Trastuzumab Biosimilar BLA Accepted for HER2+ Breast Cancer and Gastric Cancer


The FDA has accepted a biologics license application for a proposed trastuzumab biosimilar. The therapy is being considered as adjuvant therapy for certain HER2-overexpressing cancers.

HLX02, a proposed trastuzumab (Herceptin) biosimilar, has had its biologics license application (BLA) accepted by the FDA. The treatment has been proposed as an adjuvant therapy for HER2-overexpressing breast cancer, HER2-overexpressing metastatic breast cancer, and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.1

The BLA is based on comparative structural and functional analytical data that used orthogonal techniques and head-to-head clinical studies between HLX02 and reference trastuzumab. Nonclinical studies, a phase 1 pharmacokinetic similarity study, and a global multicenter, phase 3 trial (NCT03084237) evaluating safety, efficacy, and immunogenicity for HLX02 and reference trastuzumab were also included in the BLA. Clinical results demonstrated high similarity in quality, safety, and efficacy between HLX02 and reference trastuzumab.

If approved, HLX02 would represent the third biosimilar approval for Accord BioPharma.

“The promise of HLX02's reference product—[trastuzumab]—is well documented, and we’re thrilled to announce this regulatory milestone as we work to provide patients increased options and access for treatment of serious conditions in oncology, immunology, and critical care,” Chrys Kokino, president of US BioPharma at Accord BioPharma, said in a press release. “Biosimilars are key to making health care more affordable and accessible. We’re working to develop the deepest portfolio of biosimilars to enhance the patient experience and improve the cost of care across the continuum.”

HLX02 was initially developed by Shanghai Henlius Biotech, Inc., Accord’s business partner headquartered in China. In 2021, Henlius granted Accord BioPharma the exclusive rights to develop and commercialize HLX02 in the US and Canada.

The randomized, double-blind, phase 3 trial comparing HLX02 with reference trastuzumab was conducted at 89 centers in China, the Philippines, Poland, and Ukraine.2 Eligible patients with HER2-positive recurrent or metastatic breast cancer were randomly assigned 1:1 to receive HLX02 or European Union (EU)–sourced trastuzumab (first dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for up to 12 months) in combination with intravenous docetaxel.

The primary end point of the trial was 24-week overall response rate (ORR). Investigators could declare equivalence if the 95% confidence interval of difference was within ± 13.5%. Safety and immunogenicity were assessed in patients who received at least one dose of study treatment.

Between November 11, 2016, and July 10, 2019, 649 patients were enrolled. Results showed that the 24-week ORR was 71.3% with HLX02 (n = 324) compared with 71.4% with EU-trastuzumab (n = 325), with a difference of - 0.1% (95% CI, –7% to 6.9%), falling within the prespecified equivalence margins. No statistically significant differences in secondary efficacy analyses were observed, and the safety profiles and immunogenicity of both agents were comparable. Overall, 98.8% of patients in each group experienced at least one treatment-emergent adverse effect (TEAE). A total of 23.8% and 24.9% of patients in the HLX02 and reference trastuzumab arms, respectively, experienced serious TEAEs, and 0.6% of patients in each arm had antidrug antibodies.

HLX02 was approved for commercialization by the European Commission and China’s National Medical Products Administration in July 2020 and August 2020, respectively, for the same indications as the reference product, and has over 30 approvals worldwide.

Additionally, the company plans to introduce several additional biosimilars to the US market in the next five years.


  1. Accord BioPharma announces U.S. FDA acceptance of biologics license application for proposed biosimilar trastuzumab HLX02. News release. Accord BioPharma. April 5, 2023. Accessed April 5, 2023.
  2. Xu B, Zhang Q, Sun T, et al. Efficacy, safety, and immunogenicity of HLX02 compared with reference trastuzumab in patients with recurrent or metastatic HER2-positive breast cancer: a randomized phase III equivalence trial. BioDrugs. 2021;35(3):337-350. doi:10.1007/s40259-021-00475-w
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