Veltuzumab

Global Pharmaceutical Research and Development Progress1.Roche's Oral Highly Selective PI3Kα Inhibitor Inavolisib Submitted for Marketing Approval in China On June 3rd, the CDE website showed that Roche's PI3Kα inhibitor Inavolisib (GDC-0077) has been submitted for marketing approval in China. It is intended for use in combination with palbociclib and fulvestrant for the treatment of adult patients with locally advanced or metastatic breast cancer who have a PIK3CA mutation, are hormone receptor-positive (HR+), and human epidermal growth factor receptor 2-negative (HER2-), and have experienced a recurrence within 12 months after adjuvant endocrine therapy or after completing such therapy. Recently, Roche also submitted a marketing application for this drug to the FDA. In December 2023, Roche presented the results of the Phase III INAVO120 trial of Inavolisib for the treatment of breast cancer at the San Antonio Breast Cancer Symposium (SABCS). This study is a randomized, double-blind, placebo-controlled clinical trial (n=325) that evaluated the efficacy and safety of Inavolisib combined with palbociclib and fulvestrant compared to placebo combined with palbociclib and fulvestrant in adult patients with PIK3CA-mutant HR+/HER2- locally advanced or metastatic breast cancer. The primary endpoint of the study was progression-free survival (PFS). The results showed a statistically and clinically significant extension in median PFS for patients in the Inavolisib group compared to the placebo group (15.0 vs. 7.3 months, HR=0.43, P<0.0001). Overall survival (OS) data are still immature, but a significant positive trend has been observed (NE vs. NE, HR=0.64, P=0.0338), and further follow-up is underway, with anticipation for the next analysis. Approximately 40% of HR+ metastatic breast cancer patients have a PIK3CA gene mutation. This mutation can lead to the alteration of the PI3Kα protein, resulting in uncontrolled tumor growth, disease progression, and resistance to endocrine therapy. Inavolisib is an oral, highly selective PI3Kα inhibitor that demonstrates greater selectivity and potency for PI3Kα compared to other isoforms (PI3Kβ/δ/γ) and can specifically trigger the degradation of mutated PI3Kα protein. 2.Agios' Oral Therapy for Thalassemia, Mitapivat, Meets Primary Endpoint in Phase III Study On June 3, Agios announced that its Phase III ENERGIZE-T study of mitapivat in adult patients with transfusion-dependent (TD) α- or β-thalassemia met its primary endpoint, significantly reducing the need for transfusions. Mitapivat is a first-in-class, oral pyruvate kinase-R (PKR) activator that activates both wild-type and mutant PKR, improving the energy supply and health of red blood cells. In February 2022, mitapivat received its first FDA approval for treating adult hemolytic anemia caused by pyruvate kinase (PK) deficiency, making it the first disease-modifying therapy for this condition, marketed under the brand name Pyrukynd. The Phase III ENERGIZE-T study included 258 patients, with 155 in the mitapivat group and 83 in the placebo group, completing the 48-week double-blind study phase. The results showed that the study achieved its primary endpoint of transfusion reduction response (TRR). TRR is defined as a reduction of ≥50% in red blood cell (RBC) transfusion units over any consecutive 12-week period by Week 48 compared to baseline, equating to a reduction of ≥2 RBC units. Mitapivat significantly reduced the transfusion burden compared to placebo, with 30.4% of patients in the mitapivat group achieving TRR, compared to only 12.6% in the placebo group (bilateral p=0.0003). 3.Arrowhead's Investigational Long-Acting Therapy Plozasiran Achieves Primary Endpoint in Phase 3 Clinical Trial June 4, Arrowhead Pharmaceuticals announced topline results from the pivotal Phase 3 clinical trial PALISADE, evaluating its investigational therapy plozasiran in patients diagnosed with familial chylomicronemia syndrome (FCS). The data indicated that plozasiran successfully met the primary endpoint of triglyceride reduction, with up to a 99% decrease observed at month 12. Plozasiran also achieved all key secondary endpoints, including a reduction in the incidence of acute pancreatitis compared to placebo. The primary endpoint of the PALISADE study was the median percentage change in triglyceride levels from baseline to month 10, adjusted for placebo. At this time point, patients receiving quarterly doses of 25 mg or 50 mg of plozasiran achieved a median triglyceride reduction of 80% and 78%, respectively, with maximum reductions reaching up to 98%. At month 12, patients on 25 mg or 50 mg of plozasiran achieved a median triglyceride reduction of 78% and 73%, respectively, with maximal reductions reaching up to 99%. In contrast, patients receiving placebo showed median triglyceride level reductions of 17% and 7% at months 10 and 12, respectively. At month 10, patients in the 25 mg and 50 mg plozasiran groups had average reductions in apolipoprotein C-III (APOC3) levels of 88% and 94%, respectively. 