FDA approves trastuzumab-strf for HER2-overexpressing breast and gastric/GEJ cancer

The approval was based on a thorough submission of analytical, preclinical, and clinical data from Shanghai Henlius Biotech, which included a series of head-to-head trials with HLX 02 that generated comparative quality analytical data, a phase 1 pharmacokinetic similarity trial, and a global, multicenter, phase III trial (NCT03084237) in which HLX 02 was proven to be highly similar to reference trastuzumab in terms of quality, safety, and efficacy.

“Henlius independently developed HLX 02 in accordance with the National Medical Products Administration [NMPA], the European Medicines Agency, the FDA, and other international biosimilar guidelines. It is Henlius’ first FDA-approved product. Our patient-centered approach has led us to unwaveringly explore high-quality, effective, affordable, and accessible treatment options, and our determination to promote HLX 02 in more than 40 markets around the world is Henlius’ response to patients' concerns. We look forward to reaching more patients in North America and providing them with more cost-effective access to high-quality biologics,” Jason Zhu, executive director, chief executive officer, and chief financial officer of Henlius said in a news release.

HLX 02 is developed and manufactured by Shanghai Henlius in China and has approved indications in China, the European Union (EU), and now the United States, following prior approvals for commercialization by the European Commission and NMPA in July 2020, and August 2020, respectively.

In April 2023, the FDA accepted a biologics license application (BLA) for HLX 02 as adjuvant therapy for patients with HER2-overexpressing breast cancer, and as treatment for those with HER2-overexpressing metastatic breast cancer, and HER2-overexpressing metastatic gastric or GEJ adenocarcinoma.

The BLA was based in part on data from a randomized, double-blind, phase III trial which compared HLX 02 with reference trastuzumab across 89 centers in China, the Philippines, Poland, and Ukraine. Eligible patients with HER2-positive recurrent or metastatic breast cancer were randomly assigned 1:1 to receive HLX 02 or 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 HLX 02 (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 HLX 02 and reference trastuzumab arms, respectively, experienced serious TEAEs, and 0.6% of patients in each arm had antidrug antibodies.

“The approval of [HLX 02]—our first biosimilar to be approved in the US—marks an important milestone for Accord BioPharma in our efforts to improve access for patients,” Chrys Kokino, US president of Accord, added. “Because breast and gastric cancers are among the most common types of cancer and cancer can have a high-cost burden for patients, there is a need to provide these patients with additional treatment options that may be more affordable, such as biosimilars.”

As part of its licensing agreement with Henlius, Accord BioPharma, a specialty division of Intas Pharmaceuticals, is responsible for obtaining regulatory approval as well as commercializing and developing HLX 02 in the United States and Canada.