U.S. FDA Grants Accelerated Approval to Bayer’s HYRNUO® (sevabertinib) as a First-Line Targeted Therapy for Patients with HER2-Mutated Non-Small Cell Lung Cancer

Bayer announced today that following Priority Review and Breakthrough Therapy Designation, the U.S. Food and Drug Administration (FDA) has granted accelerated approval for HYRNUO^® (sevabertinib), for the first-line treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have human epidermal growth factor receptor 2 (HER2/ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.¹ HYRNUO is an oral, reversible, small molecule, tyrosine kinase inhibitor (TKI).

The FDA approved this indication for HYRNUO under accelerated approval based on objective response rate (ORR) and duration of response (DOR) demonstrated in treatment-naïve patients (N=69, Cohort F) in the ongoing Phase I/II SOHO-01 trial (NCT05099172).¹ The trial is evaluating the efficacy and safety in patients with locally advanced or metastatic non-squamous HER2-mutated NSCLC.¹ In this cohort, the ORR was 75% (95% CI: 64, 85; N=69) including complete responses in 6% (n=4) of patients and partial responses in 70% (n=48) of patients, with 73% of responders maintaining response for at least six months and 38% maintaining response for at least 12 months.¹ Continued approval for this indication may be contingent upon verification and description of clinical benefit in the ongoing Phase III SOHO-02 confirmatory trial (NCT06452277), which is evaluating HYRNUO versus standard of care in treatment-naïve patients with advanced HER2-mutated NSCLC.

The safety profile of HYRNUO was consistent with previous findings. In the SOHO-01 study, the most common adverse reactions (>20%) in patients who received HYRNUO (N=191) were diarrhea, rash, stomatitis, paronychia, nausea and weight decreased. Please see Important Safety Information below for additional details.

“The FDA’s accelerated approval of HYRNUO marks an important advance for treatment-naïve patients with HER2-mutated NSCLC,” said SOHO-01 lead investigator, Xiuning Le, MD, PhD, associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, Texas. “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.”

“Today’s FDA approval of HYRNUO as an initial treatment option for locally advanced or metastatic non-squamous HER2-mutated NSCLC is an important milestone for patients and a powerful validation of Bayer’s commitment to advancing precision oncology in areas with the highest unmet needs,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer. “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.² This approval underscores the potential of precision medicine to transform outcomes by matching the right patients to the right therapy at the right time.”

“Today’s accelerated approval of HYRNUO in the first-line setting marks an important milestone for patients with HER2-mutated locally advanced or metastatic non-squamous NSCLC,” said Nelson Ambrogio, President, Bayer U.S. Pharmaceuticals and Member of the Pharmaceuticals Leadership Team at Bayer. “We are pleased to expand access to this targeted treatment option earlier in the disease journey and continue delivering meaningful innovations to patients with difficult-to-treat cancers.”

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 received prior systemic therapy.³ This indication is approved under accelerated approval based on ORR and DOR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

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.² 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 a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.

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 89% of patients who received HYRNUO including 16% Grade 3. 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 14% 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 29% of patients treated with HYRNUO, including 3.1% Grade 3 and 0.3% Grade 4.

Based on laboratory data, 41% of patients treated with HYRNUO experienced increased alanine aminotransferase (ALT), including 2.5% Grade 3 and 0.4% Grade 4. Increased aspartate aminotransferase (AST) occurred in 44% of patients treated with HYRNUO, including 2.5% Grade 3. Increased bilirubin occurred in 15% of patients treated with HYRNUO. The median time to first onset of AST or ALT elevation was 1.4 (range: 0.2 to 24.1) months.

HYRNUO was interrupted for an adverse reaction of hepatotoxicity in 4.2% of patients, the dose was reduced in 4.9%, and permanently discontinued in 0.3%.

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 severity.

Interstitial Lung Disease/Pneumonitis

HYRNUO can cause severe interstitial lung disease (ILD)/pneumonitis.

In the pooled safety population, ILD/pneumonitis occurred in four patients (1.4%) treated with HYRNUO, including 0.3% 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.

Left Ventricular Dysfunction

HYRNUO can cause severe left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has occurred with anti-HER2 therapies, including HYRNUO.

Treatment with HYRNUO has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment. In the pooled safety population, LVEF decrease occurred in one patient (0.3%) treated with HYRNUO. This Grade 3 LVEF decrease required permanent discontinuation of HYRNUO, and the event recovered.

