Alymsys (bevacizumab-maly) / Amneal, Pharmaceutical Libbs, Insud Pharma, Nichi-Iko, Stada - LARVOL DELTA

Amneal Achieves Second U.S. Biosimilars Approval with ALYMSYS (bevacizumab-maly) (Businesswire) - "Amneal Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has approved the Company’s Biologics License Application (BLA) for bevacizumab-maly, a biosimilar referencing Avastin®....ALYMSYS® (bevacizumab-maly) in the U.S. is...indicated for the treatment of: Metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first or second-line treatment; Metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan...First-Line non-squamous non-small cell lung cancer...Recurrent glioblastoma in adults; Metastatic renal cell carcinoma in combination with interferon alfa; Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan; Epithelial ovarian, fallopian tube, or primary peritoneal cancer, in combination with paclitaxel."

FDA approval • Cervical Cancer • Colorectal Cancer • Fallopian Tube Cancer • Glioblastoma • Gynecologic Cancers • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Peritoneal Cancer • Renal Cell Carcinoma

A Study Comparing the Pharmacokinetic Similarity of MB02-SP, MB02-DM and US Licensed-Avastin®. (clinicaltrials.gov) - P1 | N=114 | Completed | Sponsor: mAbxience Research S.L. | Active, not recruiting ➔ Completed

Trial completion

New NHI drugs likely to benefit more than 14,000 (Taipei Times) - "Other drugs for treating cancer that are to be covered include the dabrafenib-trametinib drug combination for treating patients with braf V600E-mutant advanced non-small cell lung cancer, and obinutuzumab for treating patient with chronic lymphocytic leukemia, the agency said...They also include bevacizumab for the treatment of non-small cell lung cancer, ovarian cancer, fallopian tube cancer or peritoneal cancer; and ibrutinib for the treatment of chronic lymphocytic leukemia....The NHIA said the inclusion of the 18 types of medication into NHI coverage is expected to benefit more than 14,554 patients and that they would be available from next month at the earliest."

Reimbursement • Chronic Lymphocytic Leukemia • Fallopian Tube Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Pooled analysis of three pharmacokinetic studies comparing biosimilar MB02 and reference bevacizumab. (PubMed, Pharmacol Res Perspect) - "This pooled analysis of three comparable PK studies further supports the bioequivalence of biosimilar MB02 to EU- and US-reference bevacizumab. No clinically meaningful differences in safety or immunogenicity were observed."

Journal • PK/PD data • Retrospective data

In Silico and In Vitro Evaluation of Bevacizumab Biosimilar MB02 as an Antitumor Agent in Canine Mammary Carcinoma. (PubMed, Animals (Basel)) - "Additionally, canine VEGF-induced microvascular endothelial cell proliferation was inhibited in a concentration-dependent manner by MB02 biosimilar. These encouraging results show a high potential for MB02 as a promising therapeutic agent for the management of CMC."

Journal • Preclinical • Breast Cancer • Oncology • 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

A randomized, double-blind, single-dose study to assess bioequivalence of MB02 biosimilar after manufacturing iteration and reference bevacizumab. (PubMed, Pharmacol Res Perspect) - "No subjects showed treatment-induced neutralizing anti-drug antibodies. This study demonstrates the PK, safety, and immunogenicity similarity and bioequivalence of MB02-SP, MB02-DM, and the reference product bevacizumab."

Clinical • Journal

Results of bevacizumab biosimilar compared with RMP for the treatment of metastatic colorectal cancer. (ASCO 2017) - P1; "These study results confirm the bioequivalence of BEVZ92 and the RMP in a real and common clinical setting, and translates the high similarity demonstrated in the in vitro and in vivo characterization into the clinical outcomes such as efficacy, immunogenicity and safety profile."

Biosimilar • Colorectal Cancer

Amneal Launches First Biosimilar with ALYMSYS (bevacizumab-maly) in the United States (Businesswire) - "Amneal Pharmaceuticals...announced the commercial launch of ALYMSYS (bevacizumab-maly), a biosimilar referencing Avastin®. ALYMSYS® is a vascular endothelial growth factor inhibitor used in oncology."

