Herzuma

Product Profile:

Trastuzumab-pkrb (Herzuma)

Drug Category: HER2/neu receptor antagonist

Target Indications: Treatment of HER2-overexpressing breast cancer

Developed by Celltrion; Will be marketed by Teva in the US

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

Originally designated CT-P6, a biologic license application for approval via the 351(k) biosimilar pathway was initially submitted to the Food and Drug Administration (FDA) in July 2017. A complete response letter was issued by the FDA, regarding manufacturing plant problems. Celltrion refiled for approval in June 2018, and it was approved by the FDA December 14, 2018 (without requiring evaluation by the FDA’s Oncology Drug Advisory Committee). This agent was approved for one of the two indications held by the reference product (approved to treat HER-positive breast cancer, not to treat HER-positive gastric cancer). The drug has not yet been launched in the US; Teva will market the product in the US once launched. In the EU, Celltrion received approval in February 2018.

About the Manufacturer

Celltrion was founded in 2002 in Incheon, South Korea. Its first biosimilar product was approved in 2013 by the European Medicines Agency. Inflectra was first approved in the US in 2016. Another biosimilar product (Truxima) was approved in November 2018, and Celltrion has several other biosimilar products in development. Celltrion and Teva partnered on two approved cancer-treating biosimilars (Truxima and Herzuma). It is partnered with Pfizer on its other approved biosimilar Inflectra (for treating autoimmune disease).

In addition, Celltrion’s pipeline includes several products at various stages of development, including adalimumab, bevacizumab, cetuximab, etanercept, palivizumab, and a subcutaneous formulation of Inflectra.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Herzuma was the second trastuzumab biosimilar to be approved by the FDA. The product has not yet entered the marketplace.

Trastuzumab Biosimilar(s) Approved and in Development

Currently, 6 trastuzumab biosimilars, including Herzuma, have been reviewed by the FDA. Ogivri (Mylan/Biocon), Herzuma (Celltrion/Teva), Ontruzant (Samsung Bioepis/Merck), Kanjinti (Amben), and Trazimera (Pfizer) are the only approved trastuzumab biosimilars to date. Kanjinti launched in July 2019, and Pfizer will be launching Trazimera in February 2020. The others have not yet 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

Amgen/Alletgan

Kanjinti

July 31, 2017

June 2019; marketed

How Did Kaiser Permanente Reach 95%+ Utilization of Biosimilar Herceptin and Avastin so Quickly?

(November 7, 2019) At this week’s GRx+Biosims meeting, two sessions with Kaiser Permanente’s executives made it startling clear—if you don’t accept rebates, the decision to move to biosimilars is simple.

Pfizer Announces Launch Dates for Rituximab and Trastuzumab Biosimilars

(October 30, 2019) At an earnings call this week, Pfizer’s CEO highlighted the impending launches of Ruxience® and Trazimera®, not long after the previously announced launch of Zirabev® (bevacizumab) at the end of this year.

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 Herzuma

Phase 3 Trial

CT-P6 Compared With Reference Trastuzumab for HER2-Positive Breast Cancer: A Randomised, Double-Blind, Active-Controlled, Phase 3 Equivalence Trial.

A multicentered, international study was conducted to test the clinical equivalence of CT-P6 (Herzuma) to the originator product Herceptin in patients with HER2-positive early-stage breast cancer.

The phase 3 trial was randomized and double-blinded, involving 112 treatment centers in 23 countries. Patients with bilateral breast cancer, those who had undergone previous breast cancer treatment, and those who were pregnant or lactating were excluded from study. A total of 549 patients were randomized to receive neoadjuvant CT-P6 (N = 271) or reference trastuzumab (N = 278) intravenously for a total of eight cycles (cycle length, 3 wk). All patients received 8 mg/kg of either the biosimilar or reference product on day 1 of cycle 1 and 6 mg/kg on day 1 of cycles 2 through 8). In addition, they received neoadjuvant docetaxel, and combination fluorouracil, epirubicin, and cyclophosphamide therapy.

All patients underwent surgery within 3 to 6 weeks of the last study drug dose during the neoadjuvant period. Postsurgery, adjuvant treatment was continued for as long as 1 year. Follow-up lasted for 3 years after enrollment of the final patient (i.e., May 2019). The investigators designated pathologic complete response as the primary efficacy endpoint.

The researchers found that 46.8% of patients receiving the biosimilar and 50.4% receiving the originator product attained pathologic complete response. This was within the prespecified margin of equivalence. Seven percent and 8% of those in the CT-P6 and Herceptin groups, respectively, reported serious treatment-emergent adverse events. There were no significant differences in serious adverse events between groups. Neutropenia was the most common side effect detected in either group.

The investigators determined that there was no clinical meaningful differences between the biosimilar and originator trastuzumab agent in the treatment of early-stage HER-2 positive breast cancer.

Phase 1 Study

Study Comparing Pharmacokinetics, Safety and Immunogenicity of CT-P6 and US-licensed Herceptin

Important Links and Resources

Information About Biosimilars

Patient Assistance Information*

US Biosimilar Filings Status

*This product is not yet available for prescription.

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