HONG KONG – HKEX-listed Innovent Biologics Inc. said its IBI-305 referencing Roche Holding AG's Avastin (bevacizumab) has met primary endpoints in two randomized, head-to-head trials, putting the company one step closer to bringing to market one of the first Avastin biosimilars approved in China.

An injectable drug candidate, IBI-305 is a recombinant humanized anti-VEGF monoclonal antibody to treat EGFR-TKI failure non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC).

"The results of the trials have shown a high similarity between IBI-305 and Avastin," Michael Yu, Innovent's CEO, told BioWorld. "The next step is to file an NDA with China's National Medical Products Administration [NMPA, formerly the CFDA] in the first quarter of 2019."

Currently, Innovent is tight-lipped about the details, but Yu revealed that the company will disclose more at an international conference in the first half of next year.

What is known so far is that IB-I305 has met the primary endpoint, which is objective response rate, in CIBI305A301, a phase III, multicenter, randomized, double-blinded, parallel, positive-controlled study in patients with advanced nonsquamous NSCLC. The study began in November 2016.

With 450 patients enrolled, the study compared the efficacy, safety and immunogenicity between IBI-305 and Avastin in combination with paclitaxel/carboplatin in first-line treatment. Randomized at a 1-to-1 ratio to two treatment arms, the patients received 15 mg/kg of both agents in combination with paclitaxel/carboplatin for six cycles, then maintained the dosage at 7.5 mg/kg.

According to Innovent's prospectus in October, the blinded analysis of the interim trial data show the safety profile of IBI-305 is consistent with the reported safety profile for Avastin.

Innovent has yet to disclose any results for the secondary endpoints, which are the overall survival time and progression-free survival.

IBI-305 also met the primary endpoint in a smaller pharmacokinetic study that has demonstrated bioequivalence between Avastin and the biosimilar. That study, known as CIBI305A201, is a randomized, double-blinded, parallel, positive-controlled single-dose trial in 100 healthy subjects that started in March 2017 in China. It aims to assess the pharmacokinetic profile, safety, tolerability and immunogenicity of a single 3-mg/kg dose of IBI-305 compared to Avastin in the patients.

"The primary endpoints of AUC0-inf [extrapolated total area under plasma curve to time infinity] and AUC0-t [area under the plasma concentration time curve], as well as Cmax [the peak serum concentration that a drug achieves in a test area of the body after drug administration], t½ [half-life], drug clearance and volume of distribution, were similar for IBI-305 and Avastin at a 3-mg/kg dose level," Innovent said in its prospectus.

The company added that for each of AUC0-inf and AUC0-t, the 90 percent confidence intervals for the ratio of IBI-305 to Avastin were fully contained within 80 percent to 125 percent. The result demonstrated bioequivalence between the biosimilar and Avastin. "The pharmacokinetic profile plots demonstrated substantial overlap for the profile of IBI-305 and Avastin out to 2,000 hours after a single dose administration in normal volunteers."

Innovent submitted an IND application for IBI-305 to the NMPA in December 2014, and the approval came in May 2016.

In October, the company also got IND clearance to test the combination of IBI-305 and its anti-PD-1 monoclonal antibody, IBI-308 (sintilimab), to treat NSCLC and HCC.

Fierce competition

Competition in the anti-VEGF area for treating NSCLC is fierce in China. To date, there are seven other Avastin biosimilars in phase III trials, and one drug candidate has reached the NDA submission stage. In August, the NMPA accepted an NDA from Jinan-based Qilu Pharmaceutical Co. Ltd. for its QL-1101 and put it under the priority review pathway in October.

"By the end of this year, the biosimilar to Avastin will be the first to be approved in China," predicted Andrew Yu, director at strategy consultancy Monitor Deloitte's China Life Science Practice. (See BioWorld, Oct. 10, 2018)

Other competitors in the race include Shanghai Henlius Biotech Inc.'s HLK-04, Genor Biopharma Co. Ltd.'s GB-222, Beijing Mabworks Biotech Co. Ltd.'s MIL-60, Luye Pharma Group Ltd.'s LY-01008, Jiangsu Hengrui Medicine Co. Ltd.'s BP-102, Tot Biopharm Co. Ltd.'s TAB-008 and Bio-Thera Solutions Ltd.'s BAT-1706.

Since 2015, Roche's Avastin has been approved in China as a first-line treatment of advanced metastatic nonsquamous NSCLC, after it was first allowed in the country to treat metastatic colon and rectal cancers in 2010.

The China sales of Avastin were ¥1.7 billion (US$246.4 million) in 2017 and are expected to reach ¥8.8 billion in 2022 and ¥16.6 billion in 2030.

On Dec. 14, Innovent's shares (HKG:1801) fell 1.9 percent to HK$20.95 (US$2.68). Innovent remains the only Hong Kong-listed pre-profit biotech that is holding above its IPO price. (See BioWorld, Nov. 1, 2018.)

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