4.InnoCare Pharma's Anti-CD19 Monoclonal Antibody Tafasitamab to be Considered for Priority Review for Treating Hematological Cancers On June 4, the latest announcement on the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) revealed that InnoCare Pharma's application for injectable tafasitamab is to be considered for priority review. The indication is for the combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant (ASCT). Tafasitamab is a humanized monoclonal antibody targeting CD19 with an optimized Fc domain. DLBCL is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for 31% to 34% of NHL cases worldwide. According to the Chinese Society of Hematology, DLBCL accounts for 45.8% of all NHL cases in China. According to information published by InnoCare Pharma, tafasitamab is a humanized monoclonal antibody targeting CD19 with an optimized Fc domain. The unique engineered Fc domain of tafasitamab significantly enhances antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), mediating the lysis of B-cell tumors through apoptosis and immune effector mechanisms. 5.Johnson & Johnson's Bispecific Antibody Rybrevant Shows Positive Phase 3 Results in First-Line Combination Therapy On June 4, Johnson & Johnson Innovative Medicine announced new data from the Phase 3 MARIPOSA study. The analysis revealed that their bispecific antibody Rybrevant (amivantamab), in combination with the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) oral drug lazertinib, significantly improves progression-free survival (PFS) in subgroups of high-risk adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletion (ex19del) or L858R substitution mutations compared to the active comparator. Specifically, the combination of amivantamab and lazertinib demonstrated a significant reduction in the risk of disease progression or death in all high-risk subgroups when compared to the active comparator TKI drug Tagrisso (osimertinib). For patients with a history of brain metastases, PFS was 18.3 months with the amivantamab combination therapy versus 13.0 months for the active comparator group, representing a 31% reduction in the risk of disease progression or death (HR=0.69, 95% CI: 0.53-0.92; P=0.010). In patients with baseline liver metastases, PFS was 18.2 months for the amivantamab combination therapy compared to 11.0 months for the active comparator group, resulting in a 42% reduction in the risk of disease progression or death (HR=0.58, 95% CI: 0.37-0.91; P=0.017). 6.GSK Announces Impressive Data for Jemperli in First-Line Treatment of Rectal Cancer On June 4, GSK announced updated long-term data from its Phase 2 clinical trial of the PD-1 inhibitor Jemperli (dostarlimab) as a first-line therapy replacing surgery for mismatch repair deficient (dMMR) locally advanced rectal cancer. According to the press release, the trial demonstrated a 100% clinical complete response rate (cCR) in 42 patients who completed Jemperli treatment. Sustained clinical complete responses were observed in the first 24 evaluated patients over a median follow-up of 26.3 months. Detailed data were presented at this year's American Society of Clinical Oncology (ASCO) Annual Meeting. Other registration trials for Jemperli in the treatment of dMMR/microsatellite instability-high (MSI-H) rectal and colorectal cancer (CRC) are currently recruiting patients. Rectal cancer, which originates in the rectum (the final part of the large intestine), is often classified as a type of colorectal cancer. Colorectal cancer is the third most commonly diagnosed cancer worldwide. Approximately 5-10% of rectal cancers are dMMR/MSI-H, characterized by mutations that affect the proper repair of DNA during cell replication. The dMMR status is a biomarker that has been shown to predict responsiveness to immune checkpoint blockade therapies such as PD-1 antibodies. 