Bayer has secured FDA approval for its oral HER2 inhibitor, Hyrnuo (sevabertinib), as a first-line treatment for advanced HER2-mutant non-small cell lung cancer (NSCLC). This regulatory move comes just one year after the drug was cleared for use as a second-line option, marking a significant shift in how this specific subtype of lung cancer is managed.
The decision rests on interim data from the ongoing phase 1/2 SOHO-01 trial. The results showed an objective response rate of 75%. Specifically, 6% of patients achieved complete responses, while partial responses were observed in nearly 70% of patients with HER2-positive non-squamous NSCLC.
Competing for the Frontline Spot
This expanded label places Bayer’s drug on equal footing with Boehringer Ingelheim’s rival, Hernexeos (zongertinib). The latter was approved as a second-line option last year and moved into the frontline setting in February. That shift followed a double-quick review under the FDA’s national priority voucher programme, based on the Beamion LUNG-1 study.
While both drugs demonstrate similar efficacy in their supporting trials, the safety profiles tell a different story. Data suggests Hernexeos may have a competitive edge due to lower general toxicity. In particular, it shows a lower rate of severe diarrhoea. For patients, this could translate to better adherence and improved quality of life during treatment.
Analysts at GlobalData predict that sales for both agents will remain modest in the coming years. They estimate Hernexeos will generate around $54 million across seven major markets—including the US, UK, France, Germany, Italy, Japan, and Spain—by 2032. Hyrnuo is projected to trail slightly, reaching $49 million in the same period.
Confirmatory Trials and Patient Demographics
Both pharmaceutical companies are currently running confirmatory trials to convert their accelerated approvals into full approvals. Bayer is conducting the SOHO-02 trial, while Boehringer is executing the Beamion LUNG-2 study. Additionally, Boehringer is exploring Hernexeos as adjuvant monotherapy for early-stage HER2+ NSCLC in the Beamion LUNG-3 trial. Bayer’s panSOHO study focuses on advanced, non-NSCLC solid tumours that express HER2.
HER2 mutations occur in 2% to 4% of NSCLC cases. These mutations are linked to poor prognosis and a higher likelihood of the cancer spreading to the brain. Patients with this specific mutation are predominantly women, tend to be younger, and are usually non-smokers. Bayer estimates that up to 84,000 people are diagnosed with HER2-positive NSCLC globally each year.
From a strategic standpoint, the race to the frontline is less about raw efficacy and more about tolerability. When two drugs offer similar tumor shrinkage, the one patients can actually tolerate without severe side effects often wins in the long run. This dynamic could shape prescribing habits even if sales figures remain modest for the next decade.
Christine Roth, Bayer’s head of global product strategy and commercialisation, highlighted the clinical need behind the approval. “Lung cancer remains the leading cause of cancer-related deaths worldwide, and for patients with HER2-mutated NSCLC, a distinct subtype that often affects people who have never smoked, there remains a critical need for additional treatment options,” she said. She added that the approval highlights the potential of precision medicine to transform outcomes by matching the right patients to the right therapy at the right time.
