Kite Submits Supplemental Biologics License Application to U.S. Food and Drug Administration for Yescarta® in Relapsed or Refractory Indolent Non-Hodgkin Lymphomas

-- If Approved, Yescarta would be the First CAR T Therapy for Patients with Relapsed or Refractory Follicular Lymphoma and Marginal Zone Lymphoma --

SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announced that it has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for Yescarta^® (axicabtagene ciloleucel) for the treatment of relapsed or refractory follicular lymphoma and marginal zone lymphoma after two or more prior lines of systemic therapy. Yescarta was previously granted Breakthrough Therapy Designation (BTD) by the FDA for these indications. If approved, Yescarta would become the first chimeric antigen receptor (CAR) T cell therapy approved for the treatment of relapsed or refractory indolent non-Hodgkin lymphoma (NHL).

The sBLA submission is supported by data from the primary analysis of the Phase 2 ZUMA-5 trial, which is being submitted for presentation at an upcoming scientific congress. Findings from an interim analysis of ZUMA-5 were recently presented during an oral session at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.

“People living with indolent NHL often experience a disease that starts out slowly but becomes more aggressive over time with each subsequent relapse,” said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. “The efficacy observed in ZUMA-5 may provide a potentially transformative treatment option for higher-risk patients with certain types of indolent NHL. We look forward to working closely with the FDA to progress this application with the goal of bringing Yescarta to patients with indolent NHL as soon as possible.”

Yescarta was the first 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, 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 cytokine release syndrome (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.

Yescarta has not been approved by any regulatory agency for the treatment of indolent non-Hodgkin lymphoma, including follicular lymphoma or marginal zone lymphoma. Its safety and efficacy have not been established in these lymphomas.

About Indolent Non-Hodgkin Lymphoma

Follicular lymphoma and marginal zone lymphoma are both forms of indolent non-Hodgkin lymphoma (NHL) in which malignant tumors slowly grow but can become more aggressive over time.

Follicular lymphoma is the most common form of indolent lymphoma and the second most common type of lymphoma globally. It accounts for approximately 22 percent of all lymphomas diagnosed worldwide. Marginal zone lymphoma is the third most common lymphoma, accounting for 8 to 12 percent of all B-cell NHLs.

Despite advances in management and substantial improvements in long-term survival, patients living with follicular lymphoma have varied outcomes. Currently, there are no standard of care treatments for relapsed and refractory follicular lymphoma after two or more lines of therapy, and there are limited options for the treatment of relapsed or refractory marginal zone lymphoma.

About ZUMA-5

ZUMA-5 is a single-arm, multicenter, open-label Phase 2 study that aims to enroll up to 160 adult patients (≥18 years old) with relapsed or refractory indolent NHL of either follicular lymphoma or marginal zone lymphoma subtypes, who received at least two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody combined with an alkylating agent. The objectives of the study are to evaluate the efficacy and safety of a single infusion of Yescarta in this patient population. The primary endpoint of the trial is objective response rate (ORR) as assessed by an independent review committee. Secondary endpoints include complete response rate, duration of response, progression-free survival, overall survival, safety and CAR T cell and cytokines levels. The study is ongoing.

About Yescarta

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

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

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 accompanying full Prescribing Information, including BOXED WARNING and Medication Guide.

About Kite

Kite, a Gilead Company, is a biopharmaceutical company based in Santa Monica, California. 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 that the FDA may not approve Yescarta for the treatment of relapsed or refractory indolent NHL in the anticipated timelines or at all, and any marketing approvals, if granted, may have significant limitations on its use. 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 June 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.comor call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. Follow Kite on social media on Twitter (@KitePharma) and LinkedIn.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200904005123/en/

Douglas Maffei, PhD, Investors (650) 522-2739

Nathan Kaiser, Media (650) 522-1853

Source: Gilead Sciences, Inc.