7.Philogen and Sun Pharmaceutical Submit MAA for Nidlegy, Their First Immunocytokine Product, in Europe On June 4, Philogen and Sun Pharmaceutical jointly announced that they have submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) for daromun (trade name: Nidlegy). This submission is for the neoadjuvant treatment (i.e., pre-surgical treatment) of locally advanced, fully resectable melanoma. If approved, Nidlegy will become the first marketed immunocytokine product. The MAA is primarily based on the positive outcomes from the Phase III PIVOTAL study and a Phase II study. The PIVOTAL study is a randomized, multicenter, open-label, controlled clinical trial (n=256) that evaluated the efficacy and safety of neoadjuvant treatment (i.e., Nidlegy) followed by surgery compared to surgery alone in patients with Stage IIIB/C melanoma. The primary endpoint was the proportion of patients who achieved relapse-free survival (RFS) at one year. The results demonstrated a 41% reduction in the risk of relapse or death in the Nidlegy group (HR=0.59, p=0.005), with median RFS more than doubling (16.7 vs. 6.9 months). Distant metastasis-free survival (DMFS) was also significantly extended (HR=0.60, p=0.029). Additionally, 21% of patients in the Nidlegy group achieved pathological complete response (pCR). 8.Viking's Innovative Therapy Thyroid Hormone Receptor Beta Subtype Agonist VK2809 Achieves Primary and Secondary Endpoints On June 5, Viking Therapeutics announced positive 52-week histological data from its Phase 2b VOYAGE study of the novel liver-selective thyroid hormone receptor beta (TRβ) agonist VK2809. The study, conducted in patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH)/non-alcoholic steatohepatitis (NASH), previously demonstrated that the primary endpoint was met. Compared to placebo, patients receiving VK2809 exhibited a statistically significant reduction in liver fat content from baseline to week 12. Today’s announcement reveals that secondary endpoints were also met: 52-week liver biopsy assessments showed that up to 75% of patients treated with VK2809 achieved NASH resolution without fibrosis worsening, and up to 88% experienced significant liver fat reduction. The VOYAGE study is a randomized, double-blind, placebo-controlled, multi-center international trial designed to evaluate the efficacy, safety, and tolerability of VK2809 in patients confirmed by biopsy to have NASH and liver fibrosis. The enrolled patients include those with a liver fat content of at least 8%, as measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF), and those with F2 and F3 fibrosis stages. VK2809 is an orally administered TRβ tissue- and receptor-subtype-specific agonist with liver and beta receptor subtype selectivity. It holds substantial therapeutic potential for a range of lipid disorders. VK2809 belongs to a novel class of prodrugs, which are cleaved in vivo to release a potent thyromimetic. The selective activation of TRβ receptors in liver tissue is believed to exert significant effects on cholesterol and lipoprotein levels through various mechanisms, including the upregulation of genes involved in lipid metabolism and clearance. 9.Gilead Announces Positive Long-term Results of Investigational Small Molecule Seladelpar On June 6th, Gilead Sciences announced the two-year interim results of the ongoing ASSURE study. The analysis indicated that adult patients with moderate to severe primary biliary cholangitis (PBC) receiving treatment with their investigational drug seladelpar experienced rapid and sustained reduction in patient-reported pruritus. Subgroup analysis for subjects with compensated cirrhosis showed clinically meaningful improvements in markers of cholestasis and liver injury. The U.S. FDA has accepted the new drug application for seladelpar for the treatment of PBC patients and granted it priority review status. This includes use for the treatment of pruritus as well as for adult patients with non-cirrhotic or compensated cirrhotic PBC who have had an inadequate response to or intolerance of ursodeoxycholic acid (UDCA). The FDA is expected to announce its review decision by August 14, 2024. Additionally, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have also accepted the marketing authorization applications for seladelpar. Primary biliary cholangitis is a potentially life-threatening autoimmune liver disease. The disease results in the progressive destruction of bile ducts due to continuous immune system attacks, causing cholestasis, retention of toxic bile acids within the liver, and can progress to liver fibrosis, cirrhosis, and liver failure. 