Biosimilar launch • Oncology • Solid Tumor

Similarity demonstrated between isolated charge variants of MB02, a biosimilar of bevacizumab, and Avastin® following extended physicochemical and functional characterization. (PubMed, Biologicals) - "To our knowledge, this is the first comparative analytical study of individual charge variants of a bevacizumab biosimilar following a head-to head approach and the most comprehensive N-glycosylation assessment of IgG1 charge variants. Although modifications related to N- and C-terminal, N-glycans, size heterogeneity or deamidation were specifically enriched among low abundant charge variants, they did not affect binding affinity to VEGF or FcRn and in vitro potency compared with the main species or unfractionated material."

Journal

"#FDAapproves Alymsys (bevacizumab-maly), a biosimilar to Avastin (bevacizumab): https://t.co/groVEAwdDd" (@FDA_Drug_Info)

FDA event

Similarity demonstrated between isolated charge variants of MB02, a biosimilar of bevacizumab, and Avastin® following extended physicochemical and functional characterization. (PubMed, Biologicals) - "To our knowledge, this is the first comparative analytical study of individual charge variants of a bevacizumab biosimilar following a head-to head approach and the most comprehensive N-glycosylation assessment of IgG1 charge variants. Although modifications related to N- and C-terminal, N-glycans, size heterogeneity or deamidation were specifically enriched among low abundant charge variants, they did not affect binding affinity to VEGF or FcRn and in vitro potency compared with the main species or unfractionated material."

Journal

Bevacizumab biosimilar and reference bevacizumab in subjects with stage IIIB/IV non-squamous non-small cell lung cancer (STELLA): Design of a confirmatory, double-blind, randomized, controlled study. (ASCO 2019) - P3; "Subjects aged 18-80 years, with ECOG status ≤1 and histologically confirmed NSCLC not receiving curative intent surgery or systemic therapy for advanced disease are randomized (1:1) to receive: chemotherapy (paclitaxel 200 mg/m2 and carboplatin AUC6) and either MB02 or reference bevacizumab 15 mg/kg every 3 weeks for up to 6 cycles (unless disease progression or treatment intolerance). At their last meeting in September, 2018 the independent data safety monitoring board (DSMB) recommended that the study continue without change. Clinical trial information: NCT03296163"

Clinical

[VIRTUAL] Bevacizumab biosimilar (MB02) and reference bevacizumab in patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC) (STELLA study): Multiple Imputation analysis. (ASCO 2021) - P3 | "627 subjects with newly diagnosed or recurrent stage IIIb/IV NSCLC were randomized 1:1 to receive either MB02 or EU-bevacizumab plus chemotherapy (paclitaxel and carboplatin) every 3-week cycle for six cycles (week 18) followed by MB02/bevacizumab in blinded monotherapy until disease progression, treatment intolerance, death, patient withdrawal or end of study (w52)... The clinical equivalence of MB02 with EU-bevacizumab is demonstrated by the efficacy data provided through the primary endpoint and the MI sensitive analysis applied . The MI (MAR and MNAR) represent an added value that supports the biosimilarity of MB02 and EU-bevacizumab."

Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] Bevacizumab biosimilar and reference bevacizumab in subjects with stage IIIB/IV no squamous non-small cell lung cancer (NSCLC) (STELLA study): Results for the primary endpoint in a confirmatory, double-blind, randomized, controlled study. (ASCO 2020) - " Subjects were randomized 1:1 to MB02 or bevacizumab (15 mg/kg) plus chemotherapy (paclitaxel [P] 200 mg/m2 and carboplatin [C] AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18) followed by MB02/bevacizumab in blinded monotherapy until disease progression, treatment intolerance, death, patient withdrawal or end of study (Week 52). The statistical analysis executed for ORRs confirm the equivalence of MB02 and bevacizumab, supporting the clinical activity of MB02 treatment. MB02 was well tolerated with manageable AEs in patients with Stage IIIB/IV NSCLC. Research Funding: mAbxience Research SI"

Clinical • Hematological Disorders • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Cipla expands its offer in oncology with the launch of the Bevacizumab biosimilar in Spain [Google translate] (Notimerica) - "Cipla Limited...has announced that its subsidiary, Cipla Europe NV (called Cipla Europe) has launched the biosimilar Bevacizumab (Alymsys®.)...Alymsys® is a bevacizumab biosimilar (25 mg / mL concentrate for solution for infusion) indicated for the treatment of different tumors such as lung, ovary, kidney cells, breast, cervix and colorectal cancer, in combination with other drugs against cancer. Cipla will be in charge of marketing Alymsys® in Spain."

