Henlius’ Pertuzumab Biosimilar Shows Similar PK Profile to Reference Product in First Human Study

In the first human study of Shanghai Henlius Biotech's pertuzumab biosimilar candidate (HLX11), investigators found similar pharmacokinetic (PK), safety, and immunogenicity profiles between the biosimilar and the reference product (Perjeta).

In a phase 1 clinical trial, the first human study of the pertuzumab biosimilar candidate HLX11(Shanghai Henlius Biotech), investigators found pharmacokinetic (PK) parameters, safety, and immunogenicity were similar to the US, EU, and China version of the reference product following a single dose in healthy male adults in China.

In the study published in BioDrugs, the authors cited reports that the incidence of breast cancer worldwide is increasing, and 15% to 20% of patients have HER2-positive breast cancer, in which human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed. HER2-positive cancer contributes to poor prognosis. However, anti-HER2 therapy “has significantly improved clinical outcomes for patients with HER2-positive breast cancer,” they wrote.

The reference pertuzumab (Perjeta) and trastuzumab, 2 monoclonal antibodies to HER2 that bind to different epitopes, are frequently used as combination therapy to treat HER2-positive breast cancer, resulting in “a more complete blockade of HER2 signaling than trastuzumab monotherapy.” The authors said that pertuzumab and trastuzumab combination therapy is “underused worldwide,” and the development of biosimilars could provide cost-effective alternatives and improve access to treatment. Perjeta was authorized in the United States, European Union, and China in 2012, 2015, and 2018, respectively.

The participants were randomized to receive HLX11 or the reference product from the United States, European Union, or China. They were given a single intravenous dose of pertuzumab and remained at the study site for 5 days. They returned for follow-up tests on days 8, 15, 29, 50, 71, and 99.

Pharmacokinetic Parameters Similar in All Four Groups

The average serum concentration of HLX11 was similar to those of the 3 versions of the reference product, with no significant differences between drugs at any time point. Additional serum pharmacokinetic parameters including Cmax (maximum observed drug concentration in the plasma) and Tmax (time to reach maximum serum concentration), were also similar between groups.

In pairwise comparisons between HLX11 and each reference product, geometric mean ratios of the primary PK parameters – Cmax, area under the serum concentration-time curve (AUC) from time 0 to time of the last quantifiable concentration, and AUC from time 0 to infinity – were within the prespecified equivalence margins of 80% to 125%.


Most patients (97.5% in the biosimilar, US reference, and EU reference groups, and 90% in the China reference group) experienced at least 1 treatment-emergent adverse event (TEAE). The most common TEAEs were leukocytosis (54.4%), proteinuria (36.9%), hypertriglyceridemia (30.6%), urinary tract infection (28.1%), diarrhea (26.3%), mouth ulceration (18.8%), and hyperuricemia (15.6%).

Most TEAEs were grade 1 or 2, there were grade 3 TEAEs in 4 (2.5%) participants, and there were no grade 4 or 5 TEAEs. Grade 3 TEAEs included transient elevations in triglycerides, 1 participant in the HLX11 group and 1 in the EU pertuzumab reference product group. Also, 1 patient in the US reference group experienced a duodenal ulcer, and 1 patient in the China reference group experienced transient proteinuria.

Anti-Drug Antibodies

By the end of follow-up (day 99), anti-drug antibodies (ADAs) were detected in 62.5%, 37.5%, 37.5%, and 37.5% of participants in the HLX11, US reference pertuzumab, EU reference, and China reference groups, respectively. Rates of neutralizing antibodies “were low and comparable across groups,” according to the authors, at 0%, 2.5%, 7.5%, and 2.5% in each of the 4 respective groups.

Analysis of the mean drug concentration in serum over time with respect to ADAs and neutralizing antibodies suggested “immunogenicity had no effect on the plasma concentration in the different treatment groups.” Similarly, the investigators reported, PK parameters and adverse events did not differ between ADA-positive and ADA-negative participants.

First Human Study of HLX11

In this first human study of the pertuzumab biosimilar candidate, the authors concluded that HLX11 was comparable to the 3 versions of the reference product in terms of pharmacokinetics, safety, and immunogenicity in healthy adult males. They said their results “support phase 3 clinical study development of HLX11 as a pertuzumab biosimilar in the patient population.” They also noted a strength of their study was the comparison to 3 different sources of the reference biologic.


Yang J, Lin L, Long Q, et al. 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. BioDrugs. 2022;36:393-409. doi:10.1007/s40259-022-00534-w