Evaluate LVEF prior to initiation of HYRNUO and monitor at regular intervals during treatment and as clinically indicated. Interrupt, reduce the dose, or permanently discontinue HYRNUO based on severity.

Ocular Toxicity

HYRNUO can cause ocular toxicity.

In the pooled safety population, ocular toxicity occurred in 17% of patients treated with HYRNUO, including 11% Grade 1, 4.9% Grade 2, and 0.3% 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 39% of patients treated with HYRNUO, including 3.9% Grade 3 and 0.7% Grade 4. Increased lipase occurred in 48% of patients treated with HYRNUO, including 13% Grade 3 and 1.1% Grade 4. Four patients (1.4%) required interruption of HYRNUO due to increased lipase and three (1%) required interruption of HYRNUO due to increased amylase. One patient (0.3%) required dose reduction of HYRNUO due to increased amylase. The median time to onset of increased amylase/lipase was 0.7 months (range: 0.2 to 20.4 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.

Adverse Reactions

In SOHO-01, serious adverse reactions occurred in 33% of patients who received HYRNUO. Serious adverse reactions in ≥2% of patients were diarrhea (3.7%), dyspnea (3.1%), vomiting (3.7%), pneumonia (2.6%), and pleural effusion (2.1%). A fatal adverse reaction of cerebral infarction occurred in one patient (0.5%) who received HYRNUO.

The most common adverse reactions (>20%) in patients who received HYRNUO were diarrhea (90%), rash (76%), stomatitis (37%), paronychia (36%), nausea (22%) and weight decreased (22%).

The most common (≥2%) Grade 3 or 4 laboratory abnormalities were lipase increased (18%), potassium decreased (18%), phosphate decreased (13%), lymphocyte count decreased (4.6%), sodium decreased (5%), amylase increased (5%), hemoglobin decreased (3.7%), ALT increased (3.2%), and increased AST (2.6%). Laboratory abnormalities in <20% of patients who received HYRNUO include bilirubin increased (19%; all were Grades 1 and 2), platelet count decreased, and neutrophil count decreased (16% each).

Clinically relevant adverse reactions in <15% of patients who received HYRNUO included abdominal pain (14%), cardiac arrhythmia (10%; including arrhythmia, atrial fibrillation, atrial tachycardia, atrioventricular block complete, atrioventricular block first degree, electrocardiogram QT prolonged, sinus arrhythmia, sinus bradycardia, sinus tachycardia, supraventricular extrasystoles, supraventricular tachycardia, tachycardia, and ventricular extrasystoles), and alopecia (7%).

Drug Interactions

Effects of Other Drugs on HYRNUO – Sevabertinib is a CYP3A substrate. Concomitant use with a strong or moderate CYP3A inhibitor may increase sevabertinib plasma concentrations, which may increase the risk of HYRNUO-associated adverse reactions. Monitor patients for increased HYRNUO-associated adverse reactions with moderate CYP3A inhibitors. Avoid concomitant use of HYRNUO with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce HYRNUO dose.

Concomitant use with a strong or moderate CYP3A inducer may decrease sevabertinib plasma concentrations, which may decrease the effectiveness of HYRNUO. Avoid concomitant use of HYRNUO with strong or moderate CYP3A inducers.

Effects of HYRNUO on Other Drugs – Sevabertinib is a weak to moderate CYP3A inhibitor. Sevabertinib increases exposure of CYP3A substrates, which may increase the risk of adverse reactions related to these substrates. Avoid concomitant use of HYRNUO with CYP3A substrates where minimal increases in the concentration may lead to serious adverse reactions unless otherwise recommended in the Prescribing Information of the CYP3A substrate.

Sevabertinib is a P-gp inhibitor. Sevabertinib increases exposure of P-gp substrates, which may increase the risk of adverse reactions related to these substrates. Refer to the Prescribing Information for P-gp substrates where minimal increases in the concentration may lead to serious adverse reactions.

Sevabertinib is an inhibitor of CYP1A1 in vitro. Sevabertinib may increase exposure of CYP1A1 substrates, which may increase the risk of adverse reactions related to these substrates. Refer to the Prescribing Information of CYP1A1 substrates.

You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.

Please see full Prescribing Information.

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. For more information, go to www.bayer.com.

^© 2026 Bayer

BAYER and the Bayer Cross and HYRNUO are registered trademarks of Bayer.

Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

View source version on businesswire.com: https://www.businesswire.com/news/home/20260909948789/en/

Media gallery