Trastuzumab Biosimilar Ogivri Launches in United States

The trastuzumab biosimilar Ogivri (MYL-1401O; trastuzumab-dkst) has been launched in the United States for all indications of the reference product, including the treatment of patients with HER2-overexpressing breast cancer and metastatic gastric or gastroesophageal junction adenocarcinoma.

Hope Rugo, MD

The trastuzumab (Herceptin) biosimilar Ogivri (MYL-1401O; trastuzumab-dkst) has been launched in the United States for all indications of the reference product, including the treatment of patients with HER2-overexpressing breast cancer and metastatic gastric or gastroesophageal junction adenocarcinoma.1

The biosimilar is available in a 420-mg multi-dose vial and 150-mg single-dose vital in an effort to provide patient dosing and treatment flexibility, according to Mylan and Biocon Ltd., which codevelop Ogivri.

“Trastuzumab-dkst has many firsts to its credit. It was one of the first biosimilar oncology products to get a unanimous approval vote at an ODAC meeting, and it was the first biosimilar study to be published in the Journal of the American Medical Association,” Hope S. Rugo, MD, professor of medicine, director of Breast Oncology and Clinical Trials Education, at the University of California, San Francisco, and lead author of the HERiTAge study, stated in a press release. "In this context, the HERITAGE study had a unique trial design that not only evaluated objective response rate at week 24 as its primary endpoint but also assessed key endpoints including progression-free survival rate and overall survival at 36 months.”

“The concordant efficacy data across all 3 endpoints conclusively demonstrated that Ogivri was similar to Herceptin, and patients without progression now continue on Ogivri as maintenance therapy,” Rugo continued. “We are pleased that patients with HER2-positive cancers now have an additional treatment option backed by robust safety and efficacy data, including long-term 36-month data. The worldwide introduction of this agent has already improved access to trastuzumab."

In December 2017, the FDA approved Ogivri for the same indications as trastuzumab, which include HER2-positive patients with breast cancer or metastatic gastric or gastroesophageal junction adenocarcinoma.2

The approval was supported by phase III results from the HERiTAge trial, a 2-part, multicenter, double-blind, randomized, parallel-group study. Patients with measurable HER2-positive metastatic breast cancer who had not received prior chemotherapy or trastuzumab for metastatic disease were randomly assigned to MYL-1401O (n = 230) or trastuzumab with docetaxel or paclitaxel (n = 228).

Patients underwent a minimum of 8 cycles in Part 1 of the trial, with trastuzumab continuing until progression. Both forms of trastuzumab were administered with a loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg every 3 weeks.

In Part 2, patients who had stable disease or better could continue with MYL-1401O or trastuzumab. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), time to progression, safety, and tolerability.

MYL-1401O demonstrated an ORR after 24 weeks of 69.6% among women who received the biosimilar in combination with a taxane compared with a 64% ORR for patients who took trastuzumab plus a taxane.3 The ratio of ORR for MYL-1401O to trastuzumab was 1.09—both 90% CI (0.974-1.211) and 95% CI (0.954-1.237). The difference in ORR between the 2 arms was 6.0% (90% CI, -1.3%-13.2%). At the week 48 cutoff, the median duration of response was 9.7 months in both groups.

In the per protocol population, ORR was 70% for MYL-1401O compared with 67% for trastuzumab. The ratio of ORR was 1.06 (90% CI, 0.96-1.18).

PFS was nearly identical between the 2 groups (stratified HR, 0.95; 95% CI, 0.71-1.25); median OS had not been met in either group.

Regarding safety, these data were also comparable. Serious adverse events (AEs) occurred in 39.3% of the patients in the MYL-1401O arm compared with 37.0% in the trastuzumab arm, with neutropenia as the most frequently reported serious AE in both arms (57.5% vs 54.1%, respectively).

Further HERiTAge results that were presented at the 2018 ASCO Annual Meeting showed that the addition of MYL-1401O to a taxane as first-line therapy followed by MYL-1401O maintenance mirrored the progression-free survival rate at 48 weeks compared with trastuzumab in patients with HER2-positive metastatic breast cancer.4

Over the course of 48 weeks, the PFS was similar at 11.1 months (P = .842) and reflected similar confidence intervals (MYL-1401O, 8.81-11.20; trastuzumab reference, 8.60-11.20). The hazard ratio graded by taxane, tumor progression, and tumor endocrine status for 48-week PFS was 0.95 (95% CI, 0.714-1.251; P = .694).

The application for the approval also included a single-dose, randomized, double-blind, comparative MYL-HER-1002 pharmacokinetic study, as well as 2 nonclinical animal studies—a single-dose comparative pharmacokinetic study in cynomolgus monkeys comparing MYL-1401O to EU-trastuzumab, and a 4-week, repeat-dose toxicity and toxicokinetic study in cynomolgus monkeys comparing MYL-14010 to EU-trastuzumab.

"As one of the largest suppliers of oncology medicines in the [United States], we are proud to offer Ogivri, biosimilar trastuzumab, in both the 420-mg and 150-mg strengths and help increase more affordable access to this important treatment option for breast and gastric cancer patients,” Rajiv Malik, president of Mylan, stated in a press release. “With regulatory approval for our biosimilar trastuzumab in more than 80 countries worldwide, we are bringing vast global biosimilars experience to the United States and look forward to continuing our work with all stakeholders in the healthcare system to reduce costs, improve access and advance care. With Ogivri, Fulphila, and our generic oncology portfolio, Mylan is uniquely positioned to provide a broad range of treatment options for oncology patients.”

Additionally, both the trastuzumab biosimilars and reference products contain a Boxed Warning for cardiomyopathy, infusion reactions, pulmonary toxicity, and embryo-fetal toxicity.


  1. Mylan and Biocon Launch Trastuzumab Biosimilar, Ogivri™ (trastuzumab-dkst), in the U.S. Mylan and Biocon Ltd. Published December 2, 2019. Accessed December 3, 2019.
  2. FDA approves Ogivri as a biosimilar to Herceptin. FDA website. Updated December 1, 2017. Accessed February 24, 2019.
  3. Rugo HS, Barve A, Waller CF, et al. 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. JAMA. 2017;317(1):37-47. doi: 10.1001/jama.2016.18305.
  4. Manikhas A, Pennella EJ, Bondarenko I, et al. Biosimilar MYL-1401O monotherapy versus trastuzumab monotherapy after combination therapy: Toxicity, efficacy, and immunogenicity from the phase 3 HERITAGE trial. J Clin Oncol. 2018,36(suppl; abstr 110).