Biosimilar launch • Breast Cancer • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma

A randomized, double blind, single dose, comparative study of the pharmacokinetics, safety and immunogenicity of MB02 (bevacizumab biosimilar) and reference bevacizumab in healthy male volunteers. (PubMed, Br J Clin Pharmacol) - P1 | "This study demonstrates the PK similarity and bioequivalence of MB02 to the reference bevacizumab, whether approved from US or EU. The safety and immunogenicity profile of MB02 was shown also to be similar to the bevacizumab reference product (NCT04238663)."

Clinical • Journal • PK/PD data • Fatigue • Pain

Stada launches the biosimilar ’Oyavas’ (bevacizumab) in Spain [Google translation] (Redacción Médica) - "Stada continues to consolidate its commitment to biosimilars with the marketing in Spain of Oyavas 25 mg/ml concentrate for solution for infusion, whose active ingredient is bevacizumab....This biosimilar medicine is indicated for the treatment of different tumors such as lung, ovarian, renal cell, breast, cervical and colorectal cancer, in combination with other cancer medicines."

Biosimilar launch • Breast Cancer • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma

A randomized, single-dose, pharmacokinetic equivalence study comparing MB02 (proposed biosimilar) and reference bevacizumab in healthy Japanese male volunteers. (PubMed, Cancer Chemother Pharmacol) - P1 | "Pharmacokinetic similarity of MB02 to reference bevacizumab was evidenced in Japanese healthy subjects, with comparable safety and immunogenicity profile between treatments. This study supports the biosimilarity of MB02 to reference bevacizumab in Japanese population. ClinicalTrials.gov identifier: NCT04238650."

Clinical • Journal • PK/PD data

A Study Comparing the Pharmacokinetic Similarity of MB02-SP, MB02-DM and USlicensed Avastin®. (clinicaltrials.gov) - P1; N=114; Active, not recruiting; Sponsor: mAbxience S.A; Recruiting ➔ Active, not recruiting; Trial completion date: Feb 2021 ➔ Aug 2021; Trial primary completion date: Feb 2021 ➔ Aug 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date

"#Amneal Announces U.S. FDA Filing Acceptance of #BiologicsLicenseApplication (#BLA) for #Bevacizumab $AMRX $AMRX https://t.co/qp1BKVaV4e" (@1stOncology)

BLA

Amneal Announces U.S. FDA Filing Acceptance of Biologics License Application (BLA) for Bevacizumab (Businesswire) - "Amneal Pharmaceuticals...announced the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for Bevacizumab, pursuant to Section 351(k) pathway of the Public Health Service Act, and with a standard review goal date in the second quarter of 2022 according to the BsUFA (Biosimilar User Fee Act)."

BLA • BsUFA date • Colorectal Cancer • Oncology

Efficacy, Safety and Immunogenicity of MB02 (Bevacizumab Biosimilar) versus Reference Bevacizumab in Advanced Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study (STELLA). (PubMed, BioDrugs) - P3 | "MB02 demonstrated similar efficacy to EU-bevacizumab, in combination with carboplatin and paclitaxel, in subjects with advanced non-squamous NSCLC, with comparable safety and immunogenicity profiles."

Clinical • Journal • P3 data • Hematological Disorders • Hypertension • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

EC approval for bevacizumab biosimilar Alymsys/Oyavas (GaBI) - "The biosimilar is developed by mAbxience, a biopharmaceutical firm with offices in Spain, Argentina and Switzerland. After receiving marketing authorization from the EC, mAbxience’s bevacizumab biosimilar has launched in Germany and The Netherlands, where it is marketed by STADA, with other countries soon to follow."

Biosimilar launch • Breast Cancer • Cervical Cancer • Colorectal Cancer • Fallopian Tube Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Renal Cell Carcinoma

Zentiva Continues Its Expansion In Oncology With The Launch Of ALYMSYS (bevacizumab) In 21 Countries Across Europe (PRNewswire) - "Zentiva and mAbxience announce their collaboration for the launch of the ALYMSYS® (bevacizumab) following its European Marketing Authorisation...The EC approval is based on a comprehensive clinical and scientific package which demonstrated biosimilarity of ALYMSYS® to the originator reference product....ALYMSYS® will be marketed by Zentiva in 21 countries across Europe."

Biosimilar launch • Licensing / partnership • Oncology