Henlius’ Pertuzumab Biosimilar Exhibits Comparable PK Profile to Reference Product in First Human Research

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

In a part 1 scientific trial, the primary human examine of the pertuzumab biosimilar candidate HLX11(Shanghai Henlius Biotech), investigators discovered pharmacokinetic (PK) parameters, security, and immunogenicity have been much like the US, EU, and China model of the reference product following a single dose in wholesome male adults in China.

Within the examine revealed in BioDrugs, the authors cited stories that the incidence of breast most cancers worldwide is growing, and 15% to twenty% of sufferers have HER2-positive breast most cancers, wherein human epidermal development issue receptor 2 (HER2) is amplified or overexpressed. HER2-positive most cancers contributes to poor prognosis. Nonetheless, anti-HER2 remedy “has considerably improved scientific outcomes for sufferers with HER2-positive breast most cancers,” they wrote.

The reference pertuzumab (Perjeta) and trastuzumab, 2 monoclonal antibodies to HER2 that bind to totally different epitopes, are ceaselessly used as mixture remedy to deal with HER2-positive breast most cancers, leading to “a extra full blockade of HER2 signaling than trastuzumab monotherapy.” The authors stated that pertuzumab and trastuzumab mixture remedy is “underused worldwide,” and the event of biosimilars might present cost-effective alternate options and enhance entry to remedy. Perjeta was licensed in the US, European Union, and China in 2012, 2015, and 2018, respectively.

The individuals have been randomized to obtain HLX11 or the reference product from the US, European Union, or China. They got a single intravenous dose of pertuzumab and remained on the examine website for five days. They returned for follow-up checks on days 8, 15, 29, 50, 71, and 99.

Pharmacokinetic Parameters Comparable in All 4 Teams

The typical serum focus of HLX11 was much like these of the three variations of the reference product, with no important variations between medication at any time level. Further serum pharmacokinetic parameters together with Cmax (most noticed drug focus within the plasma) and Tmax (time to succeed in most serum focus), have been additionally related between teams.

In pairwise comparisons between HLX11 and every reference product, geometric imply ratios of the first PK parameters – Cmax, space underneath the serum concentration-time curve (AUC) from time 0 to time of the final quantifiable focus, and AUC from time 0 to infinity – have been throughout the prespecified equivalence margins of 80% to 125%.


Most sufferers (97.5% within the biosimilar, US reference, and EU reference teams, and 90% within the China reference group) skilled at the least 1 treatment-emergent hostile occasion (TEAE). The commonest TEAEs have been leukocytosis (54.4%), proteinuria (36.9%), hypertriglyceridemia (30.6%), urinary tract an infection (28.1%), diarrhea (26.3%), mouth ulceration (18.8%), and hyperuricemia (15.6%).

Most TEAEs have been grade 1 or 2, there have been grade 3 TEAEs in 4 (2.5%) individuals, and there have been no grade 4 or 5 TEAEs. Grade 3 TEAEs included transient elevations in triglycerides, 1 participant within the HLX11 group and 1 within the EU pertuzumab reference product group. Additionally, 1 affected person within the US reference group skilled a duodenal ulcer, and 1 affected person within the China reference group skilled transient proteinuria.

Anti-Drug Antibodies

By the top of follow-up (day 99), anti-drug antibodies (ADAs) have been detected in 62.5%, 37.5%, 37.5%, and 37.5% of individuals within the HLX11, US reference pertuzumab, EU reference, and China reference teams, respectively. Charges of neutralizing antibodies “have been low and comparable throughout teams,” in response to the authors, at 0%, 2.5%, 7.5%, and a couple of.5% in every of the 4 respective teams.

Evaluation of the imply drug focus in serum over time with respect to ADAs and neutralizing antibodies instructed “immunogenicity had no impact on the plasma focus within the totally different remedy teams.” Equally, the investigators reported, PK parameters and hostile occasions didn’t differ between ADA-positive and ADA-negative individuals.

First Human Research of HLX11

On this first human examine of the pertuzumab biosimilar candidate, the authors concluded that HLX11 was similar to the three variations of the reference product by way of pharmacokinetics, security, and immunogenicity in wholesome grownup males. They stated their outcomes “help part 3 scientific examine growth of HLX11 as a pertuzumab biosimilar within the affected person inhabitants.” In addition they famous a energy of their examine was the comparability to three totally different sources of the reference biologic.


Yang J, Lin L, Lengthy Q, et al. HLX11, a proposed pertuzumab biosimilar: pharmacokinetics, immunogenicity, and security profiles in comparison with three reference biologic merchandise (US-, EU-, and CN-approved pertuzumab) administered to wholesome male topics. BioDrugs. 2022;36:393-409. doi:10.1007/s40259-022-00534-w

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