Trazimera

Product Profile:

Trastuzumab-qyyp (Trazimera)

Drug Category: HER2/neu receptor antagonist

Target Indications: Treatment of HER2-overexpressing breast cancer and and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma

Developed by Pfizer; Will be marketed by Pfizer

Summary: Trazimera is a biosimilar version of trastuzumab (reference product, Herceptin, Roche, Inc.) developed by Pfizer.

Originally designated PF-05280014 , a biologic license application for approval via the 351(k) biosimilar pathway was initially submitted to the Food and Drug Administration (FDA) in the third quarter of 2017. A complete response letter was issued by the FDA in April 2018, citing the need for additional technical information (not additional clinical studies). After refiling for approval later that year, it was approved by the FDA March 11, 2019 (without requiring evaluation by the FDA’s Oncology Drug Advisory Committee). This agent was approved for both of the indications held by the reference product (approved to treat HER-positive breast cancer and to treat HER-positive gastric cancer). The drug has not yet been launched in the US.

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 Nivestym, its approved biosimilars include Inflectra, the first biosimilar version of Remicade; Ixifi, another version of Remicade that will be sold overseas only; and Retacrit, a biosimilar epoetin that was approved in May 2018. Pfizer’s biosimilar pipeline consists of a biosimilar trastuzumab, bevacizumab, and rituximab, all being filed for approval with the FDA; biosimilar adalimumab in phase 3 trials; and biosimilar pegfilgrastim in phase 1 development.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Trastuzumab Biosimilar(s) Approved and in Development

Currently, at least 5 trastuzumab biosimilars, including Trazimera, have been reviewed by the FDA. Ogivri (Mylan/Biocon), Herzuma (Celltrion/Teva), Ontruzant (Samsung Bioepis/Merck), and Trazimera (Pfizer) are the only approved trastuzumab biosimilars to date. None have been marketed in the US owing to patent issues or licensing deals.

APPROVED TRASTUZUMAB BIOSIMILARS

Company name

Brand name

When filed

Approval date/Marketing Status

Mylan/Biocon

Ogivri

November 2016

December 2017; not yet marketed

Celltrion/Teva

Herzuma

July 2017/June 2018

December 2018; not yet marketed

Samsung Bioepis/Merck

Ontruzant

December 2017

January 2019; not yet marketed

Pfizer

Trazimera

Q3 2017

March 2019; not yet marketed

TRASTUZUMAB BIOSIMILARS IN DEVELOPMENT

Company name

Product name

Stage of development

Amgen/Allergan

Kanjinti

FDA approved June 2019; marketed

Pfizer Gains Approval for Trazimera, Its Trastuzumab Biosimilar

(March 11, 2019) Pfizer announced that it received approval of its trastuzumab-qyyp on March 11. Dubbed Trazimera, it is the fourth approved Herceptin biosimilar. No word was provided on when it would enter the market.

Samsung Bioepis Scores FDA Approval of Ontruzant, the Third Biosimilar Trastuzuma

(January 18, 2019) This is the third trastuzumab biosimilar approved by the FDA, following those by Mylan and Biocon in December 2017 (Ogivri®) and Teva and Celltrion last month (Herzuma).

Second Trastuzumab Biosimilar Approved, Herzuma by Celltrion

(December 14, 2018) The US Food and Drug Administration gave its approval for a new trastuzumab biosimilar (Herzuma™). Manufactured by Celltrion and marketed in the US by Teva, this agent has been designated trastuzumab-pkrb.

Pfizer Signs Licensing Agreement with Roche on Trastuzumab Biosimilar

(December 10, 2018) Pfizer joined Mylan/Biocon in signing a confidential licensing agreement with Roche that cancels any patent litigation between the companies but delays launch.

Mylan Rethinking Its US Business Strategy?

(August 9, 2018) In reporting lower earnings on its second-quarter revenues, Mylan may have surprised industry observers by offering the possibility of some changes in strategic direction.

FDA Approval Eludes Amgen for Biosimilar Trastuzumab

(June 3, 2018) Amgen will have to wait a bit longer to market its biosimilar version of trastuzumab. On Friday, June 1, the Food and Drug Administration (FDA) rejected Amgen’s 351(k) application for its Herceptin® biosimilar.

Trastuzumab Dosing May Be Given in Half the Time: Will Costs/Revenues Be Cut as Well?

(May 18, 2018) A presentation at the annual American Society of Clinical Oncology (ASCO) meeting promised equal efficacy and much improved safety for patients with early-stage breast cancer receiving a 6-month instead of 12-month regimen of trastuzumab®.