10.The first human trial results of Virion's potential "first-in-class" immunotherapy are positive On June 6th, Virion Therapeutics announced early positive immunological and safety data from the first human clinical trial of its potential "first-in-class" checkpoint-modified immunotherapy, VRON-0200. This therapy aims for the functional cure of chronic Hepatitis B virus (HBV) infection. Results demonstrated that VRON-0200 exhibited good safety and tolerability, with no reported significant adverse events and no clinically relevant abnormalities detected in laboratory tests, including liver function tests. Among the nine patients with at least 28 days of immunological follow-up, the majority (n=5) showed enhanced T-cell responses post-treatment, and several patients maintained T-cell responses above baseline levels by day 91. VRON-0200 is an intramuscularly administered therapeutic immunotherapy designed to provide a functional cure for patients with chronic HBV infection. It utilizes an adenoviral vector to express HBV antigens in antigen-presenting cells while also expressing a recombinant protein that modulates checkpoint signaling pathways. Preclinical data indicate that VRON-0200 can amplify, broaden, and enhance T-cell responses by modulating checkpoint signaling pathways, potentially including T-cells that are typically not activated during chronic HBV infection, thereby improving viral control. For more information on the progress of drug development, please follow the Synapse database. Dynamics of Global Pharmaceutical Trade Cooperation1.Akeso Biopharma and Summit Further Expand Collaboration On June 3rd, Akeso Biopharma announced the signing of a supplemental license agreement with Summit Therapeutics. This agreement expands the licensed market scope for Ivonescimab, a PD-1/VEGF bispecific antibody, under their original collaboration agreement. According to the supplemental license agreement, Akeso Biopharma will receive an upfront payment and milestone payments totaling $70 million, along with royalties on sales of Ivonescimab in the newly licensed markets. The royalty rate remains consistent with the terms of the initial agreement signed on December 5, 2022. Akeso Biopharma will continue to supply Ivonescimab injection for all licensed markets, including the newly added ones, and will earn revenue from these supplies. Furthermore, the supplemental agreement strengthens the cross-regional collaboration terms, including the sharing of clinical trial data and regulatory submission documents, to expedite Ivonescimab's regulatory approval and commercialization worldwide. Summit will gain exclusive rights for the development and commercialization of Ivonescimab in North America, South America, the Middle East, and Africa. Summit will also remain responsible for the clinical development, product registration, and commercialization in all licensed regions, as well as all associated costs. 2.Alphamab and ArriVent Collaborate to Develop New ADC Drug On June 5, Alphamab Oncology announced the signing of a research and collaboration agreement with ArriVent BioPharma, Inc. Under the terms of the agreement, Alphamab will collaborate with ArriVent to utilize Alphamab's proprietary linker-payload platform (Alphatecan) and glycosylation site-specific conjugation platform to discover and develop new Antibody-Drug Conjugates (ADCs). Alphamab will retain the rights to develop and commercialize the ADC products within Mainland China, Hong Kong Special Administrative Region, Macau Special Administrative Region, and Taiwan (collectively, Greater China). Outside of Greater China, ArriVent will hold exclusive rights to develop and commercialize the related ADC products in the oncology field and will be responsible for bearing the corresponding development expenses. According to the agreement, Alphamab is entitled to receive a one-time, non-refundable upfront payment and potential milestone payments, which include milestones for product registration, development, and sales, with total payments up to $615.5 million. Additionally, Alphamab will also be entitled to tiered royalties based on the sales of each ADC product. The ADC domain has become a front-runner for domestic innovative drugs and technology platforms entering the international market. Recently, BioNTech introduced YLL Biotech's ADC technology, with a total cooperation amount reaching up to $1.8 billion. In this collaboration, Alphamab and ArriVent's agreement amounts to $615.5 million. The commercial rights arrangements for the two cooperations are slightly different. BioNTech holds global rights while YLL Biotech reserves the option for Greater China rights. In contrast, Alphamab retains direct rights for Greater China in its deal with ArriVent. 