Chinese biosimilar maker Shanghai Henlius Biotech Inc. won EMA approval for its Zercepac, a biosimilar to Roche Holding AG’s Herceptin (trastuzumab) on July 28. Henlius CEO Scott Liu told BioWorld that Zercepac will be the first Chinese monoclonal antibody biosimilar to enter the EU market, setting a precedent for Chinese drugmakers seeking to join the global race in biosimilars.
“The technical thresholds for developing and manufacturing biosimilars are high,” Liu said. “There are only a handful of biopharmaceutical companies in the world capable of entering the EU and U.S. markets to compete. He added that the EU approval was an important milestone in the Chinese company’s global product development strategy.
Zercepac was developed and manufactured by Henlius. It is now cleared for HER2-positive early breast cancer, HER2-positive metastatic breast cancer and HER2-positive metastatic gastric cancer in the EU. The biosimilar also is under review in China, and Henlius expects approval this year, which would make Zercepac the first homegrown Herceptin biosimilar cleared in China.
Henlius sought EU clearance for its drug through U.K.-based commercialization partner Accord Healthcare Ltd. The approval came a little more than a year after the MAA of Zercepac was accepted in June 2019.
Following the EU approval, Accord will be exclusively commercializing Zercepac in 53 countries in Europe. In return, Henlius will receive up to $40.5 million as an up-front payment and milestone fees, plus net profits from Zercepac ranging from 15% to 26.5% as royalties, according to the amended agreement in June.
"The EMA’s positive opinion on Zercepac was based on the review of a series of research data,” said Liu. “A number of head-to-head studies have been carried out with trastuzumab, including comparative quality studies, preclinical studies, a phase I clinical trial, and a global multicenter phase III clinical trial in April 2020.”
Known as HLX-02 in Henlius’ pipeline, the drug was compared to EU-marketed originator Herceptin in a randomized, double-blind, phase III trial. Henlius said last October that HLX-02 met primary endpoints in the trial, and results confirmed that the biosimilar candidate has no significant clinical difference in efficacy and safety from Herceptin.
Zercepac is the first biosimilar developed in China to go up for approval in the EU and China simultaneously. It is also the first biosimilar developed in China to enter global phase III trials in China, Poland, Ukraine and the Philippines. The study enrolled 649 treatment-naive patients with recurrent HER2-positive or metastatic breast cancer from 89 research centers in those countries.
In addition to the positive data, Henlius worked to meet EU standards for its manufacturing site for Zercepac. In April, its drug substance line and drug product line for Zercepac passed the GMP on-site inspection by the EU.
Joining the global race
Henlius’ success in the EU market has boosted the confidence of Chinese biologics developers who aim to go global. Analysts in China have also predicted that the country will export more biologics to the overseas markets, instead of the current exports of mainly active pharmaceutical ingredients and generics, as more Chinese drugmakers turn to biologics and efforts start to bear fruit.
For biosimilars, in particular, China has been an active player in the global race. According to data from Clarivate, China has more than 110 biosimilars under development, out of 290 biosimilars in the development and NDA-ready stage in the world.
Last year, Bio-Thera Solutions Ltd. and Qilu Pharmaceutical Co. Ltd. won NMPA approvals for their biosimilars referencing Humira (adalimumab, Abbvie Inc.) and Avastin (bevacizumab, Roche Holding AG), respectively.
Competition in biosimilars only gets fiercer at home. Meanwhile, Chinese drugmakers are also launching more overseas trials. They launched 23 clinical trials in Europe in 2018, a sharp increase from only four trials in 2015. The number of U.S. trials conducted by Chinese players also jumped from 15 to 60 during the same period.
“We have recently seen Chinese companies bring biopharmaceutical products to market and there are many more in clinical trials that we expect to reach the market within the next several years,” Scott Wheelwright, founder of consulting firm Complya Asia Co. Ltd., told BioWorld.
“Chinese companies that are developing biopharmaceuticals, including both biosimilars and novel products, are conducting clinical trials in Europe and the U.S. with an eye toward sales in these markets, usually through an established partner,” he added.
In the case of Henlius, time will tell how well the Chinese product can compete with other Herceptin biosimilars in the EU, as the EMA has also approved Pfizer Inc.’s Trazimera, Samsung Bioepis Co. Ltd.’s Ontruzant, Celltrion Inc.’s Herzuma, Amgen Inc. and Allergan plc’s Kanjinti, as well as Mylan NV and Biocon Ltd.’s Ogivri. Meanwhile, Prestige Biopharma Pte. Ltd.’s Tuznue is under review.