Shanghai Henlius Biotech, Inc. has achieved a significant milestone as the U.S. Food and Drug Administration (FDA) accepts their Biologics License Application (BLA) for HLX11, a biosimilar to pertuzumab (Perjeta), targeting HER2-positive breast cancer treatment.
Clinical Evidence Supporting the Application
The BLA submission is backed by robust data from multiple clinical studies, including analytical similarity assessments and comparative trials. A pivotal phase 1 study (NCT04411550) evaluated the drug's fundamental characteristics in healthy Chinese male subjects, while a large-scale phase 3 trial (NCT05346224) assessed its efficacy in the target patient population.
The phase 1 study yielded promising results, demonstrating that HLX11's pharmacokinetic profile aligned closely with reference pertuzumab versions from the US, European Union, and China. Key measurements, including maximum serum drug concentration and area under the serum concentration-time curve, met pre-established equivalence margins.
Safety data from the phase 1 trial showed comparable profiles across all treatment arms, with 95.6% of participants experiencing treatment-emergent adverse effects (TEAEs), predominantly grade 1 or 2 in severity. The study utilized a balanced design, randomly assigning 40 participants to each of the four treatment arms, with all receiving 420 mg intravenous doses.
Phase 3 Trial Design and Outcomes
The larger phase 3 study, involving approximately 900 patients, focused on HER2-positive, hormone receptor-negative early or locally advanced breast cancer. This multi-center, double-blind trial achieved its primary endpoint, demonstrating equivalent total pathological complete response (tpCR) rates between HLX11 and reference pertuzumab.
Treatment protocol included an initial loading dose of 840 mg followed by 420 mg administered intravenously every three weeks. Patients also received a combination therapy including trastuzumab, docetaxel, and chemotherapy with doxorubicin and cyclophosphamide in the neoadjuvant setting.
Regulatory Progress
The development program has already gained traction in China, where the National Medical Products Administration accepted a new drug application for HLX11 in December 2024. The application covers both early breast cancer treatment in combination with trastuzumab/chemotherapy and metastatic or locally recurrent breast cancer in combination with trastuzumab/docetaxel.
Clinical Impact and Patient Selection
The development of HLX11 addresses an important need in breast cancer treatment, specifically targeting patients with HER2-positive disease. The phase 3 trial focused on patients with tumors larger than 2 cm and excluded those with inflammatory breast cancer, stage IV disease, bilateral breast cancer, or multicentric breast cancer, defining a clear target population for the therapy.
