Based on China to Go International: The Trastuzumab Biosimilar HLX02 Applied for Marketing

According to the announcement of Henlius on Apr. 25, 2019, the marketing application of the trastuzumab HLX02 has been accepted by NMPA, with the acceptance No. of CXSS1900021 and the indications applied for being early-stage HER2+ breast cancer, metastatic breast cancer, and metastatic gastric cancer. HLX02 is one of the 4 core products of Henlius and is being conducted a global Phase 3 clinical trial in China, Poland, Ukraine, and the Philippines. The marketing of the drug in China will mark a milestone of the product’s development and commercialization. Roche’s trastuzumab has so far been marketed for 21 years in the world and 17 years in China, with global sales reaching CHF6.982 billion and sales in China reaching about RMB2.7 billion in 2018. The marketing of HLX02 in China will benefit more cancer patients to effectively reduce patients’ medical payment pressure!

This article describes the development process of HLX02 and summarizes the key development nodes of the drug according to the data disclosed by Henlius.

1. HLX02: trastuzumab from China to the world

As one of the 4 core products (HLX01, 02, 03, 04) of Henlius, trastuzumab HLX02 project was commenced in May 2011 and has taken 8 years so far. HLX02 has become the first biosimilar developed in China and conducted Phase 3 clinical trial in many regions in the world (China and the Philippines in Asia, and Poland and Ukraine in Europe). And Henlius has entered into cooperation agreements for commercialization of the drug with Accord, Cipla, and Jacobson, to further accelerate the internationalization process of the drug.

Development progress of Phase 1 and Phase 3 clinical trials of HLX02:

Data reference: Drug Clinical Trial Registration and Information Publicity Platform of CDE

According to the information queried, HLX02 has two registered clinical trials, separately CTR20150642 and CTR20160526, wherein:

CTR20150642

Professional title: A Phase I clinical trial to evaluate the safety and tolerance of different doses of HLX02 and the pharmacokinetic characteristics, safety, tolerance, and immunogenicity of HLX02 and Herceptin

Enrolled patients: 123

The first patient enrolled on: Sep. 22, 2015

Completed on: May 11, 2016

Design of the trial as follows:

The Phase 1 clinical trial is divided into two parts, i.e., part 1 is open, dose arising trial, with 12 Chinese healthy males to accept 2, 4, 6 and 8 mg/kg single-dose HLX02. According to the data, HLX02’s pharmacokinetics showed a positive correlation with the dose, and different doses of the drug all showed good tolerance.

Part 2 of the trial is a multicenter, randomized, and double-blind study, with 111 patients grouped according to 1:1:1 to separately receive 6 mg/kg HLX02, Herceptin sold in China, and Herceptin sold in the EU. According to the data, AUC_0-inf (90% CI) geometric mean was separately 0.914, 0.950, and 0.962 in patients using HLX02, Herceptin sold in China, and Herceptin sold in the EU; the 90% CIs of the means were bounded within the predefined bioequivalence criterion of 80% to 125%.

Drug safety: Good

In part 1 of the trial, 8 adverse reactions were reported and all were treatment emergent adverse event (TEAE), including 7 ADRs, commonly: glutamic-pyruvic transaminase elevation, drowsiness, and dizziness, without SAE, withdrawal from treatment, or death;

In part 2 of the trial, the safety results of the 3 groups had comparability, without statistical differences, and without adverse event above CTCAE grade III, death, or serious adverse event (SAE) detected.

The immunogenicity was good. Among the 3 treated group in part 2, the ADA detection results were all negative.

1. CTR20160526: A multicenter clinical trial that is underway

Professional title: A Phase 3 clinical trial to compare the efficacy, safety, and immunogenicity in untreated HER2+ metastatic breast cancer treated with HLX02 and Herceptin

The first patient was enrolled for CTR20160526 on Nov. 11, 2016, and the patient recruitment was completed in June 2018. The trial is still underway. The clinical trial is supported by China’s National S&T Major Project for Major New Drug Invention during the 13th Five-year Plan period and among the S&T Supported Projects in the Biomedical Field of the Science and Technology Innovation Action Plan, with the project No.: 2018ZX09736016; 16431901300.

The indication of the Phase 3 clinical trial is untreated HER2+ metastatic breast cancer, and the indication in the marketing application is extended to early-stage HER2+ breast cancer and HER+ metastatic gastric cancer. The clinical trial results have not been published, which sustained attention can be paid to.

2. Important development nodes of trastuzumab HLX02

Related:

Super-blockbuster: Trastuzumab

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