Zirabev

Product Profile:

Bevacizumab-bvzr (Zirabev)

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 Pfizer. Not yet marketed.

Summary: Zirabev is a biosimilar version of bevacizumab (reference product, Avastin) manufactured by Genentech (a subsidiary of Roche). It was approved on June 28, 2019 and was the second bevacizumab biosimilar approved by the FDA (Mvasi was approved in September 2017).

The biosimilar was originally designated PF-06439535.  A biologic license application for its approval via the 351(k) biosimilar pathway was submitted to the Food and Drug Administration (FDA) in August 2018. The FDA approved Zirabev with extrapolation to all of Avastin’s indications, except for ovarian cancer.

Zirabev is not yet marketed in the US, whereas Mvasi is. Since Amgen began to market Mvasi in July 2019, speculation is that Pfizer will follow suit shortly.

About the Manufacturer

Pfizer entered the biosimilar market through two avenues: (1) its acquisition of Hospira and (2) its own internal pipeline development. Pfizer was established in 1849, and it is headquartered in New York City. It has a considerable portfolio of biosimilar products approved by the FDA and in various stages of filing. In addition to Zirabev, its approved biosimilars include Inflectra, the first biosimilar version of Remicade; Ixifi, another version of Remicade that will be sold overseas only; Trazimera, a biosimilar trastuzumab; Retacrit, a biosimilar epoetin that was approved in May 2018; Ruxience, a biosimilar rituximab that was approved in July 2018; and Nevistym, a biosimilar version of filgrastim that is also marketed. Pfizer’s biosimilar pipeline consists of a biosimilar adalimumab in phase 3 trials; and biosimilar pegfilgrastim in phase 1 development.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Mvasi is the first bevacizumab biosimilar to be approved by the FDA. The product entered the marketplace in July 2019. Pfizer’s Zirabev is 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

 

Multiple Sources Announce Pfizer’s Intended Launch of Bevacizumab Biosimilar December 31, 2019

(October 1, 2019) After coming to a settlement agreement (which may have been prodded by Amgen’s launch of Mvasi® in July), Pfizer can launch Zirabev® at the end of this year.

Amgen Launches Mvasi After Court Rules Against Genentech

(July 19, 2019) The partnership of Amgen and Allergan made a huge splash in the biosimilar market by announcing the simultaneous US launches of the first two biosimilars of anticancer monoclonal antibodies. The agents Kanjinta® (trastuzumab-anns) and Mvasi® (bevacizumab-awwb) were officially made available July 18.

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 Zirabev.

PF-06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin®), Both Plus Paclitaxel and Carboplatin, as First-Line Treatment for Advanced Non-Squamous Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Study.

This randomized double-blind study compared the efficacy and safety of PF-06439535 plus paclitaxel and carboplatin with that of EU-sourced Avastin in combination with paclitaxel and carboplatin in patients receiving first-line treatment of advanced non-squamous NSCLC.

Study participants were administered either treatment on day 1 of each 21-day cycle for four to six cycles. At that end of this study phase, patients were given monotherapy with either the biosimilar or reference drug until one of the following outcomes occurred: disease progression, excessive toxicity, withdrawal of consent, or study completion. The objective response rate (ORR) at week 19 was designated to be the primary endpoint; the ORR comprised those attaining complete or partial responses.

Variable

PF-06439535
(N=358)

EU-Licensed Avastin
(N=361)

Overall Response Rate

45.2%

44.6%

Progressive Disease

4.2%

3.9%

Progression-Free Survival (Median)

9.5 mo

7.7 mo

Nearly all study participants had an adverse event (97% in both groups); 48% in the biosimilar group and EU-licensed Avastin group experienced a grade ≥3 adverse event. The rate of immunogenicity was comparable as well for both study populations.

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

Phase 1 Study Results

A Pharmacokinetic Study Comparing PF-06439535 And Bevacizumab In Healthy Male Volunteers (REFLECTIONS B739-01)

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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