
Merkel cell provides Incyte’s laggard a way in
A few years ago the first approval of an anti-PD-(L)1 drug would have been trumpeted far and wide. But with seven already on the US market Incyte did not even disclose that it had filed the Macrogenics-originated retifanlimab, and the announcement yesterday that the drug had been approved as Zynyz for Merkel cell carcinoma thus came as a surprise. Investors received it with a shrug, presumably because Merkel cell is such an insignificant use. Still, this is not the point; Incyte needed retifanlimab to be approved not so it could have a monotherapy challenger but to give it an in-house PD-1 backbone for future combinations. The key lesson for laggards pursuing similar strategies is that Merkel cell – where only Merck & Co’s Keytruda and Merck KGaA/Pfizer’s Bavencio are approved, both through the accelerated pathway – remains a viable niche indication in which a quick nod is possible. Incyte had tried and failed to get retifanlimab greenlit in another peripheral use, squamous cell carcinoma of the anal canal, but a US adcom slammed its data in 2021, and a complete response letter followed.
Anti-PD-(L)1 laggards in the US | |||
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Project | Company | Lead indication(s) | US status |
Toripalimab | Coherus/ Shanghai Junshi | 1st-line chemo combo & 3rd-line monoRx nasopharyngeal carcinoma | 2 May 2022 CRL; new Pdufa date 23 Dec 2022 missed because of Covid travel restrictions |
Tislelizumab | Novartis/ Beigene | 2nd-line oesophageal squamous cell carcinoma | 12 Jul 2022 Pdufa date missed because of Covid travel restrictions |
Penpulimab | Akeso/ Sino | 3rd-line nasopharyngeal carcinoma | 2022 Pdufa date missed, presumably because of Covid travel restrictions |
Cosibelimab* | Checkpoint (Fortress) | Cutaneous squamous cell carcinoma | 4 Jan 2024 Pdufa date, no adcom |
Envafolimab* | Tracon/ Alphamab/ 3D Medicines | 1st-line biliary tract cancer (gemcitabine combo) | Ph3 ends Jan 2024 (delayed from Dec 2021) |
Serplulimab | Shanghai Henlius/ Fosun | 1st-line SCLC, vs Tecentriq | Ph3 ends Jun 2024 |
Zimberelimab | Arcus (via Wuxi/ Gloriabio) | 1st-line PD-L1+ve NSCLC (+/- domvanalimab) | Ph3 trial ends Feb 2024 (earlier Dec 2025) |
Sasanlimab | Pfizer | Non-muscle-invasive bladder cancer (BCG combo) | Ph3 ends Jun 2025 (delayed from Jun 2024) |
Cetrelimab (JNJ-63723283) | Johnson & Johnson | Muscle-invasive bladder cancer (TAR-200 combo) | Ph3 trial ends Dec 2026 |
Ezabenlimab (BI 754091) | Boehringer Ingelheim | Various, Lag3 & VEGF/Ang2 combos | Ph2 trial ends May 2024 |
Balstilimab | Agenus | 2nd-line cervical cancer | Filing pulled 22 Oct 2021 |
Sintilimab | Innovent | 1st-line non-squam NSCLC (Alimta combo) | 24 Mar 2022 CRL |
Sugemalimab* | Cstone/ EQRX | 1st-line NSCLC | US filing plan abandoned |
Spartalizumab | Novartis | Melanoma (Tafinlar+Mekinist combo) | Failed Combi-I trial Aug 2020 (deprioritised) |
Note: *anti-PD-L1; all others are anti-PD-1. Source: company disclosures & clinicaltrials.gov. |