ross, Investors

investor_relations@gilead.com

Meaghan Smith, Gilead Media

Public_Affairs@gilead.com

Source: Gilead Sciences, Inc.

FAQ

What is the efficacy of Yescarta in second-line treatment for R/R LBCL?

Yescarta shows a 95.08% first-pass manufacturing success rate in second-line treatments for R/R LBCL, which is 2.60% higher compared to third-line treatments.

How does the percentage of naïve-like T-cells compare in second-line versus third-line Yescarta treatments?

Patients treated in second-line settings displayed a median of approximately two times as many naïve-like T-cells compared to those treated in third-line settings.

Is outpatient administration of Yescarta feasible?

Preliminary results from the ZUMA-24 study suggest that outpatient administration of Yescarta is feasible with consistent safety data.

Are there any significant risks associated with Yescarta?

Yes, Yescarta is associated with severe or life-threatening side effects such as Cytokine Release Syndrome and neurologic toxicities, requiring careful monitoring.

What is the significance of the REMS program for Yescarta?

Yescarta is available only through a restricted REMS program due to associated risks, ensuring healthcare providers are trained in managing these risks.