Key Takeaways:
The U.S. Food and Drug Administration granted accelerated approval to sevabertinib (HYRNUO) for first-line treatment of adults with locally advanced or metastatic non-squamous non-small cell lung cancer whose tumors carry HER2 (ERBB2) tyrosine kinase domain activating mutations, Bayer said Sept. 9.
"The FDA's accelerated approval of HYRNUO marks an important advance for treatment-naïve patients with HER2-mutated NSCLC," said Xiuning Le, MD, PhD, associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center and lead investigator of the SOHO-01 trial. "This milestone also underscores the critical importance of comprehensive molecular testing at diagnosis, including for activating HER2 mutations, to ensure patients receive the most appropriate treatment as early as possible."
The decision rests on Cohort F of the ongoing Phase I/II SOHO-01 trial (NCT05099172), which enrolled 69 treatment-naïve patients. Confirmed objective response rate was 75% (95% CI: 64, 85), including complete responses in 6% of patients (n=4) and partial responses in 70% (n=48). Among responders, 73% held their response for at least six months and 38% for at least 12 months. The recommended dose is 20 mg orally twice daily with food, continued until disease progression or unacceptable toxicity.
Continued approval depends on verification of clinical benefit in the Phase III SOHO-02 confirmatory trial (NCT06452277), which compares sevabertinib against standard of care in the same treatment-naïve population. Bayer did not disclose a completion date for that study. The FDA reviewed the application under Project Orbis in collaboration with the U.K.'s Medicines and Healthcare Products Regulatory Agency, with reviews at other participating agencies still ongoing.
The approval extends a label Bayer first secured in November 2025 for previously treated patients with the same HER2 TKD activating mutations. Activating HER2 mutations appear in 2% to 4% of advanced NSCLC cases, a subtype that disproportionately affects people who have never smoked, according to the company. Lung cancer remains the leading cause of cancer-related deaths worldwide.
Safety data from the pooled population of 191 patients who received sevabertinib showed diarrhea in 89%, including 16% Grade 3, with a median time to first onset of four days. Hepatotoxicity occurred in 29% of patients, including 3.1% Grade 3 and 0.3% Grade 4. Serious adverse reactions occurred in 33% of patients in SOHO-01, most commonly diarrhea (3.7%), vomiting (3.7%), dyspnea (3.1%), pneumonia (2.6%) and pleural effusion (2.1%). One fatal adverse reaction of cerebral infarction occurred in a single patient (0.5%).
The label also carries warnings for interstitial lung disease/pneumonitis, which occurred in four patients (1.4%), left ventricular dysfunction, ocular toxicity in 17% of patients, and pancreatic enzyme elevation, with lipase increases in 48% of patients including 13% Grade 3. Sevabertinib is a CYP3A substrate and a weak-to-moderate CYP3A inhibitor, so concomitant use with strong CYP3A inhibitors or inducers should be avoided.
Eligibility is narrow. The indication covers only HER2 TKD activating mutations confirmed by an FDA-authorized test, and does not extend to HER2 protein overexpression or gene amplification, which are distinct biomarkers. That distinction puts molecular profiling at diagnosis ahead of treatment selection, a workflow change that moves specialty pharmacists and pathologists earlier into the care pathway.
Bayer reported fiscal 2025 group sales of 45.6 billion euros and R&D expenses of 5.8 billion euros, with roughly 88,000 employees. The company did not disclose a U.S. list price for HYRNUO or a peak sales estimate for the first-line indication. Bayer's oncology franchise spans marketed products in prostate cancer and an approved TRK inhibitor for NTRK fusion-positive tumors, alongside targeted radionuclide and immuno-oncology programs in development.
The commercial read hinges on how quickly SOHO-02 reads out and whether it confirms the response data. A failed confirmatory trial would expose the first-line label to withdrawal or narrowing, the same regulatory mechanism the FDA used in September 2026 when it withdrew the Krazati/Erbitux approval in KRAS G12C-mutated colorectal cancer. Investors will watch for SOHO-02 enrollment milestones and any update to Bayer's oncology revenue guidance.
This article is for informational purposes only and does not constitute investment advice.