3.BMS to Lay Off 863 Employees to Save $1.5 Billion in Expenses Starting this month, Bristol-Myers Squibb (BMS) has initiated a new round of layoffs, cutting approximately 863 positions in Lawrenceville, New Jersey. Previously, in March, BMS had already laid off 75 employees in Lawrenceville. During the announcement of its first quarter financial results in April, BMS disclosed a cost reduction plan aimed at saving approximately $1.5 billion by the end of 2025. The company estimated that around 2,200 employees would be affected by the cost-cutting measures in 2024. This round of layoffs signals the official commencement of BMS's $1.5 billion savings plan. BMS has not specified the types of positions affected by this layoff nor which facility in Lawrenceville will see the cuts. According to available information, BMS has two sites in Lawrenceville: one located on Route 206 and the other on Princeton Pike. The Route 206 facility is equipped with early discovery laboratories, offices, and support services, where scientists are dedicated to discovering and developing therapies for cancer, immunology, cardiovascular diseases, and fibrosis. The Princeton Pike location houses BMS's business teams as well as partners from the R&D, product development, and supply departments. During the Q1 earnings report, BMS pointed out that the $1.5 billion cost-cutting plan involves the restructuring of organizational management and optimizing the product pipeline. At the time, the company's Chief Financial Officer David Elkins stated that reducing R&D spending would contribute two-thirds of the savings. Chief Medical Officer Samit Hirawat also added that BMS is deciding to terminate work on about a dozen clinical projects, including the follow-up version of the immunotherapy Yervoy, as well as SIRPα and BET targeted therapies. Moving forward, the company will focus on assets and projects with higher investment returns.

At Almost Four Years of Follow-up in the Pivotal ZUMA-2 Study, Median Overall Survival was 46.4 Months, Supporting Long-Term Response in Adult Patients with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) Real-World Evidence (RWE) Shows Effectiveness in Adult R/R MCL with a Complete Response Rate of 81% and 84% for High-Risk Features (Patients with TP53 /17p Deletion) RWE Also Shows a Complete Remission/CRi Rate of 76% in Adult Patients with R/R B-Cell Precursor Acute Lymphoblastic Leukemia (B-ALL) SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announced the results of four new analyses supporting the use of Tecartus® (brexucabtagene autoleucel) in relapsed/refractory mantle cell lymphoma (R/R MCL) and relapsed/refractory adult B-cell precursor acute lymphoblastic leukemia (R/R B-ALL). These results include four-year overall survival (OS) data from the pivotal ZUMA-2 study and primary results from ZUMA-18, an expanded access study, evaluating the CAR T-cell therapy Tecartus in patients with R/R MCL that were presented orally (Abstract #106) at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition. An analysis from ZUMA-2 showing that patients who received early versus late intervention for management of cytokine release syndrome (CRS) and neurological events experienced improved safety outcomes was also presented in a poster session (Abstract #2120). In addition, real-world findings on effectiveness and safety outcomes from the Center for International Blood and Marrow Transplant Research (CIBMTR) observational database of U.S. patients who received Tecartus for R/R MCL (Abstract #107) were highlighted in an oral session; CIBMTR data from adult patients with R/R B-ALL (Abstract #1029) were also presented orally today. “The clinical results and real-world evidence presented at ASH clearly support the potential for long-term response and safety of Tecartus in aggressive blood cancers for which patients have limited treatment options,” said Frank Neumann, MD, PhD, Senior Vice President, Global Head of Clinical Development, Kite. “We are particularly encouraged that the real-world evidence demonstrates consistent outcomes for Tecartus among a broader range of patients.” Detailed Information on Tecartus Abstracts: (Abstract #106) Outcomes of Patients with Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Treated with Brexucabtagene Autoleucel (Brexu-cel) in ZUMA-2 and ZUMA-18, an Expanded Access Study At a median follow-up of 47.5 months in all 68 patients with R/R MCL who had previously received anthracycline or bendamustine-containing chemotherapy; an anti CD20 antibody; and a Bruton’s