Bayer announced receipt of US FDA Priority Review for a supplemental New Drug Application (sNDA) for Hyrnuo (sevabertinib), an oral reversible HER2/EGFR tyrosine kinase inhibitor (TKI). The German giant is aiming to expand Hyrnuo’s indications to include first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations and who have received no prior systemic therapy. The filing is supported by preliminary data from Cohort F of the ongoing Phase I/II SOHO-01 trial (NCT05099172).
Priority Review compresses the standard FDA review timeline from 10-12 months to 6 months and is reserved for therapies that, if approved, would offer a meaningful improvement in safety or effectiveness for a serious condition. Hyrnuo received US FDA accelerated approval in November 2025 for a distinct, previously treated population — adults with locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD activating mutations after prior systemic therapy — based on objective response rate (ORR) and duration of response (DOR). That earlier indication remains subject to confirmatory trial requirements. The current sNDA represents a line extension into the first-line setting, where Hyrnuo is not yet approved.
Sevabertinib inhibits mutated HER2, including exon 20 insertions and point mutations, as well as EGFR, with selectivity for mutant over wild-type EGFR. The molecule was developed through Bayer’s research alliance with the Broad Institute of MIT and Harvard.
The clinical case for the first-line sNDA rests on Cohort F of SOHO-01, which enrolled 73 treatment-naïve patients with locally advanced or metastatic HER2-mutated NSCLC. According to data published in the New England Journal of Medicine in July 2025, with a data cutoff of June 27, 2025, the confirmed ORR by blinded independent central review per RECIST v1.1 was 71% (95% CI: 59–81%). Median duration of response was 11.0 months (95% CI: 8.1–not estimable), and median progression-free survival had not been reached at the time of analysis, with a median follow-up of 9.9 months. Among patients with brain metastases, the ORR was 78%. Grade 3 or higher drug-related adverse events occurred in 21% of patients, with any-grade drug-related adverse events reported in 97%. These figures were not disclosed in the current Priority Review announcement but were reported in the NEJM publication and concurrent ESMO 2025 presentations from the same data cut.
The safety profile of sevabertinib across the broader SOHO-01 pooled population includes diarrhea in 86% of patients (Grade 3 in 15%), hepatotoxicity in 24%, and ocular toxicity in 14%. Pancreatic enzyme elevations — increased lipase in 40% and increased amylase in 32% — were also observed, with Grade 3 or 4 events in 10% and 3.2% of patients, respectively. Interstitial lung disease or pneumonitis occurred in 0.7% of the pooled safety population.