Otsuka and Cullinan chase Dizal

Zipalertinib, an EGFR exon 20 inhibitor originated by Otsuka's Taiho subsidiary, licensed to Cullinan and then bought back by Otsuka, is headed to the FDA. The move, a shot at an accelerated approval, comes after zipalertinib met the primary ORR endpoint of its phase 1/2 Rezilient-1 study in relapsed NSCLC patients with EGFR exon 20 insertion mutations. Cullinan said zipalertinib would be filed in the second half of this year, and its shares rose 8% on Wednesday. However, the project lags Dizal's similarly acting sunvozertinib, which was filed with priority review this month, and faces a possible July FDA action date. One question is whether either zipalertinib or sunvozertinib can receive accelerated approval given that Johnson & Johnson's Rybrevant is fully approved in second-line EGFR exon 20 NSCLC. However, Rybrevant's nod is in post-chemo patients (it also has a first-line label as part of a chemo combo), and both Rezilient-1 and sunvozertinib's supporting WU-Kong1 study included some patients who had progressed on Rybrevant as well as chemo. Cullinan licensed ex-Japan zipalertinib rights in 2019, but in 2022 Otsuka bought these back, with Cullinan retaining a US profit share. A potentially confirmatory phase 3 trial, Rezilient-3, started in 2023.

A battle in second-line EGFR exon 20 insertion NSCLC

Note: *anti-EGFR x cMet MAb; the rest are small-molecule EGFR inhibitors. Source: OncologyPipeline.