Lung cancer driven by mutated HER2 proteins already has a targeted therapy, the blockbuster product Enhertu from AstraZeneca and Daiichi Sankyo. A Boehringer Ingelheim drug has won FDA approval for the same indication, giving patients a drug choice with easier dosing as well as data indicating better safety and tolerability.
The late Friday approval of the Boehringer-Ingelheim drug, zongertinib, covers the treatment of adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC). In addition to having tumors with mutations to HER2, also called ERBB2, patients eligible for treatment must have received at least one prior systemic therapy. Boehringer’s new lung cancer drug, a once-daily tablet, will be marketed under the brand name Hernexeos. The FDA also approved a Thermos Fisher Scientific companion diagnostic that identifies the HER2 mutation making patients eligible for Hernexeos.
NSCLC is the most common type of lung cancer. HER2 is a protein that plays a role in the growth and division of cells. It’s abundant in some types of cancer and when mutated, can drive cancer growth and spread. These mutations are rare, occurring in about 2% to 4% of cases of NSCLC, according to Ingelheim, Germany-based Boehringer. Lung cancers driven by HER2 mutations are associated with poor prognosis and a higher incidence of brain metastases.
RCM Outsourcing: Balancing Human Expertise & Smart Technology
Greenway Health blends smart technology with human expertise to elevate revenue cycle.
Hernexeos is an oral small molecule designed to inhibit HER2. The drug belongs to the class of drugs called tyrosine kinase inhibitors (TKIs). FDA approval of the drug was based on data from an open-label Phase 1b study in two parts: the first evaluated patients with advanced solid tumors with changes to the HER2 gene while the second part specifically focused on patients with HER2-mutated NSCLC. In the lung cancer portion, results showed a 75% objective response rate; 69% of patients had a partial response and a duration of response of six months or greater was observed in 58% of patients.
The most common adverse event reported in the test of Hernexeos was diarrhea. Liver complications were also observed in the study and the Hernexeos label warns clinicians to monitor for signs of such problems, including drug-induced liver injury. Full data from the study were presented in April during the annual meeting of the American Association for Cancer Research in April and published in The New England Journal of Medicine.
In Boehringer’s announcement of Hernexeos’s approval, Dr. John Heymach, chair of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center and an investigator in the drug’s studies, noted the durable response to the drug as well as its manageable safety profile.
“In a patient population where there are currently limited treatment options, this approval represents a significant advancement in cancer care,” Heymach said.
5 High-Impact Tax Strategies Every Physician Should Use in 2026 to Reduce Their Tax Bill
AI-native tax firm Gelt combines top human tax experts with AI to help physicians and healthcare practices use data-driven tax strategies to lower liabilities, improve profitability, and future-proof their finances.
The safety precautions identified on the Hernexeos label are not listed in a black box warning, which is reserved for serious and potentially life-threatening complications. The label of AstraZeneca and Daiichi Sankyo drug Enhertu carries a black box warning for the risk of interstitial lung disease. Enhertu belongs to the class of targeted therapies called antibody drug conjugates (ADCs). The risks vary from one ADC to another but many products in this class carry boxed warnings on their labels. These drugs are also administered as intravenous infusions, which poses a higher dosing burden to patients compared to oral small molecules.
Enhertu, which was initially approved for treating HER2-positive breast cancers, added NSCLC to its label in 2022. AstraZeneca and Daiichi Sankyo share in the commercialization of this ADC, which accounted for more than $3.7 billion in revenue across all of its approved indications last year.
Privately-held Boehringer isn’t the only company trying to compete with an oral small molecule aiming to offer better safety and tolerability. In May, the FDA accepted Bayer’s submission for sevabertinib as a treatment for advanced cases of HER2-mutated NSCLC that has received a prior systemic therapy. The application was accepted under priority review, which means a regulatory decision for the Bayer drug could be coming late this year.
Vicky Brown, Boehringer’s U.S. senior vice president and head of oncology, immunology & eye health, said via email that the company’s goal is to make Hernexeos available to patients as soon as they receive a prescription. The drug will be supplied in 60-tablet bottles carrying a wholesale price of $21,667.01, which Brown said reflects the drug’s potential as a treatment for patients who have had limited choices.
The regulatory decision for Hernexeos is an accelerated approval based on results from its Phase 1b test. Retaining approval is contingent on positive results from a confirmatory study. A Phase 3 study underway is evaluating Hernexeos as a first-line treatment in adults with advanced NSCLC driven by HER2 mutations. The study drug is being compared against the Merck immunotherapy Keytruda plus chemotherapy. The main goal of this open-label, 416-patient study is measuring progression-free survival. Preliminary data are expected in late 2026.
Photo: Kettel/ullstein bild, via Getty Images