Pfizer Receives FDA Rejection on Trastuzumab, Next up Is Amgen/Allergan

(April 24, 2018) When Pfizer announced that it received a complete response letter from the Food and Drug Administration (FDA), the wait for an available biosimilar to Herceptin®just got longer..

Teva and Celltrion Receive Rejections on Trastuzumab and Rituximab Biosimilars

(April 5, 2018) Celltrion and its partner Teva were dealt a significant blow today, as the Korean manufacturer announced that the latest two biosimilar candidates were rejected by the Food and Drug Administration.

Mylan/Biocon Receive First Approval for Trastuzumab Biosimilar, but First to Market?

(December 3, 2017) On December 1, the team of Mylan and Biocon received their first biosimilar approval in the US, for an agent to compete with Roche’s Herceptin®. The approval decision on this product was delayed 3 months owing to potential issues involving Biocon’s manufacturing facility. However, this marks the first biosimilar approved for trastuzumab, beating entries from Amgen/Allergan and Celltrion to the 351(k) finish line.

Mylan Clears the Way to Potential Trastuzumab Biosimilar Launch

(March 3, 2017) A settlement reached with Genentech and F. Hoffmann-La Roche Ltd. should allow Mylan to launch its biosimilar version of Herceptin® soon after the completion of its Food and Drug Administration (FDA) review in September.

What Is HER2-Positive Breast Cancer?

The Basics of Biosimilars

Clinical Trials of Trazimera

Phase 3 Trials

PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study.

A randomized, double-blind study was undertaken to compare the clinical efficacy and safety of PF-05280014 with EU-licensed Herceptin® as first-line treatment in patients with HER2-positive metastatic breast cancer.

A total of 707 patients were assigned to receive either the biosimilar (352 patients) or reference drug (355 patients) in addition to paclitaxel. Study doses were identical between the study and comparison group, with trastuzumab 4 mg/kg given initially, then 2 mg/kg administered thereafter until week 33, when clinicians had the option to change to 6 mg/kg every 3 weeks. Paclitaxel doses were given on days 1, 8, and 15 of each 28-day treatment cycle (≥ 6 cycles). Objective response rate at week 25 was the primary endpoint.

The researchers found that the objective response rates were 62.5% for the group given the biosimilar and 66.5% for those given the originator drug. They did not find any meaningful difference in progression-free survival (12.16 vs. 12.06 mo, respectively) or one-year overall survival (89.3% vs. 87.4%, respectively).

The number of treatment-emergent adverse events was equal between the treatment groups. Adverse events rated as grade 3 or above was observed in 34.4% of those in the biosimilar group and 36.5% in the reference drug group.

On the basis of these findings, the researchers concluded that PF-05280014 plus paclitaxel resulted in equivalent outcomes compared with EU-licensed Herceptin plus paclitaxel.

A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)

In this phase 3 study, investigators compared the pharmacokinetics of PF-05280014 with EU-licensed Herceptin, when both were given in combination with carboplatin and Taxotere before resection in patients with HER2-positive breast cancer. Secondary endpoints included clinical response rates and safety.

Loading doses of 8 mg/kg of either trastuzumab medication were given to patients, followed by 6 mg/kg every three weeks. Taxotere and carboplatin doses were identical between study groups. A total of 109 patients in the biosimilar trastuzumab group and 106 patients in the reference drug group completed the study (114 and 112 patients were enrolled, respectively).

The researchers found that the percent of patients with steady state levels of the biosimilar was not inferior to those taking the EU-licensed reference drug after the fifth chemotherapy cycle. The second pharmacokinetic outcome, mean predose biosimilar trastuzumab and reference trastuzumab concentrations at cycles 1 through 6 also displayed similar profiles.

Pathologic complete responses were observed in 47% and 50% in the PF-05280014 and Herceptin groups; objective responses were seen 88% and 82%, respectively. The researchers found only one patient (in cycle 1 only) of the reference drug group who demonstrated antidrug antibodies; neutralizing antibodies were not seen in any study patients.

Phase 1 Studies

A Study Evaluating The Safety Of PF-05280014 And Trastuzumab In Healthy Male Volunteers (REFLECTIONS B327-06)

A randomized phase 1 pharmacokinetic trial comparing the potential biosimilar PF-05280014 with trastuzumab in healthy volunteers (REFLECTIONS B327-01)

Important Links and Resources

Information About Biosimilars

Patient Assistance Information*

US Biosimilar Filings Status

*This product is not yet available for prescription.

Copyright 2019 by SM Health Communications. All rights reserved.

We are pleased to hear your questions or comments, which should be provided through our contact us page.