Mvasi

Product Profile:

Bevacizumab-awwb (Mvasi)

Drug Category: Vascular endothelial growth factor (VEGF)–directed antibody (angiogenesis inhibitor)

Target Indications: In combination with chemotherapy for non-squamous non-small cell lung cancer (NSCLC); metastatic colorectal cancer; glioblastoma; persistent, recurrent, or metastatic carcinoma of the cervix; and metastatic renal carcinoma in combination with interferon alfa

Manufactured and developed by Amgen and Allergan. Not yet marketed.

Summary: Mvasi is a biosimilar version of bevacizumab (reference product, Avastin) manufactured by Genentech (a subsidiary of Roche). It was the first anti-cancer biosimilar to be approved by the FDA.

The biosimilar was originally designated ABP-215.  A biologic license application for its approval via the 351(k) biosimilar pathway was submitted to the Food and Drug Administration (FDA) in November 2016. The FDA’s Oncology Drug Advisory Committee unanimously recommended the approval in July 2017. The FDA approved Mvasi for use in September 2017, with extrapolation to all of Avastin’s indications. Mvasi was also approved for use in the EU in January 2018.

Mvasi is not yet marketed in the US; its developers have been embroiled in patient litigation. However, Amgen had indicated its intent to commercialize Mvasi upon the expiration of what it considers the remaining valid Genentech/Roche patents (December 18, 2018).  Amgen has not disclosed when it might begin marketing of Mvasi. Some speculate a launch date of July 2019.

About the Manufacturer

Amgen, based in Thousand Oaks, California is a leading biotechnology company. Allergan based in Dublin, Ireland is a global pharmaceutical company.

The two companies formed a collaboration in December 2011 to develop and commercialize four oncology biosimilar products. In this partnership, Amgen takes the lead for developing and manufacturing the products as well as directing the marketing efforts. Mvasi was the first approved biosimilar for the two partners.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Mvasi is the first bevacizumab biosimilar to be approved by the FDA. The product has not yet entered the marketplace. Pfizer’s Zirabev was approved by the FDA on June 27, 2019, and is also not yet launched.

Company name

Product Name

Stage of Development

Bio-Thera Solutions

BAT-1706

Phase III trial for lung cancer underway, company anticipates FDA filing in 2020

Boehringer Ingelheim

BI 695502

Phase III trial for lung cancer completed in November 2018, no extended plans to develop further in US

Celltrion

CT-P16

Phase III trial has not yet begun recruiting

Centus Biotherapeutics (AstraZeneca/Fujifilm Kyowa Kirin Biologics joint venture)

FKB238

Phase III trial in progress for NSCLC

Ligand/Outlook Therapeutics (Oncobiologics)

ONS-1045

Phase III trial for cancer expected to begin in 2019

MAbxience SA/Amneal Pharmaceuticals

BEVZ 92

Phase I trial completed for patients with metastatic colorectal cancer

Pfizer

Zirabev (bevacizumab-bvzr)

Approved by FDA June 27, 2019

Samsung Bioepis

SB8

Phase III trial for lung cancer is ongoing

Introducing the 21st FDA Approval: Pfizer’s Zirabev, a Biosimilar of Avastin

(June 28, 2019) On June 28, 2019, Pfizer announced that it had received Food and Drug Administration (FDA) approval of Zirabev™ (bevacizumab-bvzr), a biosimilar version of Roche’s Avastin®.

Amgen Withdraws Membership From Biosimilars Advocacy Group

(November 21, 2018)   Amgen withdrew in September from The Biosimilars Forum, based on disagreements with the remaining eight biosimilar-manufacturing members and perhaps internal conflicts within Amgen.

Update on Amgen v. Genentech Court Battle Over Mvasi

(August 16, 2018)  Genentech and Amgen continued their court fight over technicalities as its ongoing patent litigation is adjudicated in District Court.

Part B to Part D and Other Questions: How CMS’s Plans Could Affect Biosimilars

(August 10, 2018)  Some of these tactics are a bit late to the party, as commercial insurers and health plans have been employing them for years. To the extent that an injectable treatment can be managed through the pharmacy benefit rather than the medical benefit, the drug can be easily subjected to prior authorization, step therapy, quantity limits, and other tools routinely used.

