Skip to main content

US knocks back another Chinese PD-1 entrant

The good news for Jiangsu HengRui and its ex-China partner HLB Therapeutics is that yesterday’s FDA rejection of the first US filing for the anti-PD-1 MAb camrelizumab wasn’t apparently the result of insufficient clinical data. Rather, the FDA’s complete response letter was prompted by manufacturing site defects, in addition to an inability to inspect some sites in Russia and Ukraine. The filing, for a combination of camrelizumab and the VEGFR-2 inhibitor rivoceranib/apatinib in first-line liver cancer, was backed by the phase 3 Cares-301 trial, and one concern was that neither molecule is US-approved as monotherapy, and the study had no way of showing contribution of components, with the combo simply being compared against Nexavar. Not that the more benign reason behind the CRL was much solace to HLB, whose US subsidiary Elevar Therapeutics licensed the combo from HengRui last October, and whose shares plummeted 30% on the South Korean stock exchange today. The CRL came after US knockbacks for three other China-originated anti-PD-(L)1 MAbs, though Coherus’s Loqtorzi and BeiGene’s Tevimbra have now been approved after long delays.


The US fate of China-originated anti-PD-(L)1 MAbs

ProductCompanyIndicationFiled in USOutcome
Loqtorzi (toripalimab)Coherus/ Shanghai Junshi1st-line nasopharyngeal carcinoma (chemo combo), Jupiter-02 trialNov 2021 (Apr 2022 PDUFA)May 2022 CRL; new PDUFA Dec 2022 missed because of Covid travel restrictions in China; approved Oct 2023
2nd-line nasopharyngeal carcinoma (monotherapy), Polaris-02 trial
Tevimbra (tislelizumab)BeiGene (formerly licensed to Novartis)2nd-line oesophageal squamous cell carcinoma (monotherapy), Rationale-302 trialSep 2021 (Jul 2022 PDUFA)PDUFA missed because of Covid travel restrtictions in China; approved Mar 2024
1st-line oesophageal squamous cell carcinoma (chemo combo), Rationale-306 trialSep 2023 (Jul 2024 PDUFA)TBD
1st-line gastric/GEJ adenocarcinoma (chemo combo), Rationale-305 trialFeb 2024 (Dec 2024 PDUFA)TBD
CamrelizumabJiangsu HengRui/ Elevar (HLB)1st-line liver cancer (rivoceranib combo), Cares-301 trialJul 2023 (May 2024 PDUFA)May 2024 CRL because of manufacturing problems & travel restrictions in Russia/Ukraine
PenpulimabAkeso/ Sino3rd-line nasopharyngeal carcinoma (monotherapy)May 2021 (Nov 2022 PDUFA)PDUFA missed because of Covid travel restrictions in China; US development deprioritised
SintilimabInnovent (formerly licensed to Lilly)1st-line non-squam NSCLC (Alimta combo), Orient-11 trialMay 2021 (Mar 2022 PDUFA)Mar CRL after Feb 2022 adcom vote against approval; US development deprioritised
SugemalimabCStone (formerly licensed to EQRX)1st-line NSCLC, Gemstone-301 & 302 trialsNoUS development deprioritised after sintilimab CRL

Source: OncologyPipeline.