On June 10, 2022 Ginkgo Bioworks (NYSE: DNA), the leading horizontal platform for cell programming, reported that management is scheduled to participate in Goldman Sachs’ 43rd Annual Global Healthcare Conference, on June 15, 2022, at 10:40 a.m. PT (Press release, Ginkgo Bioworks, JUN 10, 2022, View Source [SID1234615891]).

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Further details, a webcast link, and a replay of the presentation, if available, will be posted on the company’s investor relations website at View Source

On June 10, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that updated efficacy and safety results from the teclistamab cohort of the Phase 1b TriMM-2 study (NCT04108195) (Press release, Johnson & Johnson, JUN 10, 2022, View Source [SID1234615890]).1 Teclistamab, an investigational, off-the-shelf, T-cell redirecting bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3 on T-cells, is being studied in combination with the anti-CD38 monoclonal antibody, DARZALEX (daratumumab) subcutaneous (SC) formulation, in patients with relapsed or refractory multiple myeloma (RRMM) who have received three or more prior lines of therapy.1 Patients in the study, including a high proportion with prior anti-CD38 monoclonal antibody exposure, achieved encouraging overall response rates (ORR) with this combination treatment.1 These data will be presented at the 2022 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress as an oral presentation on Sunday, 12 June (Abstract S188).

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At a median follow-up of 8.6 months (range, 0.3-19.6), 76.5 percent (39/51) of response-evaluable patients enrolled in the study achieved a response, including 36 patients (70.6 percent) who achieved a very good partial response (VGPR) or better.1 In patients with prior anti-CD38 exposure, an ORR of 73.7 percent was achieved.1 The median time to first confirmed response was one month, and responses remained durable and deepened over time.1 At the analysis cut-off, 66.7 percent of patients who achieved a response (26/39) were alive and continuing on therapy.1

"Responders to the combination of teclistamab plus subcutaneous daratumumab included patients with prior exposure to BCMA or anti-CD38 targeted agents, which is encouraging," said Paula Rodríguez-Otero†, M.D., Ph.D., Department of Hematology, Clínica Universidad de Navarra, Pamplona, Spain and principal study investigator. "These data also suggest this steroid-sparing regimen may lead to a clinically efficacious regimen in highly refractory patients."

The open-label, multicentre, multicohort Phase 1b TriMM-2 study is investigating the safety and efficacy of teclistamab in combination with daratumumab SC for patients with RRMM.1 Enrolled patients received a median of five prior lines of therapy, 58.5 percent were triple-class refractory, 30.8 percent were penta-drug refractory, and 63.1 percent were refractory to anti-CD38 treatment.1 Eighty percent of patients were refractory to their last line of therapy.1

As of April 6, 2022, 65 patients received daratumumab SC 1,800mg at the approved schedule plus teclistamab 1.5mg/kg weekly (QW) or 3mg/kg every other week (Q2W) subcutaneously.1 Pre-medications, including steroids, were limited to the two step-up doses and the first full dose of teclistamab.1 Treatment with the combination regimen were tolerable and no unexpected or overlapping toxicities were observed.1 The most common adverse events (AEs) were cytokine release syndrome (CRS) (67.7 percent, all Grade 1 or 2); neutropenia (49.2 percent, 41.5 percent Grade 3 or 4); and anaemia (41.5 percent, 27.7 percent Grade 3 or 4).1 One patient (two percent) had Grade 1 immune effector cell–associated neurotoxicity syndrome (ICANS) which fully resolved.1 Infections were experienced by 67.7 percent of patients (27.7 percent Grade 3 or 4).1 Four patients died from AEs, all unrelated to teclistamab or daratumumab SC treatment.1

"For nearly 20 years, we have been committed to overcoming multiple myeloma and an important part of our strategy is to continue to invest and develop complementary and combinable regimens that improve outcomes for patients and their caregivers," said Edmond Chan MBChB M.D. (Res), EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. "Daratumumab has become a foundational therapy for multiple myeloma, and it is exciting to see how we can continue to grow its potential through combinations with novel treatments."

Pharmacodynamic analyses demonstrate that the combination upregulates CD38+/CD8+ T-cells and proinflammatory cytokines, suggesting the potential for complementary activity.1 Additional studies are needed to fully understand the potential clinical benefit of this biological activity.

The efficacy and pharmacodynamic profile of teclistamab in combination with daratumumab SC in patients refractory to anti-CD38 therapy suggest that higher response rates may be observed in patients with anti-CD38 naïve or sensitive disease who are enrolling in the MajesTEC-3 study (NCT05083169).1,2 The ongoing Phase 3 MajesTEC-3 study compares the efficacy of the teclistamab-daratumumab combination with daratumumab SC in combination with pomalidomide and dexamethasone (DPd) or daratumumab SC in combination with bortezomib and dexamethasone (DVd).2 Patients in the trial must have received one to three prior lines of therapy including a proteasome inhibitor (PI) and lenalidomide; patients who have received only one prior line of therapy must be refractory to lenalidomide.2 Patients who have progressed on or within 60 days of the last dose of lenalidomide given as maintenance therapy are also included.2

"These data suggest the potential of a fully immune-based regimen for patients with heavily pretreated multiple myeloma," said Yusri Elsayed, M.D., M.HSc., Ph.D., Vice President, Disease Area Leader, Hematologic Malignancies, Janssen Research & Development, LLC. "We are committed to the ongoing development of this combination and other treatments for patients who remain in need of new options."

#ENDS#

About Teclistamab
Teclistamab is an investigational, fully humanised, T-cell redirecting, IgG4 bispecific antibody targeting both BCMA (B-cell maturation antigen) and CD3, on T-cells.1 BCMA is expressed at high levels on multiple myeloma cells.3,4,5,6,7 Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce killing of tumor cells.8

Teclistamab is currently being evaluated in several monotherapy and combination studies.9,10,11,12,13 In 2020, the European Commission (EC) and the United Stated (U.S.) Food and Drug Administration (FDA) both granted teclistamab Orphan Drug Designation for the treatment of multiple myeloma. In January 2021 and June 2021, teclistamab received a PRIority MEdicines (PRIME) designation by the European Medicines Agency (EMA) and Breakthrough Therapy Designation (BTD) by the U.S. FDA, respectively. PRIME offers enhanced interaction and early dialogue to optimise drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.14 The FDA grants BTD to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition based on preliminary clinical evidence that demonstrates the drug may have substantial improvement in at least one clinically significant endpoint over available therapy.15 In December 2021, Janssen submitted a Biologics License Application (BLA) to the FDA seeking approval of teclistamab for the treatment of patients with RRMM; a marketing authorisation application (MAA) was submitted to the EMA for teclistamab approval in January 2022.

About daratumumab and daratumumab SC
Janssen is committed to exploring the potential of daratumumab for patients with multiple myeloma across the spectrum of the disease. Daratumumab has been approved in eight indications for multiple myeloma, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.16

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialise daratumumab. Since launch, daratumumab has become a foundational therapy in the treatment of multiple myeloma, having been used in the treatment of more than 274,000 patients worldwide.17 Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma. Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.18

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.16 Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death.16 Daratumumab may also have an effect on normal cells.16 Data across eight Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that daratumumab based regimens resulted in significant improvement in PFS and/or OS.19,20,21,22,23,24,25,26

For further information on daratumumab, please see the Summary of Product Characteristics at: View Source

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.27 In multiple myeloma, cancerous plasma cells change and grow out of control.27 In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,500 patients died.28 While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels or kidney failure.29

On June 10, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported that data from its hematology portfolio at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress being held June 9-12, 2022, in Vienna, Austria (Press release, BeiGene, JUN 10, 2022, View Source [SID1234615889]).

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"Our data presentations at EHA (Free EHA Whitepaper) build a more complete picture of the potential for our BTK inhibitor zanubrutinib across a number of hematologic malignancies, with positive clinical results from ROSEWOOD in follicular lymphoma, long-term efficacy and safety results from ASPEN, as well as patient-reported outcomes from ALPINE and SEQUIOA." said Lai Wang, Ph.D., Global Head of R&D at BeiGene. "We are seeing our promising early pipeline beginning to mature as a result of our deep expertise in developing treatments for hematologic malignancies, and we’re pleased to present positive proof-of-concept data from two studies with our BCL2 inhibitor, BGB-11417, at this important hematology meeting."

Highlights from the broad clinical program for zanubrutinib (BRUKINSA) presented at EHA (Free EHA Whitepaper) include:

ASPEN: Long-term safety and efficacy results from the Phase 3 ASPEN trial of zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia (WM) showed that, at a median follow up of 43 months, zanubrutinib continued to demonstrate clinically meaningful efficacy and a tolerable safety profile in patients with WM.
ROSEWOOD: The Phase 2 ROSEWOOD trial of zanubrutinib plus obinutuzumab versus (vs.) obinutuzumab monotherapy in patients with relapsed/refractory (R/R) follicular lymphoma met its primary endpoint of overall response rate (ORR) and was generally well-tolerated, with safety results consistent with previous studies of both medicines.
ALPINE: In the head-to-head ALPINE trial of zanubrutinib versus ibrutinib in patients with R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), those who received zanubrutinib monotherapy reported improvements in key health-related quality of life (HRQoL) endpoints compared with patients who received ibrutinib monotherapy.
SEQUOIA: In the SEQUOIA trial of zanubrutinib vs. bendamustine plus rituximab (BR), zanubrutinib was associated with significant improvements in HRQoL in patients with treatment-naïve (TN) CLL/SLL without del(17p), as indicated by patient reported outcome (PRO) endpoints.
The ROSEWOOD and ASPEN study findings were presented at the American Society of Cancer Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2022.

BeiGene also presented two posters from proof-of-concept studies of BGB-11417, a highly selective investigational BCL2 inhibitor in CLL, non-Hodgkin’s lymphoma and acute myeloid leukemia (AML).

Preliminary data from an ongoing Phase 1/1b dose-escalation and expansion study evaluating the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose of oral BGB-11417 as monotherapy or in combination with zanubrutinib, in patients with B-cell malignancies, showed promising efficacy potential for BGB-11417 and an improved safety profile, particularly in combination cohorts.
Preliminary data from an ongoing Phase 1b/2 global, multi-center dose escalation and expansion study evaluating BGB-11417 plus azacytidine in patients with AML demonstrated the combination to be generally well-tolerated with the majority of complete responses observed by the end of Cycle 1.
Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Patients with Relapsed or Refractory Follicular Lymphoma: Primary Analysis of the Phase 2 Randomized ROSEWOOD Trial
Abstract Number: S205

The ROSEWOOD trial met its primary endpoint, with a 68.3% ORR in the zanubrutinib plus obinutuzumab arm versus 45.8% in the obinutuzumab arm (p = 0.0017) and median follow-up of 12.5 months. Zanubrutinib plus obinutuzumab was generally well-tolerated, with safety results consistent with previous studies of both medicines.

Zanubrutinib plus obinutuzumab was associated with a deep and durable response, with a complete response (CR) rate of 37.2% compared to 19.4% for obinutuzumab alone; 18-month duration of response rate was 70.9% in the zanubrutinib plus obinutuzumab arm versus 54.6% in the obinutuzumab arm.
Time to next anti-lymphoma treatment was significantly prolonged in the zanubrutinib plus obinutuzumab arm (HR 0.37 [95% CI, 0.23, 0.60].
Median progression-free survival was 27.4 months in the zanubrutinib plus obinutuzumab arm compared to 11.2 months in the obinutuzumab arm (HR: 0.51 [95% CI, 0.32, -0.81]).
The most common adverse events in the zanubrutinib plus obinutuzumab arm were thrombocytopenia or platelet count decreased (34.3% any grade; 14% grade ≥ 3) and neutrophil count decreased or neutropenia (27.3% any grade; 22.4% grade ≥ 3); other adverse events were similar between the two arms.
Infusion-related reactions were more frequent in the obinutuzumab monotherapy arm.
ASPEN: Long-term Follow-up Results of a Phase 3 Randomized Trial of Zanubrutinib vs. Versus Ibrutinib in Patients with Waldenström Macroglobulinemia (WM)
Abstract Number: P1161

With a median follow-up of 43 months, zanubrutinib continued to demonstrate a clinically meaningful efficacy and tolerable safety profile in patients with WM.

Exploratory analyses showed a consistent trend of deeper, earlier, and more durable responses (CR+VGPR) compared with ibrutinib over time.
Median time to CR+VGPR was shorter for zanubrutinib: 6.7 months (range, 1.9-42.0) vs ibrutinib: 16.6 months (range, 2.0-49.9).
Over the follow-up period, patients receiving zanubrutinib had fewer adverse events leading to death, treatment discontinuation, and dose reduction as compared with ibrutinib.
The prevalence of atrial fibrillation, hypertension, and bleeding were lower in the zanubrutinib arm at all time intervals; neutropenia occurred early, and prevalence decreased over time for patients receiving zanubrutinib.
Health-related Quality of Life Outcomes Associated with Zanubrutinib vs Ibrutinib Monotherapy in Patients with Relapsed/Refractory (R/R) CLL/SLL: Results from The Randomized Phase 3 ALPINE Trial
Abstract Number: P663

In the Phase 3 open-label ALPINE trial, HRQoL was examined at key cycles (7 and 13; corresponding to 6 and 12 months of treatment, respectively). PRO endpoints included global health status (GHS), physical and role functions, and fatigue, pain, diarrhea, and nausea/vomiting.

Adjusted completion rates for PROs were high (>85%) in both arms at Cycles 7 and 13.
Estimated mean treatment differences and 95% CI in key PRO endpoints demonstrated treatment differences, in favor of zanubrutinib, in GHS, physical functioning, and fatigue in Cycle 7, and diarrhea in Cycle 13.
Mean change from baseline showed greater improvement with zanubrutinib compared with ibrutinib at both Cycle 7 and Cycle 13.
Patient-Reported Outcomes from a Phase 3 Randomized Study of Zanubrutinib Versus Bendamustine Plus Rituximab (BR) in Patients with Treatment-naïve (TN) CLL/SLL
Abstract Number: P662

PROs were secondary endpoints in the Phase 3, open-label,SEQUOIA trial of zanubrutinib (n=241) versus bendamustine plus BR (n=238) in adult patients with TN CLL/SLL without del(17p) and were assessed using the EORTC QLQ-C30, and EQ-5D-5L VAS. The PRO endpoints included GHS, physical and role functions, and symptoms of fatigue, pain, diarrhea, and nausea/vomiting measured at critical clinical cycles of Weeks 12 and 24.

Across all patients, adjusted completion rates for PROs were high (80%) at Weeks 12 and 24.
Patients treated with zanubrutinib experienced greater improvements in HRQoL at Weeks 12 and 24 compared with patients who received BR.
By Week 24, improvements were observed with zanubrutinib vs. BR in GHS, physical functioning, role functioning as well as greater reductions in diarrhea, fatigue, and nausea/vomiting.
Comparable improvements from baseline between zanubrutinib and BR in the health status were observed at Weeks 12 and 24, respectively.
A Phase 1 Study with the Novel B-Cell Lymphoma 2 Inhibitor BGB-11417 as Monotherapy or in Combination with Zanubrutinib in Patients with B-cell Malignancies: Preliminary Data
Abstract Number: P687

This ongoing first-in-human Phase 1/1b dose-escalation and expansion study evaluated the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose of oral BGB-11417, a highly selective investigational inhibitor of BCL2, as monotherapy (n=34) or in combination with zanubrutinib (n=44), in patients with B-cell malignancies.

Early phase 1 results suggested that BGB-11417 monotherapy and combination with zanubrutinib is generally well-tolerated in patients with CLL or NHL at the dose levels tested:

Dose escalation concluded for monotherapy patients with NHL, with 1 dose limiting toxicity (DLT) seen and no MTD reached at doses as high as 640mg; 1 DLT was seen in monotherapy patients with CLL.
Transient neutropenia was the most frequent grade ≥3 AE; risk of TLS appears limited and manageable.
Dose escalation was completed for Cohort 1A, with no MTD reached through 640mg and only 1 DLT of grade 3 febrile neutropenia was seen at 160 mg Although dose escalation has not yet been completed for the other cohorts and the follow up is limited, responses were observed at the preliminary dose levels:

A reduction in ALC was noted among all patients with CLL during ramp-up, with reduction in lymphocytes noted at dose levels as low as 1 mg. Four of six R/R CLL/SLL patients receiving BGB-11417 and zanubrutinib achieved PR-L or better across dose levels ranging from 40 – 320 mg.
Preliminary Safety and Efficacy of BGB-11417, a Potent and Selective B-Cell Lymphoma 2 (BCL2) Inhibitor, in Patients with Acute Myeloid Leukemia
Abstract Number: P590

This ongoing Phase 1b/2, global, multi-center, dose-escalation and expansion study evaluated the combination of BGB-11417 and azacitidine in patients (n=31) with acute myeloid leukemia (TN unfit for intensive chemotherapy or R/R). Preliminary results showed that the 10-day regimen of BGB-11417 in 28-day cycle plus 7-day azacytidine was generally well-tolerated and active across the three dose levels tested (40, 80, 160 mg):

58% TN and 55% R/R patients with AML met CR+CRh criteria.
Most CRs (7 of 11) were achieved by the end of cycle 1.
Five of 13 evaluable CR/CRi achieved minimal residual disease negativity.
Neutropenia was the most common grade ≥3 AE (54.8%) and was manageable with growth factor support and dose modification.
DLTs of grade 4 neutropenia/thrombocytopenia occurred in two patients; safety stopping criteria were not met.
Higher dose and different dosing scheduling are being explored.
About ASPEN

ASPEN is a randomized, open-label, multi-center Phase 3 study comparing BRUKINSA to ibrutinib in patients with relapsed or refractory (R/R) or treatment-naïve WM. The primary endpoint was proportion of patients achieving complete response or very good partial response (CR+VGPR). Patients with MYD88 mutations were assigned to cohort 1 and randomized 1:1 to receive BRUKINSA 160 mg twice daily or ibrutinib 420 mg once daily. Patients without MYD88 mutations were assigned to cohort 2 and received BRUKINSA160 mg twice daily. A total of 229 patients were enrolled in the trial, with 130 patients receiving BRUKINSA and 99 patients receiving ibrutinib.

As assessed by an independent review committee (IRC) based on the modified Sixth International Workshop on Waldenström Macroglobulinemia (IWWM-6) response criteria (Treon 2015), the combined rate of complete response (CR) and very good partial response (VGPR) in the overall intention-to-treat (ITT) population was 28% with BRUKINSA (95% CI: 20, 38), compared to 19% with ibrutinib (95% CI: 12, 28). While this difference was not statistically significant (p=0.09), BRUKINSA did achieve numerically higher VGPR rates and trends towards increased response quality.

In the ASPEN trial, BRUKINSA demonstrated a more favorable safety profile compared to ibrutinib with lower frequency of certain adverse events, including atrial fibrillation or flutter (2% vs. 15%) and major hemorrhage (6% vs. 9%). Of the 101 patients with WM treated with BRUKINSA, 4% of patients discontinued due to adverse events, and adverse events leading to dose reduction occurred in 14% of patients.

About ROSEWOOD

ROSEWOOD is a randomized, open-label, Phase 2 study comparing BRUKINSA plus obinutuzumab to obinutuzumab alone in patients with R/R FL who have received two or more lines of therapy. The primary endpoint was overall response rate (ORR) assessed by independent central review (ICR) according to Lugano classification. Select secondary endpoints include investigator-assessed ORR, ICR-reviewed and investigator-assessed duration of response (DOR) and progression-free survival (PFS), overall survival (OS), ICR- and investigator-assessed CR and complete metabolic response (CMR) rate. A total of 217 patients were enrolled in the trial, with 145 patients receiving BRUKINSA plus obinutuzumab and 72 patients receiving obinutuzumab.

About BRUKINSA (zanubrutinib)

BRUKINSA (zanubrutinib) is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is supported by a broad clinical program which includes more than 3,900 subjects in 35 trials across 28 markets. To date, BRUKINSA has received more than 20 approvals covering nearly 50 countries and regions, including the United States, China, the EU, Great Britain, Canada, Australia, and additional international markets. Currently, more than 40 additional regulatory submissions are in review around the world.

U.S. INDICATIONS and IMPORTANT SAFETY INFORMATION

INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

BRUKINSA is indicated for the treatment of adult patients with Waldenström’s macroglobulinemia (WM).
BRUKINSA is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Please see full Prescribing Information including Patient Information.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher hemorrhage events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.4% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade occurred in 35% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 27% of patients, most commonly pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (26%), thrombocytopenia (11%) and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 3.6% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 8% of patients. Other second primary malignancies included malignant solid tumors (4.0%), melanoma (1.7%) and hematologic malignancies (1.2%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter were reported in 3.2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 1.1% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose.

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse reactions
The most common adverse reactions, including laboratory abnormalities, in ≥ 30% of patients who received BRUKINSA (N = 847) included decreased neutrophil count (54%), upper respiratory tract infection (47%), decreased platelet count (41%), hemorrhage (35%), decreased lymphocyte count (31%), rash (31%) and musculoskeletal pain (30%).
Drug Interactions
CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.
CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.
Specific Populations
Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 2,900 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 16,000 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the U.S., China, the European Union, Great Britain, Canada, Australia, and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the PARP inhibitor pamiparib in China.

On June 10, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported that the China National Medical Products Administration (NMPA) has approved BeiGene’s anti-PD-1 antibody, tislelizumab, in combination with chemotherapy as a first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer (NPC) (Press release, BeiGene, JUN 10, 2022, View Source [SID1234615888]).

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"The NMPA’s approval of tislelizumab in NPC is welcoming news to these many patients with the disease."

"NPC is one of the most common head and neck cancers in China and many parts of Asia. Treatment options have been limited, with chemotherapy primarily provided for front-line care. On behalf of these patients, today’s approval of tislelizumab, a potentially differentiated checkpoint inhibitor, for patients with recurrent or metastatic NPC could provide new hope," commented Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "We look forward to bringing this important immunotherapy to the underserved patient community in China."

"With nine approved indications in China, our 3,100+ science-based commercial team is working to make tislelizumab more broadly available to those who may benefit from this important immunotherapy," commented Xiaobin Wu, Ph.D., President, Chief Operating Officer, and General Manager of China, at BeiGene. "Today’s approval is a great step for patients in China with NPC."

"In the pivotal Phase 3 RATIONALE-309 trial, comparing two arms of patients receiving either tislelizumab in combination with standard chemotherapy, or a placebo with standard chemotherapy, we observed statistical and clinically meaningful improvement in progression-free survival in the tislelizumab arm as assessed by both independent review committee and clinical investigators, and a positive trend in overall survival. These results were consistent with the updated survival data with a follow up time of 15 months, and tislelizumab was generally well tolerated," said Li Zhang, M.D., professor at the Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China and Sun Yat-sen University Cancer, and the principal investigator of the trial. "The NMPA’s approval of tislelizumab in NPC is welcoming news to these many patients with the disease."

This approval was supported by clinical results from the randomized, double-blind, Phase 3 clinical trial RATIONALE 309 (NCT03924986) to evaluate the efficacy and safety of tislelizumab combined with gemcitabine and cisplatin versus placebo combined with gemcitabine and cisplatin as a first-line treatment for patients with recurrent or metastatic NPC.

As announced in May 2021, RATIONALE 309 met the primary endpoint of PFS at the planned interim analysis. Updated efficacy analyses at a median follow-up of 15.5 months, tislelizumab in combination with chemotherapy continued to demonstrate a clinically significant progression-free survival (PFS) benefit over chemotherapy and placebo for patients with RM-NPC. Meanwhile, the tislelizumab arm continued to demonstrate a positive trend in overall survival (OS) and improvement in time to disease progression or death after next-line therapy (PFS2). The safety profile of the tislelizumab and chemotherapy combination was generally manageable and consistent with safety profiles of each treatment agent. These data were presented at an ASCO (Free ASCO Whitepaper) Virtual Plenary session in April and at the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2022.

About Nasopharyngeal Cancer (NPC)

Nasopharyngeal cancer (NPC) is a malignant, squamous cell carcinoma which arises from the epithelial cells of the nasopharynx, most commonly originating in the pharyngeal recess (the fossa of Rosenmüller).i There were an estimated 62,555 new cases of NPC in China in 2020, accounting for 46.8 percent of the worldwide incidence.ii Despite the heavy public health burden of NPC in southern China and other endemic areas, relatively little is known about the etiology and prevention of NPC.iii The major risk factors for NPC are genetic predisposition, Epstein-Barr virus (EBV) infection, and consumption of salt-preserved food.iv The median overall survival rate is about 20 months in advanced NPC;v with progressively worsening prognoses falling to a three-year survival of 7-40% reported in patients with recurrent or metastatic NPC, indicating a high medical unmet need with more effective treatment urgently needed.vi,vii,viii

About RATIONALE-309

RATIONALE-309 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial (NCT03924986) designed to evaluate the efficacy and safety of tislelizumab combined with gemcitabine and cisplatin (Arm A) versus placebo combined with gemcitabine and cisplatin (Arm B) as a first-line treatment for patients with RM-NPC.

The primary endpoint of the trial is progression-free survival (PFS) in the intent-to-treat (ITT) population as assessed by an independent review committee (IRC) per RECIST v1.1 criteria; secondary endpoints include IRC-assessed overall response rate (ORR), IRC-assessed duration of response (DoR), overall survival (OS), investigator-assessed PFS, time to second objective disease progression (PFS2), and safety.

A total of 263 patients were enrolled in the trial, with 131 and 132 randomized to Arm A and Arm B, respectively, with balanced baseline characteristics between both arms. Interim results from the trial were presented in December at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress. Those data showed that at a media follow-up time of 10 months, tislelizumab demonstrated a statistically significant improvement in terms of extending progression-free survival (PFS) as well as clinically meaningful benefit on other survival endpoints compared with chemotherapy and placebo and a generally manageable safety profile.

About Tislelizumab

Tislelizumab is an anti-programmed death receptor-1 (PD-1) inhibitor designed to help aid the body’s immune cells to detect and fight tumors. Tislelizumab, a humanized monoclonal antibody, is specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene has initiated or completed more than 20 potentially registration-enabling clinical trials in 35 countries and regions, including 17 Phase 3 trials and four pivotal Phase 2 trials.

Tislelizumab is approved by the China National Medical Products Administration (NMPA) as a treatment for nine indications, including multiple approvals in non-small cell lung cancer (NSCLC). Tislelizumab has been submitted for regulatory review as a potential treatment for unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic therapy in the U.S., and in NSCLC and second-line ESCC in Europe. In January 2021, BeiGene partnered with Novartis to accelerate the clinical development and marketing of tislelizumab in North America, Europe and Japan.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 2,900 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 16,000 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the United States, China, the EU and U.K., Canada, Australia and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, including a biologics license application (BLA) under FDA review, BeiGene and Novartis announced an option, collaboration and license agreement in December 2021 for BeiGene’s TIGIT inhibitor, ociperlimab, that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene is promoting five approved Novartis Oncology products across designated regions of China.

On June 10, 2022 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that it is presenting new long-term follow-up results and subanalyses from clinical trials of its approved therapies, as well as data on investigational medicines from its broad blood cancer portfolio, at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Congress in Vienna (Press release, Genentech, JUN 10, 2022, View Source [SID1234615887]). Data include five-year results from the Phase III CLL14 study of fixed-duration Venclexta (venetoclax) plus Gazyva (obinutuzumab) in previously untreated chronic lymphocytic leukemia (CLL); the final analysis of the Phase III GALLIUM study of Gazyva plus chemotherapy in people with previously untreated advanced-stage follicular lymphoma (FL); and subanalyses from the Phase III POLARIX study of Polivy (polatuzumab vedotin) in combination with Rituxan (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Genentech will also present data from its investigational T-cell engaging bispecific antibody development programs including mosunetuzumab and glofitamab in patients receiving later lines of therapy for non-Hodgkin’s lymphoma (NHL) and cevostamab and RG6234 in relapsed or refractory (R/R) multiple myeloma (MM).

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"With these new long-term data and other studies of fixed-duration therapies in our portfolio, we are working to lessen the treatment burdens associated with long-term cancer care."

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"Blood cancers remain challenging to treat at all stages, but by improving frontline treatment options we aim to increase the likelihood of meaningful clinical outcomes for these patients," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "With these new long-term data and other studies of fixed-duration therapies in our portfolio, we are working to lessen the treatment burdens associated with long-term cancer care."

Improving Clinical Outcomes with Effective Frontline Treatment Options

Five-Year Results of Phase III CLL14 Study of Venclexta Plus Gazyva

After a median of 65.4 months following treatment with Venclexta plus Gazyva, results confirm the combination continues to be an effective fixed-duration and chemotherapy-free option for patients with previously untreated CLL and coexisting conditions. The estimated investigator-assessed progression-free survival (PFS) rate at this follow-up was 62.6% with Venclexta plus Gazyva and 27.0% with Gazyva plus chlorambucil, and the estimated overall survival (OS) rate was 81.9% versus 77.0% (HR 0.72; 95% CI: 0.48-1.09; p=0.12). In addition, the analysis found that 72.1% of patients in the Venclexta plus Gazyva arm did not require another treatment for CLL in the five years following initial treatment (HR 0.42; 95% CI: 0.31-0.57; p<0.0001). No new safety signals were observed. The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, M.D., University of Cologne.

Final Analysis of Phase III GALLIUM Study of Gazyva

After eight years of follow-up in people with previously untreated FL, a meaningful improvement in PFS was maintained with Gazyva plus chemotherapy, confirming its role as a standard of care for first-line treatment. Seven-year investigator-assessed PFS was significantly improved with Gazyva plus chemotherapy (63.4%) compared with Rituxan plus chemotherapy (55.7%; HR 0.77; 95% CI: 0.64-0.93; p=0.006). This translated into a longer time to next anti-lymphoma treatment. At seven years, 74.1% of patients receiving Gazyva plus chemotherapy had not started new anti-lymphoma therapy compared to 65.4% receiving Rituxan plus chemotherapy (HR 0.71; 95% CI: 0.58-0.87; p=0.001). The incidence of serious adverse events was 48.9% with Gazyva plus chemotherapy and 43.4% with Rituxan plus chemotherapy.

Subgroup Analyses of Pivotal Phase III POLARIX Study

Exploratory subgroup analyses of the Phase III POLARIX study of Polivy with R-CHP compared to the current standard of care, Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in people with previously untreated DLBCL further support the potential for Polivy to transform the standard of care for people with this aggressive type of lymphoma. One of the datasets being presented is an analysis of study participants from Asia (China, Hong Kong, Japan, South Korea and Taiwan). Among this subgroup, results showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP, reducing the risk of disease progression, relapse or death by 36% (HR 0.64; 95% CI: 0.40-1.03). The safety profile was generally comparable for both regimens.

Based on the positive POLARIX results from the overall study population, the European Commission (EC) approved Polivy plus R-CHP in May 2022 for the treatment of adult patients with previously untreated DLBCL.

Providing Novel Bispecific Antibodies for Patients Receiving Later Lines of Therapy in Lymphoma and Beyond

Pivotal Data from Phase II NP30179 Expansion Study of Glofitamab

The pivotal Phase II NP30179 expansion study included patients with heavily pre-treated and highly refractory DLBCL and showed fixed-duration glofitamab, an investigational CD20xCD3 T-cell engaging bispecific antibody, induced high and durable complete response (CR) rates. After a median follow-up of 12.6 months, 39.4% of patients (n=61/155) achieved a CR (primary efficacy endpoint) and half of them (51.6%; n=80/155) achieved an overall response (the percentage of patients with a partial or CR; secondary efficacy endpoint), as assessed by an independent review committee. Cytokine release syndrome (CRS) was the most common adverse event, occurring in 63.0% of patients. These data were recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting and have been submitted for approval to the European Medicines Agency (EMA). Submissions to additional health authorities worldwide, including the U.S. Food and Drug Administration (FDA), are planned this year.

Subgroup Analysis and Mosunetuzumab Retreatment from Pivotal Phase II GO29781 study

An exploratory subgroup analysis showed mosunetuzumab could be an efficacious and tolerable option in patients aged <65 and ≥65 years who had R/R FL and had received two or more prior therapies. Patients ≥65 years old achieved a higher objective response rate (ORR) than those <65 years old (87.0% vs 77.0%, respectively). Lower rates of CRS and serious adverse events were observed in patients ≥65 years old (37%) compared to those <65 years old (52%). Additional data from the GO29781 study showed that retreatment with mosunetuzumab in patients who achieved a CR but whose disease subsequently progressed was effective and the safety of retreatment was consistent with initial treatment.

The EC recently approved mosunetuzumab for the treatment of people with R/R FL who have received at least two prior systemic therapies. The U.S. FDA granted mosunetuzumab Breakthrough Therapy Designation and Orphan Drug Designation for this same patient group.

The data being presented at EHA (Free EHA Whitepaper), as well as Phase III studies currently underway, will expand the understanding of glofitamab and mosunetuzmab and their impact in both later and earlier lines of treatment, with the aim of providing robust and durable treatment outcomes for people with different types of lymphomas.

Early Data from Novel Investigational Bispecific Antibodies in R/R MM

In line with Genentech’s commitment to improving outcomes and personalizing care for people with blood cancer, the company has expanded beyond lymphoma and leukemia, evaluating two investigational medicines in MM. This is the third most common type of blood cancer, diagnosed in more than 170,000 people around the world each year and involves plasma cells (antibody-producing cells in the bone marrow). Although advances in treatment have improved outcomes, MM remains an incurable disease characterized by multiple relapses, with an overall five-year survival rate of about 55%. Genentech is presenting data at EHA (Free EHA Whitepaper) on cevostamab, an investigational FcRH5xCD3 T-cell engaging bispecific antibody that is being evaluated as a monotherapy and in combination with other medicines to treat people with R/R MM, and on RG6234, a novel GPRC5DxCD3 T-cell engaging bispecific antibody that is being studied in a Phase I trial in people with R/R MM. While early, the clinical activity and safety profiles observed with these molecules look encouraging and support further exploration.

About Venclexta

Venclexta is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to help restore the process of apoptosis.

Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood cancers.

Venclexta Indications

Venclexta is a prescription medicine used:

to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
‒ are 75 years of age or older, or
‒ have other medical conditions that prevent the use of standard chemotherapy.
It is not known if Venclexta is safe and effective in children.

Important Safety Information

What is the most important information patients should know about Venclexta?

Venclexta can cause serious side effects, including:

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids into their vein.

The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients should tell their doctor right away if they have any symptoms of TLS during treatment with Venclexta, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Patients should drink plenty of water during treatment with Venclexta to help reduce the risk of getting TLS.

Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before the first dose on the day of the first dose of Venclexta, and each time a dose is increased.

The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects. When restarting Venclexta after stopping for 1 week or longer, the patient’s doctor may again check for the risk of TLS and change the patient’s dose.

What patients should not take Venclexta?

Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased TLS.

Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other causing serious side effects.
Patients must not start new medicines during treatment with Venclexta without first talking with their doctor.
Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:

Have kidney or liver problems.
Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium.
Have a history of high uric acid levels in the blood or gout.
Are scheduled to receive a vaccine. Patients should not receive a "live vaccine" before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient should ask their doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta.
Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away.
Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients are instructed to not breastfeed during treatment with Venclexta and for 1 week after the last dose.
What to avoid while taking Venclexta:

Patients should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while they are taking Venclexta. These products may increase the amount of Venclexta in the patient’s blood.

What are the possible side effects of Venclexta?

Venclexta can cause serious side effects, including:

Low white blood cell counts (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta and may pause dosing.
Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with Venclexta. The patient’s doctor will closely monitor and treat the patient right away if they have a fever or any signs of infection during treatment with Venclexta.
Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta.

The most common side effects of Venclexta when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell count; low platelet count; low red blood cell count; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of arms, legs, hands, and feet.

The most common side effects of Venclexta in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure.

Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility.

These are not all the possible side effects of Venclexta. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at 1-800-FDA-1088 or View Source Report side effects to Genentech at 1-888-835-2555.

Please see the Venclexta full Prescribing Information, including the Medication Guide, for additional Important Safety Information.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found only on certain types of B-cells. It is thought to work by attacking targeted cells both directly and together with the body’s immune system. Gazyva is part of a collaboration between Genentech and Biogen. Combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

Gazyva Indications

Gazyva (obinutuzumab) is a prescription medicine used:

With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.
With the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.
With chemotherapy, followed by Gazyva alone in those who responded, to treat stage II bulky, III, or IV FL in adults who have not had previous FL treatment.
Important Safety Information

The most important safety information patients should know about Gazyva

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that can become serious or life-threatening, including:

Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If the patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after, their treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes.
Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. The patient’s weakened immune system could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems.
Who should not receive Gazyva:

Patients should NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva. Patients must tell their healthcare provider if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past.

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including:

Infusion Reactions: These side effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is life-threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of infusion reactions may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort.
Hypersensitivity Reactions Including Serum Sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva.
Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness.
Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP.
Low White Blood Cell Count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections.
Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced.
The most common side effects of Gazyva in CLL were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

The safety of Gazyva was evaluated based on 392 patients with relapsed or refractory NHL, including FL (81%), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) (a disease for which Gazyva is not indicated), who did not respond to or progressed within six months of treatment with rituximab product or a rituximab product-containing regimen. In patients with follicular lymphoma, the profile of side effects that were seen were consistent with the overall population who had NHL. The most common side effects of Gazyva were infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness and urinary tract infection.

A randomized, open-label multicenter trial (GALLIUM) evaluated the safety of Gazyva as compared to rituximab product in 1,385 patients with previously untreated follicular lymphoma (86%) or marginal zone lymphoma (14%). The most common side effects of Gazyva were infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation and diarrhea.

Before receiving Gazyva, patients should talk to their doctor about:

Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines.
Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, plan to become pregnant, or are breastfeeding. Gazyva may harm their unborn baby. The patient should speak to their doctor about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to their doctor about using Gazyva if they are breastfeeding.
Patients should tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Polivy (polatuzumab vedotin-piiq)

Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

Polivy U.S. Indication

Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Important Safety Information

Possible serious side effects

Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. A patient’s doctor may stop or adjust a patient’s treatment if any serious side effects occur. Patients must contact their healthcare team if there are any signs of these side effects.

Nerve problems in arms and legs: This may happen as early as after the first dose and may worsen with every dose. If a patient already has nerve pain, Polivy may make it worse. The patient’s doctor will monitor for signs and symptoms, such as changes in sense of touch, numbness or tingling in hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to walking patterns
Infusion-related reactions: A patient may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of the infusion
Infections: Patients should contact their healthcare team if they experience a fever of 100.4°F or higher, chills, cough, or pain during urination. Also, a patient’s doctor may give medication before giving Polivy, which may prevent some infections, and monitor blood counts throughout treatment with Polivy. Treatment with Polivy can cause severe low blood cell counts
Rare and serious brain infections: A patient’s doctor will monitor the patient closely for signs and symptoms of these types of infections. Patients should contact their doctor if they experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of the skin or the white part of the eyes. Patients may be at higher risk if they already have liver problems or are taking other medication
Side effects seen most often

The most common side effects during treatment were:

Low blood cell counts (platelets, red blood cells, white blood cells)
Nerve problems in arms and legs
Tiredness or lack of energy
Diarrhea
Nausea
Fever
Decreased appetite
Infections
Polivy may not be for everyone. A patient should talk to their doctor if they are:

Pregnant or may be pregnant: Data have shown that Polivy may harm an unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for at least 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for at least 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for at least 2 months after the last dose
These may not be all the side effects. Patients should talk to their healthcare provider for more information about the benefits and risks of Polivy treatment.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the full Prescribing Information for additional Important Safety Information.

About Genentech in Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit View Source