Court Sets 2020 Trial Date for Amgen v. Genentech in Patent Fight for Mvasi

(April 26, 2018) The District Court hearing the patent litigation between Amgen and Genentech on the latter’s bevacizumab patents issued set a trial date of June 1, 2020.

Fujifilm Gains Further Exposure in Biosimilar Partnerships

(April 12, 2018)  Centus Biotherapeutics Limited,is a joint venture between Astra Zeneca and Fujifilm Kyowa Kirin Biologics. Centus seems to be involved only in development of a bevacizumab biosimilar.

Amgen/Allergan Score Positive EMA Evaluation, but Launch Will Be Delayed

(November 13, 2017) Assuming EMA final approval is received, however, Amgen and Allergan’s cancer treatment agent will not be marketed any time soon. The principal European patent is not set to expire until 2022.

Amgen Receives Approval for Bevacizumab Biosimilar

(September 14, 2017) The Food and Drug Administration announced today the approval of the first biosimilar for Roche’s Avastin®. The approval of Mvasi™ (bevacizumab-awwb) represents the first biosimilar approved in the US for the direct treatment of cancer. Amgen is partnered with Allergan in the development and marketing of the new biosimilar.

FDA Advisory Committee Unanimously Recommends Approval for Avastin® and Herceptin® Biosimilars

(July 13, 2017) The Advisory Committee voted 17-0, recommending approval of the drug for all of the originator product’s nonprotected indications.

The Mechanism of Action of Bevacizumab

The Basics of Biosimilars

Clinical Trials of Mvasi

Phase 3 Clinical Trials

One phase 3 clinical trial was submitted to the FDA to support that the product showed no clinically meaningful differences between it and the reference product Avastin. Currently, there are no other clinical trials in progress for Mvasi.

Efficacy and Safety Study of ABP 215 Compared With Bevacizumab in Patients With Advanced Non-Small Cell Lung Cancer

A randomized double-blind study comparing the biosimilar bevacizumab (ABP215) and the European-approved bevacizumab (Avastin) was conducted in 642 patients with metastatic or recurrent nonsquamous non–small cell lung cancer (NSCLC) who were also receiving first-line therapy with carboplatin and paclitaxel. The study participants received ABP 215 (328 patients) or EU-licensed Avastin (314 patients) 5 mg/kg as an IV infusion every three weeks for 6 cycles in combination with the aforementioned chemotherapy for at least 4 of the 6 cycles. The primary endpoint was the overall response rate (ORR); duration of response and progression-free survival were secondary endpoints.

Clinical equivalence was considered to be achieved when the 2-sided 90% confidence interval (CI) of the risk ratio (RR) of the objective response rate between the two study groups was with the pre-specified margin of 0.67 and 1.5.

Variable

ABP 215
(N=328)

EU-Licensed Avastin
(N=314)

Overall Response Rate

39.0%

41.7%

Duration of Response

5.8 mo
95% CI: 4.9, 7.7

5.6 mo
95% CI: 5.1, 6.1

Progression-Free Survival (Median)

6.6 mo
95% CI: 6.3, 7.9

7.9 mo
95% CI: 6.6, 8.2

Safety results were analyzed for 633 study participants (324 in the biosimilar group, 309 in the EU-licensed reference bevacizumab group). Most study participants had an adverse event (95% and 94%, respectively); 43% and 44%, respectively experienced a grade ≥3 adverse event. Treatment-emergent adverse events observed in >10% of the study participants were alopecia, nausea, neutropenia, peripheral neuropathy, and hypertension. Infusion-related reactions were similar in both groups (14% for those taking the biosimilar vs. 12% taking the reference product). Binding anti-drug antibodies developed in 1.4% and 2.5% of the study participants, respectively, whereas no one tested positive for neutralizing antibodies.

The results of the clinical trial (efficacy and safety) support that there are no clinically meaningful differences between ABP 215 and EU-licensed Avastin.

Phase 1 Study Results

A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men

A randomized, single-blind, single-dose study to assess the pharmacokinetic equivalence of the biosimilar ABP 215 and bevacizumab in healthy Japanese male subjects

Additional Study Results

Important Links and Resources

Information About Biosimilars

Patient Assistance Information*

US Biosimilar Filings Status

*This agent is not yet available for patients.

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