Ogivri

Product Profile:

Trastuzumab-dkst (Ogivri)

Drug Category: HER2/neu receptor antagonist

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

Co-developed by Biocon and Mylan; Will be marketed by Mylan in the US

Summary:  Ogivri is a biosimilar version of trastuzumab (reference product, Herceptin, Roche, Inc.) developed and manufactured by the team of Biocon and Mylan.

A biologic license application for approval via the 351(k) biosimilar pathway was submitted to the Food and Drug Administration (FDA) in November 2016. It received a unanimous recommendation for approval from the FDA’s Oncology Drug Advisory Committee; formal approval was received December 3, 2017. The drug has not yet been launched in the US, because of a licensing agreement Mylan signed with Roche. A launch date has not been announced, but speculation is that this date will be in 2019 or 2020.

About the Manufacturer

The partners Mylan and Biocon are very active in the biosimilar space. Mylan is a US-based company that focuses on generics and specialty pharmaceuticals. Biocon is an Indian pharmaceutical company thatmanufactures and commercializes complex generics, biosimilars, insulins, and novel biologics. Their global partnership in biosimilars includes the approved products Ogivri and the pegfilgrastim biosimilar Fulphila, in addition to nine other biosimilars and insulin agents (not all of these agents will be targeted for US FDA approval).

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Ogivri is the first trastuzumab biosimilar to be approved by the FDA. The product has not yet entered the marketplace.

Trastuzumab Biosimilar(s) in Development

Currently, at least 5 trastuzumab biosimilars have been reviewed by the FDA. Ogivri (Mylan/Biocon), Herzuma (Celltrion/Teva), Ontruzant (Samsung Bioepis/Merck), Trazimera (Pfizer), and Kanjinti (Amgen) have been approved to date, but Kanjinti is the only trastuzumab biosimilar to be marketed. The other manufacturers have licensing agreements in place with the manufacturer of the reference product (Roche); their launch dates have not been announced, despite the fact that the principal patents on Herceptin have expired.

TRASTUZUMAB APPROVED BY THE FDA: FDA FILING DATES AND ACTIONS

Manufacturer

Brand Name & Designation

FDA Filing Data

Status

Celltrion/Teva

Herzuma (trastuzumab-pkrb)

July 2017

FDA approved December 14, 2018

Mylan/Biocon

Ogivri (trastuzumab-dkst) 

November 2016

FDA approved December 2017

Samsung Bioepsis/Merck

Ontruzant (trastuzumab-dttb)

December 2017

FDA approved  January 21, 2019

Amgen

Kanjinti (trastuzumab-anns)

August 2017

FDA Approved June 13, 2019

TRATUZUMAB BIOSIMILARS IN DEVELOPMENT

Company Name

Product Name

Stage of Development

Eirgenix/Sandoz

EG12014

Phase 3 trial to be completed in 2021. Eirgenix signed commercialization agreement in 2019 with Sandoz for global markets excluding Taiwan and China

Amgen/Allergan Partners Announce Launches of Herceptin and Avastin Biosimilars

(July 19, 2019) Amgen has announced 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.

Samsung Bioepis Signals a Settlement With Genentech on Herceptin Biosimilar

(July 12, 2019) Samsung Bioepis and Genentech filed a motion in District Court to drop all pending patent litigation regarding Ontruzant®, an approved Herceptin® biosimilar.

Don’t Expect All-Out Biosimilar Competition for Herceptin—Just Yet

(June 17, 2019) According to Goodwin’s Big Molecule Watch, Roche’s infringement claims against Samsung Bioepis (Ontrusant®) and Amgen/Allergan (Kanjinti®) are still being litigated. For Genentech v. Samsung, the bench trial is slated to begin December 9, 2019.

Amgen/Allergan Receive FDA Approval for Their Biosimilar Version of Herceptin

(June 14, 2019) On June 13, the Food and Drug Administration (FDA) approved the fifth trastuzumab biosimilar. This product, Kanjinti (trastuzumab-anns), will be produced through the partnership of Amgen and Allergan.

Pfizer Gains Approval for Trazimera, the Fourth Trastuzumab Biosimilar

(March 11, 2019) A fourth trastuzumab biosimilar has been approved by the US Food and Drug Administration (FDA). Pfizer’s biosimilar version of trastuzumab-qyyp (Trazimera) gained approval on March 11.

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 Ogivri

Clinical Trial Results

Effect of a proposed trastuzumab biosimilar compared with trastuzumab on overall response rate in patients with ERBB2 (HER2)-positive metastatic breast cancer: A randomized clinical trial.

This phase 3, multicenter, randomized, parallel-group trial tested Ogivri versus the EU-licensed version of Herceptin. The manufacturers had also provided bridging studies to prove the equivalence of the US- to EU-licensed reference product.

The researchers’ primary endpoint for this study was overall response rate (ORR) at 24 weeks in patients with metastatic breast cancer who are also receiving taxane therapy. The secondary endpoints of progression-free survival (PFS) and safety and immunogenicity were also analyzed. The primary data analysis was performed on the intent-to-treat population. If patients experienced stable disease (SD), a complete or partial response, they were enrolled in a 24-week extension trial, in which their trastuzumab medications were given without taxanes once every three weeks until a 48-week cut-off.

The intent-to-treat population comprised 458 patients (230 in the biosimilar arm and 228 in the reference product or control arm). Patients in the biosimilar arm demonstrated an ORR of 70% compared with 64% in the control arm, which was within the predefined equivalence range. The median duration of response was 9.7 months (after 48 wk) for both treatment arms.

Results in the Intent-to-treat population:

  Ogivri + Taxane EU-Herceptin + Taxane
Complete Response 2% 0%
Partial Response 68% 64%
Overall Response Rate 70% 64%
Stable Disease 21% 21%
Overall Survival 89% 85%
Progression-Free Survival 44% 45%
Adverse Events 97% 95%
Neutropenia 57% 53%
Grade 3/4 Adverse Events 63% 63%
Antidrug Antibody Presence 2.4% 2.8%
None of these differences were statistically significant.

The investigators concluded that Ogivri and EU-licensed Herceptin yielded equivalent clinical and safety outcomes, and there were no meaningful differences between the drugs with respect to drug safety.

Current ongoing trials: None.

Phase 1 trials:

Phase 1 Study of Trastuzumab Administered as a Single Intravenous Infusion

Study results: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM566369.pdf

Important Links and Resources

Information About Biosimilars

Patient Assistance Information

Additional Patient Assistance Resource

US Biosimilar Filings Status

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