Kite’s Tecartus® CAR T-cell Therapy Demonstrates 78% Complete Response Rate and 90% Overall Response Rate in Largest Real-World Evidence Analysis for Relapsed/Refractory Mantle Cell Lymphoma

-- In CIBMTR Registry Analysis, Tecartus Also Demonstrates 88% Complete Response Rate and 94% Overall Response Rate in Second-and-Third-Line Treatment --

-- Data Highlighted in Oral Presentation at ASCO --

SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announces findings from the largest real-world analysis to date of Tecartus^® (brexucabtagene autoleucel) in patients with relapsed or refractory mantle cell lymphoma (R/R MCL), which show that outcomes of Tecartus therapy had consistent high complete response (CR) and overall response rates (ORR), regardless of type of prior treatment, including: Bruton's tyrosine kinase inhibitor (BTKi), bendamustine or autologous hematopoietic cell transplant (autoHCT). Higher CR was seen when Tecartus was given as second-and-third-line compared to later lines of treatment. The data are being presented orally today at the 2023 American Society of Clinical Oncology Annual Meeting (ASCO) (Abstract #7507).

“Mantle cell lymphoma is an aggressive and rare type of lymphoma, and once patients relapse or fail to respond, it is difficult to treat, with many patients undergoing four or more lines of treatment,” said Swetha Kambhampati, MD, lead investigator, City of Hope assistant professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation. “It is encouraging to see that these real-world data reinforce brexucabtagene autoleucel’s safety and efficacy, and outcomes are consistent regardless of prior course of therapy and suggest its potential benefit when used earlier in lines of treatment for relapsed/refractory patients.”

Prospective data from 380 patients registered in the Center for International Blood and Marrow Transplant Research (CIBMTR) observational database receiving Tecartus for R/R MCL from 73 U.S. treatment centers were included in this analysis; these data from standard-of-care practice were collected for the post-authorization safety study (PASS) for Tecartus in the US, which completed enrollment in December 2022. Patients had a median of four lines of prior therapy; prior to infusion, 87% were BTKi-exposed, 56% received bendamustine, and 30% received autoHCT. Median time from leukapheresis to infusion (also referred to as vein-to-vein time) was 28 days, during which time 46% received bridging therapy.

With median follow-up of 12 months, ORR was 90%, which was similar to ZUMA-2 results, and high CR (78%) was seen in patients who received Tecartus. Additionally, at 12 months, duration of response (DOR) (since earliest CR/partial response), progression-free survival (PFS) and overall survival (OS) rates were 64%, 61% and 74% respectively. Grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) (based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria) incidence were 10% and 28% respectively.

In a multivariate analysis of patients who received Tecartus in earlier lines of therapy (1-2 vs ≥ 3 prior lines of therapy), the data showed an ORR of 94% and a CR of 88%. The multivariate analysis assessed outcomes based on prior therapy; findings show that real-world effectiveness and safety outcomes with Tecartus in patients with R/R MCL are consistent regardless of prior treatment. In BTKi-naïve patients, effectiveness (ORR 92%, CR 83%) and safety outcomes are consistent when compared with prior BTKi-treated patients. In patients with prior bendamustine use, effectiveness remained consistent and prior bendamustine use was associated with a reduced risk of grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS (odds ratio [OR] 0.50; 95% confidence interval [CI], 0.30–0.84) and increased risk of prolonged thrombocytopenia (OR 1.98; 95% CI, 1.11–3.53). Within the multivariate analysis, PFS was improved in patients with prior autoHCT compared to those without prior autoHCT (hazard ratio [HR] 0.56; 95% CI, 0.35–0.88).

“Unfortunately for patients living with mantle cell lymphoma, outcomes are poor and there are limited treatment options," said Frank Neumann, MD, PhD, SVP, Kite’s Global Head of Clinical Development. “Data from this real-world registry suggest that earlier treatment with Tecartus may confer better outcomes in these difficult-to-treat patients compared to later lines and should be evaluated further in additional studies.”

About ZUMA-2 Study

ZUMA-2 is a single-arm, multicenter, open-label Phase 2 study involving 74 enrolled/leukapheresed adult patients (≥18 years old) with MCL whose disease is refractory to or has relapsed following up to five prior lines of therapy, including anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy and the BTK inhibitors ibrutinib or acalabrutinib. The objectives of the study are to evaluate the efficacy (60 patients) and safety (68 patients) after a single infusion of KTE-X19 in this patient population. The primary endpoint for the study is objective response rate in this trial is defined as the combined rate of complete responses and partial responses as assessed by an Independent Radiology Review Committee.

Secondary endpoints include duration of response, best objective response, progression-free survival, overall survival, incidence of adverse events, incidence of anti-CD19 CAR antibodies, levels of anti-CD19 CAR T cells in blood, levels of cytokines in serum, and changes over time in the EQ-5D scale score and visual analogue scale score. The study is ongoing.

About KT-US-472-5655 PASS

For a period of 15 years post-approval, the U.S. Food and Drug Administration (FDA) and other National Health Authorities require a mechanism to follow CAR T-cell therapy patients to assess safety and efficacy outcomes. The approach for this requirement for Tecartus was the development of a prospective, non-interventional cohort study.

KT-US-472-5655 is a PASS reviewed and approved by the FDA and by the National Marrow Donor Program (NMDP) central Institutional Review Board and administered by the Cellular Immunotherapy Data Resource infrastructure managed by the CIBMTR.

The primary objective of the study is to evaluate the development of subsequent neoplasms after administration of Tecartus for treatment of R/R MCL and R/R adult ALL. Secondary objectives include evaluation of OS, causes of death, relapse or progression of the primary disease, DOR, minimal residual disease (MRD) (for ALL only), subsequent allogeneic hematopoietic cell transplantation (for ALL only), incidence and severity of cytokine release syndrome, neurological events, serious infections, prolonged cytopenia and hypogammaglobulinemia, causes of death, and pregnancy outcomes.

The accrual goal for the PASS study was 500 patients with R/R MCL, which was completed in December 2022. Enrollment for R/R ALL is ongoing.

About MCL

MCL is a rare form of non-Hodgkin lymphoma (NHL) that arises from cells originating in the “mantle zone” of the lymph node and predominantly affects men over the age of 60. Approximately 33,000 people worldwide are diagnosed with MCL each year. MCL is highly aggressive following relapse, with many patients’ disease progressing following therapy.

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 and NEUROLOGIC TOXICITIES

• 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.
• 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. 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 CIBMTR

The Center for International Blood and Marrow Transplant Research is a nonprofit research collaboration between the NMDP/Be The Match, in Minneapolis, and the Medical College of Wisconsin, in Milwaukee. CIBMTR collaborates with the global scientific community to increase survival and enrich quality of life for patients. CIBMTR facilitates critical observational and interventional research through scientific and statistical expertise, a large network of centers, and a unique database of long-term clinical data for more than 635,000 people who have received hematopoietic cell transplantation and other cellular therapies. Learn more at cibmtr.org.

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 supply and commercial product manufacturing. For more information on Kite, please visit www.kitepharma.com. Follow Kite on social media on Twitter (@KitePharma) and LinkedIn.

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.

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 Tecartus; the risk that physicians and patients may not see the potential benefits of Tecartus for the treatment of adult patients with relapsed or refractory MCL; 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, 2023, 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 are 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.

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

Kite, the Kite logo, 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. Follow Kite on social media on Twitter (@KitePharma) and LinkedIn.

View source version on businesswire.com: https://www.businesswire.com/news/home/20230604005049/en/

Jacquie Ross, Investors

investor_relations@gilead.com

Anna Padula, Media

apadula@kitepharma.com

Source: Gilead Sciences, Inc.