FDA Accepts Biologics License Application for Pertuzumab Biosimilar to Treat Breast Cancer

The FDA accepted a biologics license application (BLA) seeking approval for HLX11, an investigational biosimilar of pertuzumab (Perjeta; Genentech) for the treatment of human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).¹

3D x-ray rendering of a breast cancer tumor | Image credit: Sebastian Kaulitzki | stock.adobe.com

Pertuzumab is a humanized monoclonal antibody that attaches to the proteins in cancer cells. The HER dimerization inhibitor connects onto HER2+ cancer cells and stops the cells from growing, killing them overtime.²

Currently, pertuzumab in combination with trastuzumab (Herceptin; Genentech) and docetaxel (Taxotere; Hikma) is approved by the FDA to treat HER2+ metastatic breast cancer among individuals who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease; and in combination with trastuzumab with chemotherapy as neoadjuvant treatment of patients with HER2+, locally advanced, inflammatory, or early breast cancer (EBC; either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for EBC.³

When used together, pertuzumab plus trastuzumab provide a more complete HER2 signal blockade than trastuzumab alone, leading to synergistic effects, improved efficacy, and a better prognosis. Despite its positive outcomes, the combination drug is underused and costly, according to the study authors.⁴

HLX11, the biosimilar candidate for pertuzumab, is a glycosylated, humanized monoclonal antibody targeting HER2, composed of humanized murine variable regions and human IgG1 constant regions with 2 448-amino-acid heavy chains and 2 214-amino-acid light chains.⁴

The BLA for HLX11 is based on data from 2 comparative clinical studies that compared the pharmacokinetics, safety, efficacy, and immunogenicity of the biosimilar to pertuzumab among individuals with BC. The randomized, double-blind, 4-arm phase 1 trial (NCT04411550) included US, EU, and China-sourced pertuzumab, administered intravenously in healthy Chinese males, compared with HLX11.⁴ The multicenter, randomized, double-blind phase 3 trial (NCT05346224) included EU-sourced reference pertuzumab as a neoadjuvant therapy among individuals with HER2+, hormone receptor-negative (HR-) early, or locally advanced BC, compared with HLX11.^1,5

Results from the phase 1 study demonstrated that HLX11 was comparable to all 3 pertuzumab products in terms of pharmacokinetics and safety profiles following a single intravenous infusion in healthy males. Additionally, the biosimilar had geometric mean ratios (GMRs) for primary pharmacokinetic parameters (C_max, AUC_0-t, AUC_0-∞) ranging from 93.40% to 105.66%, all within the 80% to 125% bioequivalence range, according to the study authors.⁴

The phase 3 trial met its primary end point of total pathological complete response (tpCR) rate assessed by Independent Review Committee (IRC) among individuals treated with HLX11 in combination with trastuzumab and docetaxel every 3 weeks for 4 cycles. The secondary end points included breast pathologic complete response rate, objective response rate, event-free survival, disease-free survival, safety, pharmacokinetics, and immunogenicity.⁵

If approved, HLX11 could offer a more cost-effective alternative to pertuzumab, increasing its use.⁴

REFERENCES

1. US FDA Accepts Biologics License Application (BLA) for HLX11, Biosimilar Candidate of Perjeta® (pertuzumab). Henlius. News release. Published February 2, 2025. Accessed February 7, 2025. https://www.henlius.com/en/NewsDetails-4853-26.html

2. Pertuzumab (Perjeta). Cancer Research UK. News release. Updated January 19, 2023. Accessed February 7, 2025. https://www.cancerresearchuk.org/about-cancer/treatment/drugs/pertuzumab

3. FDA approves combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf for HER2-positive breast cancer. FDA. News release. Published June 29, 2020. Accessed February 7, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-combination-pertuzumab-trastuzumab-and-hyaluronidase-zzxf-her2-positive-breast-cancer#:~:text=On%20June%2029%2C%202020%2C%20the,the%20neoadjuvant%20and%20adjuvant%20therapies

4. HLX11, a Proposed Pertuzumab Biosimilar: Pharmacokinetics, Immunogenicity, and Safety Profiles Compared to Three Reference Biologic Products (US-, EU-, and CN-Approved Pertuzumab) Administered to Healthy Male Subjects. NIH. News release. Published May 20, 2022. Accessed February 7, 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC9148872/

Primary Endpoint Met in Phase 3 Comparative Clinical Study of Perjeta® (pertuzumab) Biosimilar Candidate HLX11. Organon. News release. Published September 30, 2024. Accessed February 7, 2025. https://www.organon.com/news/primary-endpoint-met-in-phase-3-comparative-clinical-study-of-perjeta-pertuzumab-biosimilar-candidate-hlx11/