FDA Approves Bayer’s HYRNUO® (sevabertinib) for HER2-Mutated NSCLC

November 20, 2025 — Leads & Copy — The U.S. Food and Drug Administration (FDA) has approved Bayer’s HYRNUO® (sevabertinib) for treating 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-approved test, and who have received prior systemic therapy.

HYRNUO® is an oral, reversible, tyrosine kinase inhibitor (TKI). The FDA granted accelerated approval based on objective response rate (ORR) and duration of response (DoR). Continued approval may depend on verification and description of clinical benefit in a confirmatory trial.

The FDA’s approval was based on results from the ongoing Phase I/II SOHO-01 trial.

In 2024, the FDA granted HYRNUO® Breakthrough Therapy designation for treating adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, and who have received prior systemic therapy.

HYRNUO® is derived from Bayer’s strategic research alliance with the Broad Institute of MIT and Harvard.

HYRNUO® can cause severe diarrhea, potentially leading 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 the 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, patients should start antidiarrheal treatment and increase fluid and electrolyte intake. Dosage may need to be interrupted, reduced, or permanently discontinued based on severity.

HYRNUO® can also cause severe hepatotoxicity, characterized by elevations in liver function tests. Based on adverse reaction data, hepatotoxicity occurred in 24% of patients, including 3% Grade 3. Based on laboratory data, 35% of patients experienced increased alanine aminotransferase (ALT), including 2.3% Grade 3. Increased aspartate aminotransferase (AST) occurred in 35% of patients, including 2.3% Grade 3. Increased bilirubin occurred in 12% of patients. The median time to the first onset of AST or ALT elevation was 1.4 months (range 0.2 to 14.5). HYRNUO® was interrupted for hepatotoxicity in 4.1% of patients, the dose was reduced in 4.1%, and permanently discontinued in 0.4%. Liver function tests should be monitored at baseline, every two weeks for the first month, and then monthly, with more frequent testing for patients who develop transaminase elevations.

Interstitial lung disease (ILD)/pneumonitis can also occur. In the pooled safety population, ILD/pneumonitis occurred in two patients (0.7%), including 0.4% Grade 3. One patient required interruption of HYRNUO®. Monitor patients for new or worsening symptoms. Discontinue HYRNUO® upon confirmation of ILD/pneumonitis.

Ocular toxicity can also occur. In the pooled safety population, ocular toxicity occurred in 14% of patients, including 11% Grade 1, 2.6% Grade 2, and 0.4% Grade 3. Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist.

HYRNUO® can cause elevations of amylase and lipase levels. In the pooled safety population, increased amylase occurred in 32% of patients, including 3.2% Grade 3 or 4. Increased lipase elevation occurred in 40% of patients, including 10% Grade 3 or 4. Monitor amylase and lipase regularly during treatment. Dosage adjustments may be needed.

HYRNUO® can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use effective contraception during treatment and for one week after the last dose. Male patients with female partners of reproductive potential should use effective contraception during treatment and for one week after the last dose.

In SOHO-01 (Groups D and E), serious adverse reactions occurred in 31% of patients. The most common adverse reactions (>20%) were diarrhea (87%), rash (66%), paronychia (33%), stomatitis (29%), and nausea (21%).

Concomitant use with CYP3A inhibitors or inducers, and with P-gp or CYP1A1 substrates, may require dosage adjustments and monitoring.

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes seven marketed products across diverse indications and multiple compounds in different stages of clinical development.

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In fiscal 2024, the Group employed around 93,000 people and had sales of 46.6 billion euros.

More information can be found at www.pharma.bayer.com

References: