Zirabev (bevacizumab-bvzr) / Pfizer - LARVOL DELTA

Population Pharmacokinetic Comparability of CT-P16 Versus EU-Avastin® and US-Avastin® in Healthy Subjects and Patients with Non-Squamous Non-Small Cell Lung Cancer. (PubMed, BioDrugs) - P1, P3 | "Within a unified population pharmacokinetic framework, CT-P16 demonstrated comparable pharmacokinetics to both EU-Avastin® and US-Avastin®, with no clinically meaningful drug-product effect on clearance or central volume of distribution. Covariate effects mirrored those reported for reference bevacizumab, and simulated steady-state exposures were generally consistent with a published progression-free-survival-based exposure benchmark at the median level across covariate-defined patient subgroups. These findings extend the totality of evidence supporting CT-P16 biosimilarity and illustrate how population pharmacokinetic modelling can quantitatively inform a streamlined biosimilar assessment in the era of reduced reliance on comparative clinical efficacy trials."

Journal • PK/PD data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Are Biosimilars as Safe? A Comparative Study of Bevacizumab in Gynecologic Cancer (WAGO 2026) - "Conclusions Our study suggests real world differences in rates of hypertension, proteinuria and thromboembolic events with bevacizumab and its biosimilars MVASI and ZIRABEV. These findings support the need for ongoing evaluation of biosimilar agents as their use becomes ubiquitous."

Gynecologic Cancers • Oncology

Unveiling the effects of light exposure Bevacizumab stability in clinical settings. (PubMed, Int J Pharm) - "Here, the chemico-physical instability induced by real-life doses of light on Bevacizumab-bvzr is reported in relation to the observed target recognition, anti-angiogenic activity and in vitro immunogenicity. Although Bevacizumab is typically exposed to low levels of artificial and indoor light under clinical conditions, our findings indicate that it should be always protected from light. This is especially true during long IV administration periods, to avoid aggregate formation with potential reduction of the mAb therapeutic activity."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Comparison of biosimilar bevacizumab-bvzr to reference bevacizumab in the management of malignant glioma. (SNO 2025) - "CONCLUSIONS : Bevacizumab-bvzr demonstrated similar clinical efficacy and safety profile compared to reference bevacizumab in our institutional cohort. Concomitant treatment with antiplatelet therapy (OR 3.1447, p=0.0150) or anticoagulation (OR 4.9069, p=0.0010) were significantly associated with increased risk for adverse effects."

Brain Cancer • Glioma • High Grade Glioma • Solid Tumor • MGMT

Comparison of biosimilar bevacizumab-bvzr to reference bevacizumab in the management of malignant glioma. (WFNOS 2025) - P1/2 | "CONCLUSIONS : Bevacizumab-bvzr demonstrated similar clinical efficacy and safety profile compared to reference bevacizumab in our institutional cohort. Concomitant treatment with antiplatelet therapy (OR 3.1447, p=0.0150) or anticoagulation (OR 4.9069, p=0.0010) were significantly associated with increased risk for adverse effects."

Brain Cancer • CNS Tumor • High Grade Glioma • Oncology • Solid Tumor • MGMT

Consistent and rapid clinical benefit from systematic bevacizumab-bvzr in adult patients with HPV-associated recurrent respiratory papillomatosis (SITC 2025) - P2 | "Complete response was defined as no requirement for intervention during the 12-month treatment period. Patient 17 received 2 doses of bevacizumab-bvzr before developing a grade 3 infusion related reaction following dose 2 and was subsequently removed from protocol therapy"

Clinical • Lung Cancer • Oncology • CD8

The Adverse Effects and Use of Bevacizumab in Patients with Glioblastoma: A Systematic Review and Meta-Analysis. (PubMed, Pharmaceuticals (Basel)) - "BV is the active ingredient in the drugs Avastin®, Alymsys®, Mvasi® and ZiraBev®. Finally, the most common adverse effects were nausea, vomiting, fatigue and hypertension. While the beneficial properties of this pharmacological therapy have been observed, its adverse effect profile requires constant evaluation, as it includes vascular, blood and symptomatic adverse effects, which must be analyzed on a case-by-case basis and with great attention, especially in the case of more serious complications such as thromboembolic events."

Adverse events • Clinical • Journal • Retrospective data • Review • Brain Cancer • Cardiovascular • Fatigue • Glioblastoma • Glioma • Hypertension • Oncology • Solid Tumor

A Post-marketing Surveillance to Assess the Safety and Effectiveness of Zirabev in Domestic Patients With Various Cancer (clinicaltrials.gov) - P=N/A | N=0 | Withdrawn | Sponsor: Pfizer | N=400 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Brain Cancer • Breast Cancer • Cervical Cancer • CNS Tumor • Colorectal Cancer • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Genito-urinary Cancer • Glioblastoma • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Renal Cell Carcinoma • Solid Tumor

Cost-efficiency and expanded access modeling of conversion to biosimilar bevacizumab in metastatic colorectal and non-squamous non-small cell lung cancer in Medicare. (PubMed, J Med Econ) - "The objective of this study is to explore the cost-efficiency and budget-neutral expanded access of bevacizumab-bvzr in mCRC and mNSCLC in Medicare.Methods We developed a Medicare payer perspective simulation model of patients treated for mCRC and mNSCLC to estimate cost-savings from converting bevacizumab (originator) to bevacizumab-bvzr or alternative biosimilars such as bevacizumab-awwb, -maly, and -abcd...At 100% conversion, monthly savings from biosimilar conversion could fund up to 13,887 additional mCRC patient-months of treatment with bevacizumab-bvzr + FOLFOX, and up to 8,959 additional mNSCLC patient-months of treatment with bevacizumab-bvzr + paclitaxel + carboplatin...The biosimilar NNC from other biosimilars ranged from 60-4,564 and 55-4,422 for mCRC and NSCLC, respectively.Conclusion In the first cost-efficiency and expanded access study of biosimilar bevacizumab in mCRC and mNSCLC, we find that bevacizumab-bvzr-based regimens can result in substantial cost..."

Journal • Medicare • Reimbursement • US reimbursement • Colorectal Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Drugs for age-related macular degeneration. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Post-marketing Surveillance to Assess the Safety and Effectiveness of Zirabev in Domestic Patients With Various Cancer (clinicaltrials.gov) - P=N/A | N=400 | Not yet recruiting | Sponsor: Pfizer | Trial completion date: May 2025 ➔ Aug 2025 | Trial primary completion date: May 2025 ➔ Aug 2025

Metastases • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • Cervical Cancer • CNS Tumor • Colorectal Cancer • Fallopian Tube Cancer • Genito-urinary Cancer • Glioblastoma • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Renal Cell Carcinoma • Solid Tumor

Combination Chemotherapy, Bevacizumab, and/or Atezolizumab in Treating Patients With Deficient DNA Mismatch Repair Metastatic Colorectal Cancer, the COMMIT Study (clinicaltrials.gov) - P3; N=347; Recruiting; Sponsor: National Cancer Institute (NCI); Not yet recruiting ➔ Recruiting; N=439 ➔ 347

Clinical • Enrollment change • Enrollment open • IO biomarker • Mismatch repair • Monotherapy • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • MLH1 • MSH2 • MSH6 • MSI • PCR

Combination Chemotherapy, Bevacizumab, and/or Atezolizumab in Treating Patients With Deficient DNA Mismatch Repair Metastatic Colorectal Cancer, the COMMIT Study (clinicaltrials.gov) - P3; N=200; Recruiting; Sponsor: National Cancer Institute (NCI); N=347 ➔ 200

Clinical • Enrollment change • IO biomarker • Mismatch repair • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • MLH1 • MSH2 • MSH6 • MSI • PCR

Combination Chemotherapy, Bevacizumab, and/or Atezolizumab in Treating Patients With Deficient DNA Mismatch Repair Metastatic Colorectal Cancer, the COMMIT Study (clinicaltrials.gov) - P3; N=231; Recruiting; Sponsor: National Cancer Institute (NCI); Suspended ➔ Recruiting

Clinical • Enrollment open • IO biomarker • Mismatch repair • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • MLH1 • MSH2 • MSH6 • MSI • PCR

Combination Chemotherapy, Bevacizumab, and/or Atezolizumab in Treating Patients With Deficient DNA Mismatch Repair Metastatic Colorectal Cancer, the COMMIT Study (clinicaltrials.gov) - P3; N=200; Suspended; Sponsor: National Cancer Institute (NCI); Recruiting ➔ Suspended

Clinical • IO biomarker • Mismatch repair • Trial suspension • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • MLH1 • MSH2 • MSH6 • MSI • PCR

Cost-Efficiency Modeling of Conversion to Biosimilar Bevacizumab-bvzr in Metastatic Non-Small Cell Lung Cancer in Medicare (IASLC-WCLC 2024) - "Conclusions : In the first cost-efficiency and expanded access study of biosimilar bevacizumab in mNSCLC, we find that bevacizumab-bvzr + paclitaxel + carboplatin can result in substantial cost savings relative to originator-based first line treatment of patients with non-squamous mNSCLC in Medicare. These cost savings could be reinvested to treat a substantial number of additional patients with mNSCLC, or fund other costs of care in Medicare, on a budget-neutral basis."

Medicare • Metastases • Reimbursement • US reimbursement • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Recent Major Changes: Dosage and Administration, Preparation and Administration (FDA) - Action Date: 08/28/2024 | Biologic License Application (BLA): 761099

FDA approval • Colorectal Cancer

Cost-effectiveness analysis of bevacizumab biosimilars versus originator bevacizumab for metastatic colorectal cancer: a comparative study using real-world data. (PubMed, Value Health) - "Bevacizumab biosimilars demonstrated real-world cost-savings while providing similar survival benefit as originator bevacizumab, confirming the initial expectations of their implementation and supporting health system sustainability."

Cost effectiveness • HEOR • Journal • Metastases • Real-world • Real-world evidence • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Industry perspective on regulatory authority (RA) quality reviews of biosimilar applications - an evaluation of RA guidance and expectations for chemical, manufacturing, and controls information through in-depth query analysis. (PubMed, Expert Opin Biol Ther) - "Numbers/types of queries received following regulatory submissions (FDA/EMA, n = 7/n = 5) for seven biosimilars (PF-filgrastim [Nivestym], PF-rituximab [Ruxience®], PF-trastuzumab [Trazimera®], PF-bevacizumab [Zirabev®], PF-pegfilgrastim [Nyvepria®], PF-adalimumab [Abrilada™/Amsparity®], PF-infliximab [Ixifi]) from a single product portfolio were analyzed considering published regulatory authority (RA) guidance and in relation to sections/subsections of Module 3: Quality from the Common Technical Document regulatory dossier and topics based on keyword assignment. Topic assignments included: Control (12-27%/12-28%), Manufacturing (56-72%/34-66%), Stability (1-12%/2-24%), Biosimilarity (5-16%/5-25%), and Container Closure (0-3%/0-9%). The focus of both RAs on topics related to manufacturing and controls is valuable in understanding expectations for scientific and technical content related to gaining biosimilar approval."

Journal

Safety of marketed biosimilar monoclonal antibody cancer treatments in the US: a disproportionality analysis using the food and drug administration adverse event reporting system (FAERS) database. (PubMed, Expert Opin Drug Saf) - "Significant AE reporting signals were identified: 1) death for biological rituximab, pruritus for biosimilar rituximab-pvvr, and infusion related reaction for biological rituximab and biosimilar rituximab-pvvr (significantly higher ROR for rituximab-pvvr than biological rituximab, p < .0001); 2) death for biological bevacizumab and biosimilar bevacizumab-bvzr (significantly higher ROR for bevacizumab-bvzr than biological bevacizumab, p < .0001), hypertension, platelet count decreased (PCD), and proteinuria for biological bevacizumab and biosimilar bevacizumab-awwb (significantly higher ROR of PCD for bevacizumab-awwb than originator bevacizumab, p = .001); and 3) rash for biosimilar trastuzumab-anns. Findings call for large, longitudinal studies to examine causality of certain AEs with rituximab-pvvr and bevacizumab biosimilars."

Adverse events • Journal • Cardiovascular • Dermatology • Hypertension • Oncology • Pruritus • Renal Disease

Cost-effectiveness analysis of bevacizumab biosimilars for metastatic colorectal cancer: A comparative study using real-world data. (ASCO-QC 2023) - "Background: MVASI (Amgen) and Zirabev (Pfizer) are two of the earliest bevacizumab biosimilars approved for the first-line treatment of metastatic colorectal cancer (mCRC). Bevacizumab biosimilars demonstrated real-world cost-savings while providing similar survival benefit as originator bevacizumab, confirming the initial expectations of their implementation."

Clinical • Cost effectiveness • HEOR • Metastases • Real-world • Real-world evidence • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Post-marketing Surveillance to Assess the Safety and Effectiveness of Zirabev in Domestic Patients With Various Cancer (clinicaltrials.gov) - P=N/A | N=400 | Not yet recruiting | Sponsor: Pfizer | Trial completion date: Aug 2025 ➔ May 2025 | Trial primary completion date: Aug 2024 ➔ May 2025

Metastases • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • Cervical Cancer • CNS Tumor • Colorectal Cancer • Fallopian Tube Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Renal Cell Carcinoma • Solid Tumor

The Painful Problem of Biosimilars in the Clinic (Cancer Network) - "Co-editor-in-Chief Howard S. Hochster, MD, discusses persistent obstacles to the effective use of biosimilars in clinical practice."

Media quote

Use of Bevacizumab Originator versus Biosimilar Drugs for Oncology Indications in a Real-World Data Sample (HOPA 2023) - "This large real-world analysis showed that bevacizumab biosimilar use for on- and off-label indications increased substantially over time. Mvasi, although approved in April 2017, was not launched until July 2019, and Zirabev was unavailable until December 2019, accounting for low biosimilar use in 2019 and early 2020. Decreases in the originator drug and biosimilar drug use dropped in late 2020, which may be attributed to the COVID-19 pandemic."

Clinical • Real-world • Real-world evidence • Brain Cancer • CNS Tumor • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Glioblastoma • Infectious Disease • Novel Coronavirus Disease • Oncology • Peritoneal Cancer • Solid Tumor

Ocular Safety and Toxicokinetics of Bevacizumab-bvzr (Zirabev), a Bevacizumab Biosimilar, Administered to Cynomolgus Monkeys by Intravitreal Injection. (PubMed, J Ocul Pharmacol Ther) - "Bevacizumab-bvzr-related trace pigment or cells in vitreous humor (in 4 of 12 animals; commonly associated with IVT injection) and transient, nonadverse, mild ocular inflammation (in 1 of 12 animals) were noted upon ophthalmic examination and fully reversed during the recovery phase. Bevacizumab-bvzr was well tolerated via biweekly IVT administration in healthy monkeys, with an ocular safety profile comparable to saline or its vehicle control."

Journal • Inflammation • Ocular Inflammation • Ophthalmology