tyrosine kinase inhibitor (BTKi; ibrutinib or acalabrutinib); and were treated with Tecartus in the pivotal ZUMA-2 study, median OS was 46.4 months with 30 patients (44%) still alive at data cutoff. The median OS for patients with complete response (CR) (n=46) was 58.7 months. Efficacy and safety outcomes for 23 patients with R/R MCL enrolled in ZUMA-18, a multicenter, open-label, expanded-access study of Tecartus, were also presented. With a median follow-up of 33.5 months, the investigator-assessed objective response rate (ORR) was 87% (95% Confidence Interval [CI], 66.4-97.2); 57% had a CR (95% CI, 34.5-76.8), 30% had a partial response (95% CI, 13.2-52.9), and 9% had progressive disease (95% CI, 1.1-28.0) as their best response to Tecartus. The median OS was not reached (95% CI, 10.4-not estimable) at data cutoff with a 58% OS rate at 24 months. At data cutoff, 61% of patients were still alive. All 23 patients who received Tecartus in ZUMA-18 experienced at least one Grade ≥3 adverse event (AE); Grade ≥3 CRS and neurological events occurred in one patient (4%) and eight patients (35%), respectively. Five Grade 5 AEs occurred, one that was deemed related to Tecartus therapy (multiple organ dysfunction syndrome on Day 20) and four that were deemed unrelated to Tecartus therapy (sepsis [2, Days 123 and 219], aspiration [1, on Day 49], and encephalopathy [1, on Day 68]). “Consistent with ZUMA-2 findings, which showed a median overall survival of 46.4 months in patients with a complete response, brexu-cel demonstrated a high level of efficacy in relapsed/refractory mantle cell lymphoma patients in the ZUMA-18 expanded-access study, with less serious cytokine release syndrome,” said Andre Goy, MD, ZUMA-2 investigator and Lymphoma Division Chief, John Theurer Cancer Center, Hackensack University Medical Center. “Together, the results of these two studies provide strong support for the continued use of brexu-cel in the relapsed/refractory mantle cell lymphoma setting.” (Abstract #107) Real-world Outcomes of Brexucabtagene Autoleucel (Brexu-cel) for Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL): A CIBMTR Subgroup Analysis of High-Risk Characteristics Patients with R/R MCL and TP53 mutation/deletion or high Ki-67 proliferation index (PI) have historically had limited treatment options with dismal outcomes. In a previously presented three-year follow-up of ZUMA-2, outcomes were comparable across various high-risk subgroups, including in patients with TP53 mutation or Ki-67 PI ≥ 30% or ≥ 50%. An analysis of a CIBMTR observational database of R/R MCL patients receiving Tecartus from 84 U.S. centers was presented. With a median follow-up of 12.2 months, CR rates were high among these challenging-to-treat sub-populations: For patients with deletion of TP53/17p (n=44), CR was 84% compared to 81% in those without (n=183) For patients with Ki-67 PI ≥ 50% (n=146), CR was 83% vs 84% in those with Ki-67 PI < 50% (n=111). Safety endpoints were largely consistent among all subgroups. Prolonged neutropenia and thrombocytopenia occurred more frequently in patients with vs without deletion of TP53/17p (25% vs 13% and 28% vs 16%, respectively). Grade ≥ 3 CRS occurred more frequently in ZUMA-2-ineligible vs eligible patients (13% vs 7%). After multivariable adjustment, all effectiveness and most safety outcomes were consistent regardless of deletion of TP53/17p and Ki-67 >+50%. “These real-world findings suggest that outcomes of brexu-cel treatment, including a high complete response rate, are largely consistent, regardless of ZUMA-2 eligibility or the high-risk feature subgroups analyzed. Although patients without deletion of TP53/17p appeared to have longer overall survival than patients with, the data further demonstrate the safety and durability of response of brexu-cel for patients with relapsed/refractory mantle cell lymphoma, who typically face poor prognoses and have limited treatment options,” said Swetha Kambhampati, MD, lead investigator, City of Hope assistant professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation. (Abstract #1029) Real-world outcomes of brexucabtagene autoleucel (brexu-cel) for relapsed or refractory (R/R) adult B-cell acute lymphoblastic leukemia (B-cell ALL): Evidence from the CIBMTR registry This real-world evidence study of Tecartus in adult patients with B-ALL examined a CIBMTR registry database of 150 patients across 67 centers in the United States. The assessment found the overall complete remission or complete remission with incomplete hematological recovery (CR/CRi) rate