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
Product | Company | Indication | Filed in US | Outcome |
---|---|---|---|---|
Loqtorzi (toripalimab) | Coherus/ Shanghai Junshi | 1st-line nasopharyngeal carcinoma (chemo combo), Jupiter-02 trial | Nov 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 trial | Sep 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 trial | Sep 2023 (Jul 2024 PDUFA) | TBD | ||
1st-line gastric/GEJ adenocarcinoma (chemo combo), Rationale-305 trial | Feb 2024 (Dec 2024 PDUFA) | TBD | ||
Camrelizumab | Jiangsu HengRui/ Elevar (HLB) | 1st-line liver cancer (rivoceranib combo), Cares-301 trial | Jul 2023 (May 2024 PDUFA) | May 2024 CRL because of manufacturing problems & travel restrictions in Russia/Ukraine |
Penpulimab | Akeso/ Sino | 3rd-line nasopharyngeal carcinoma (monotherapy) | May 2021 (Nov 2022 PDUFA) | PDUFA missed because of Covid travel restrictions in China; US development deprioritised |
Sintilimab | Innovent (formerly licensed to Lilly) | 1st-line non-squam NSCLC (Alimta combo), Orient-11 trial | May 2021 (Mar 2022 PDUFA) | Mar CRL after Feb 2022 adcom vote against approval; US development deprioritised |
Sugemalimab | CStone (formerly licensed to EQRX) | 1st-line NSCLC, Gemstone-301 & 302 trials | No | US development deprioritised after sintilimab CRL |
Source: OncologyPipeline.
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