U.S. FDA Grants Priority Review to Supplemental New Drug Application for HYRNUO® (sevabertinib) Under Investigation as a First-Line Treatment of HER2-Mutated Non-Small Cell Lung Cancer
Bayer announced that the U.S. Food and Drug Administration (FDA) has granted HYRNUO® (sevabertinib) Priority Review status for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations in patients with no prior therapy. HYRNUO is not currently approved in this first-line setting.
In November 2025, HYRNUO received U.S. FDA accelerated approval for patients with locally advanced or metastatic NSCLC whose tumors have HER2 TKD activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.2 This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.2
“The U.S. FDA’s decision to grant Priority Review for HYRNUO is an important milestone as we continue to study this investigational treatment option in HER2-mutated non-small cell lung cancer,” said Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division. “We look forward to working closely with regulatory authorities as they review the data supporting this application for use in the first-line setting.”
“There continues to be progress in understanding and treating HER2-mutated NSCLC, and Bayer is committed to further investigating the full potential of HYRNUO as a treatment option,” said Nelson Ambrogio, President, Bayer U.S. Pharmaceuticals. “We appreciate the FDA’s Priority Review designation and remain focused on working through the regulatory process to help address the needs of this patient population.”
The regulatory application for first-line use of HYRNUO is based on preliminary clinical evidence from Cohort F (patients who had not previously received treatment) of the ongoing Phase I/II SOHO-01 Study (NCT05099172) evaluating the efficacy and safety of HYRNUO in patients with locally advanced or metastatic HER2-mutated NSCLC.2
About HYRNUO
HYRNUO is an oral, reversible, small molecule, tyrosine kinase inhibitor (TKI) that inhibits mutated human HER2, including HER2 exon 20 insertions and HER2 point mutations, as well as epidermal growth factor receptors (EGFR), with selectivity for mutated vs wild-type EGFR. HYRNUO works by blocking certain enzymes called tyrosine kinases, which are involved in the growth of cancer cells. HYRNUO is derived from Bayer’s strategic research alliance with the Broad Institute of MIT and Harvard in Cambridge, MA, USA.
About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer-related deaths worldwide.3 NSCLC is the most common type of lung cancer, accounting for more than 85% of cases.4 Activating HER2 mutations are found in 2% to 4% of patients with advanced NSCLC.5 80% of people diagnosed with NSCLC have already progressed to advanced stages, which makes it difficult to treat.6
INDICATION
HYRNUO is indicated for the treatment of patients with locally advanced or metastatic non-squamous NSCLC whose tumors have HER2 TKD activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. HYRNUO is not currently approved in this first-line setting.2
This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
IMPORTANT SAFETY INFORMATION
Warnings & Precautions
Diarrhea
HYRNUO can cause severe diarrhea that can lead to dehydration and electrolyte imbalances.
In the pooled safety population, diarrhea was reported in 86% of patients who received HYRNUO including Grade 3 in 15%. The median time to first onset of any grade diarrhea was four days. Dosage interruptions occurred in 15% of patients, and dose reductions occurred in 12% of patients.
At the first sign of diarrhea or increased bowel movement frequency, instruct patients to start an antidiarrheal treatment (e.g., loperamide), and to increase their fluid and electrolyte intake. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity.
Hepatotoxicity
HYRNUO can cause severe hepatotoxicity characterized by elevations of liver function tests.
In the pooled safety population, based on adverse reaction data, hepatotoxicity occurred in 24% of patients treated with HYRNUO including 3% Grade 3. Based on laboratory data, 35% of patients treated with HYRNUO experienced increased alanine aminotransferase (ALT), including 2.3% Grade 3. Increased aspartate aminotransferase (AST) occurred in 35% of patients treated with HYRNUO, including 2.3% Grade 3. Increased bilirubin occurred in 12% of patients treated with HYRNUO. The median time to first onset of AST or ALT elevation was 1.4 (range 0.2 to 14.5) months. HYRNUO was interrupted for an adverse reaction of hepatotoxicity in 4.1% of patients, the dose was reduced in 4.1% and permanently discontinued in 0.4%.
Monitor liver function tests including ALT, AST, and total bilirubin at baseline prior to the first administration of HYRNUO, every 2 weeks for the first month and then monthly thereafter as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Interrupt, reduce the dose or permanently discontinue HYRNUO based on the severity of the adverse reaction.
Interstitial Lung Disease/Pneumonitis
HYRNUO can cause severe interstitial lung disease (ILD)/pneumonitis. In the pooled safety population, ILD/pneumonitis occurred in two patients (0.7%) treated with HYRNUO, including 0.4% Grade 3. One patient required interruption of HYRNUO.
Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Discontinue HYRNUO upon confirmation of ILD/pneumonitis.
Ocular Toxicity
HYRNUO can cause ocular toxicity.
In the pooled safety population, ocular toxicity occurred in 14% of patients treated with HYRNUO, including 11% Grade 1, 2.6% Grade 2 and 0.4% Grade 3 (one case of corneal epithelial microcysts with temporary unilateral blindness).
Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity.
Pancreatic Enzyme Elevation
HYRNUO can cause elevations of amylase and lipase levels. In the pooled safety population, based on laboratory data, increased amylase occurred in 32% of patients treated with HYRNUO, including 3.2% Grade 3 or 4. Increased lipase elevation occurred in 40% of patients treated with HYRNUO, including 10% Grade 3 or 4. Two patients (0.7%) required interruption of HYRNUO due to increased lipase and three (1.1%) required interruption of HYRNUO due to increased amylase. The median time to onset of increased amylase/lipase was 1.4 months (range: 0.2 to 17 months).
Monitor amylase and lipase regularly during treatment with HYRNUO. Interrupt, reduce the dose or permanently discontinue HYRNUO based on severity.
Embryo-fetal toxicity
Based on findings from animal studies and its mechanism of action, HYRNUO can cause fetal harm when administered to a pregnant woman. In embryo-fetal development studies, oral administration of sevabertinib to pregnant rats during the period of organogenesis resulted in alterations to growth at maternal exposures ≥0.18 times the human exposure based on area under the curve (AUC) at the clinical dose of 20 mg twice daily. Animal studies with disrupted or depleted HER2/EGFR and in vitro assays have demonstrated that inhibition of HER2 and/or EGFR results in structural abnormalities, alteration to growth, and embryo-fetal and infant mortality.
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with HYRNUO and for 1 week after the last dose.
About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The company has the passion and determination to develop new medicines that help improve and extend the lives of people living with cancer. The oncology franchise at Bayer includes several marketed products across diverse indications and multiple compounds in different stages of clinical development. We have a wealth of expertise in areas including:
Tumor Intrinsic Pathways, Targeted Radionuclide Therapies, and Next-Generation Immuno-Oncology. We are advancing prostate cancer treatment from early to metastatic stage, with the goal of extending survival while limiting side effects. Part of Bayer’s focus on innovative precision oncology treatments, includes an approved TRK inhibitor exclusively designed to treat tumors that have an NTRK gene fusion, the oncogenic driver of tumor growth and spread.
About Bayer
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses.
At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2025, the Group employed around 88,000 people and had sales of 45.6 billion euros. R&D expenses amounted to 5.8 billion euros.
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