by Day 100 post-infusion was 76%, and 70% were still in remission at 6 months post-initial response (95% CI: 55-80). For those who were not in response prior to lymphodepletion (LD), 63% of these patients converted to a CR/CRi post-infusion. The OS rate at six months was 78% (95% CI: 69-84); primary causes of death were primary disease (n=13/32, 41%) and infection (n=7/32, 22%). About one-third (31%) of responders received a subsequent allogeneic stem cell transplant (allo SCT). High response rates were observed in all patients regardless of age, prior exposure to blinatumomab, prior allo SCT, or the presence of extramedullary disease prior to LD. Grade ≥3 CRS and immune effector cell-associated neurotoxicity syndrome (ICANS, ASTCT consensus) occurred in 9% and 24% of patients, respectively. Treatment for CRS and/or ICANS consisted mainly of tocilizumab (67%) and corticosteroids (51%). Most of these AEs were resolved within three weeks of infusion (CRS, 94%; ICANS, 80%). Prolonged cytopenia and neutropenia 30 days post-infusion were experienced by 42% and 33% of patients, respectively. “It is encouraging to see that the efficacy and safety outcomes of the largest real-world evidence study of brexu-cel in B-ALL are consistent with the results of the ZUMA-3 study, with high response rates in a broad, actual patient population,” said Evandro Bezerra, MD, lead investigator, hematology specialist, Ohio State University Comprehensive Cancer Center. “These findings further build our confidence in the role of brexu-cel in treating adult patients with B-ALL, including those living with high-risk comorbidities and other factors that make treatment particularly challenging.” About ZUMA-2 ZUMA-2 is a single-arm, international multicenter (US and Europe), 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 and safety after a single infusion of KTE-X19 in this patient population. The primary endpoint for the study is objective response rate and 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, OS, incidence of AEs, 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 ZUMA-18 The U.S. expanded-access ZUMA-18 trial consists of two cohorts of 27 patients per total. The primary objectives were to provide access to Tecartus for patients with R/R MCL until it was commercially available (Cohort 1) and patients with R/R MCL whose manufactured product did not meet commercial release specifications (Cohort 2). In Cohort 1, adults (≥18 years) with R/R MCL with ≥1 prior regimen underwent leukapheresis and conditioning chemotherapy followed by a single infusion of Tecartus at a target dose of 2×106 cells/kg (or fixed dose of 2x108 anti-CD19 CAR T cells for patients who are ≥100 kg). In Cohort 2, patients received Cohort 1 treatment without leukapheresis (initial leukapheresis product used). Key endpoints were safety, ORR, and OS. About Mantle Cell Lymphoma 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 Acute Lymphoblastic Leukemia ALL is an aggressive and rare type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs, and is very challenging to treat. In adults, B-ALL is the most common form, accounting for 75% of cases. Survival rates in adults with R/R B-ALL are poor, with a median OS of less than eight months. 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 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. 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 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; the possibility that Gilead and Kite may make a strategic decision to discontinue development of programs for indications currently under evaluation and, as a result, such indications may never be successfully commercialized; the risk that physicians may not see the benefits of prescribing Tecartus; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 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. The reader is cautioned that any such forward-looking statements are not guarantees of future performance 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, Tecartus, XLP and GILEAD are trademarks of Gilead Sciences, Inc., or its related companies. For more information about Kite, please visit the company’s website at or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. Follow Kite on social media on X (@KitePharma) and LinkedIn. View source version on businesswire.com: Contacts Jacquie Ross, Investors investor_relations@gilead.com Meaghan Smith, Gilead Media msmith@gilead.com Anna Padula, Kite Media apadula@kitepharma.com Source: Gilead Sciences, Inc. View this news release online at: