Zongertinib

RIDGEFIELD, CT, USA and INGELHEIM, Germany I August 08, 2025 I Boehringer Ingelheim’s HERNEXEOS® (zongertinib tablets) has been approved by the U.S. Food and Drug Administration (FDA). The kinase inhibitor is indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy. 1 This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 1 “With the approval of zongertinib, we have an effective, targeted, orally administered treatment option for patients with HER2 (ERBB2)-mutant non-small cell lung cancer in the U.S. that not only elicits a durable response but, importantly, has a manageable safety profile,” said Dr. John Heymach, MD, PhD, chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, and coordinating investigator for the Beamion-LUNG 1 trial. “In a patient population where there are currently limited treatment options, this approval represents a significant advancement in cancer care.” Accelerated approval is based on data from the Phase Ib Beamion-LUNG 1 trial, demonstrating an objective response rate of 75% (N=71), 6% of patients had a complete response and 69% of patients had a partial response and a duration of response of ≥6 months in 58% of patients (n=53). 1 Positive results from the Beamion-LUNG 1 trial were previously presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 and simultaneously published in The New England Journal of Medicine . 2 Zongertinib demonstrated a manageable safety profile with a 2.9% discontinuation rate. In the pooled safety population, the most common (> 20%) adverse reactions were diarrhea (53%), hepatotoxicity (27%), rash (27%), fatigue (22%), and nausea (21%). 1 “We are grateful to be able to bring forward HERNEXEOS, which has the potential to reset the benchmark for those living with HER2-mutant advanced non-small cell lung cancer, a condition associated with a particularly poor prognosis,” said Shashank Deshpande, Chairman of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “Believing in the power of scientific innovation, we aim to provide meaningful improvements to this patient population. Recognizing its potential, we accelerated development to deliver this new treatment option to patients within four years of starting the first clinical trial.” Harnessing the power of precision medicine by targeting HER2 mutations in lung cancer HER2 (ERBB2) mutations occur in approximately 2–4% of NSCLC cases and are associated with a poor prognosis and higher incidence of brain metastases. 3,4,5 Alterations in the HER2 (ERBB2) gene, including mutations, amplification and overexpression, trigger uncontrolled cell proliferation, inhibiting cell death, and promoting tumor growth and spread. 3,5 Comprehensive biomarker testing using next generation sequencing determines a patient’s eligibility for treatment with zongertinib by identifying HER2 (ERBB2)-mutant advanced NSCLC. 1,5 “The advocacy community is thrilled about the approval of zongertinib, as it is another testament to the importance of personalized options for lung cancer that allow for a much more targeted approach for a subgroup of patients who have been waiting many years for innovative treatments,” said Marcia Horn, President and CEO, International Cancer Advocacy Network and Executive Director of the Exon 20 Group/HER2 Warriors. “Understanding your cancer’s unique biomarkers, including HER2, through comprehensive testing is critical for all patients with NSCLC, as it can unlock targeted treatment options.” About non-small cell lung cancer (NSCLC) Lung cancer claims more lives than any other cancer type and the incidence is set to increase to over 3 million cases worldwide by 2040. 5,6 NSCLC is the most common type of lung cancer. 3 Due to a lack of symptoms and misdiagnoses,7 most patients with NSCLC present at stage III or IV, where the disease has metastasized locally or to other organs. 8 The estimated 5-year survival rate historically has been less than 10% for metastatic disease. 9,10,11 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. 12,13,14 About zongertinib Zongertinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 (ERBB2). 1 This orally administered, targeted therapy was approved as HERNEXEOS® (zongertinib tablets) under the FDA’s Accelerated Approval Program, after securing Priority Review as well as Breakthrough Therapy and Fast Track Designations. 1 The treatment is being evaluated in ongoing trials, across a range of advanced solid tumors with HER2 alterations. About Boehringer Ingelheim in oncology We have a clear aspiration – to transform the lives of people with cancer by delivering meaningful advances, with the ultimate goal of curing a range of cancers. Boehringer Ingelheim’s generational commitment to driving scientific innovation is reflected by the company’s robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as the smart combination of these approaches. Boehringer’s ambition in oncology is to take a diligent and broad approach, creating a collaborative research network to tap into a diversity of minds, which is vital in addressing some of the most challenging, but potentially most impactful, areas of cancer research. Simply put, for Boehringer Ingelheim, cancer care is personal, today and for generations. Read more at Boehringer-Ingelheim.com and, Boehringer-Ingelheim.com/US . About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,500 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at Boehringer-Ingelheim.com and Boehringer-Ingelheim.com/US . The following information is intended for U.S. audiences only: About HERNEXEOS® HERNEXEOS® (zongertinib tablets) is a kinase inhibitor indicated for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy. Boehringer Ingelheim’s CareConnect4Me patient support program Boehringer’s goal is to make HERNEXEOS® (zongertinib tablets) easily accessible in the U.S. through a comprehensive patient support program, CareConnect4MeTM, that provides a broad range of access and clinical support solutions, including financial support services. For those in the U.S., visit www.HERNEXEOS.com or call 1-855-297-5903 to learn more. What is HERNEXEOS (zongertinib tablets)? HERNEXEOS is a prescription medicine used to treat adults with a type of lung cancer called non-squamous non-small cell lung cancer (NSCLC) that: Your healthcare provider will perform a test to make sure HERNEXEOS is right for you. It is not known if HERNEXEOS is safe and effective in children. References: 1 HERNEXEOS Prescribing Information 2 Heymach, J. et al. Zongertinib in previously treated HER2-mutant non-small cell lung cancer. N Engl J Med. 2025;01-13. 3 Baraibar I, et al. Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC. Crit Rev Oncol Hematol. 2020;148:102906. 4 Li, B.T. et al. Trastuzumab Deruxtecan in HER2-Mutant Non–Small-Cell Lung Cancer. N Engl J Med. 2022;386:241–51 5 Zeng J, Ma W, Young RB, Li T. Targeting HER2 genomic alterations in non-small cell lung cancer. J Natl Cancer Cent. 2021 May 3;1(2):58-73. 6 International Agency for Research on Cancer – World Health Organization. Rates of trachea, bronchus and lung cancer. Available at: https://gco.iarc.fr/tomorrow/en (Accessed: January 2025). 7 American Cancer Society. Lung Cancer Early Detection, Diagnosis, and Staging. Available at: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/signs-symptoms.html (Accessed: January 2025). 8 Casal-Mouriño, A. et al. Epidemiology of stage III lung cancer: frequency, diagnostic characteristics, and survival. Transl Lung Cancer Res. 2021;10(1):506-518. 9 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER). 5-Year Survival Rates. https://www.seer.cancer.gov/csr/1975_2016/results_merged/topic_survival.pdf (Accessed July 2025). 10 Belaroussi, Y. et al. Survival outcomes of patients with metastatic non-small cell lung cancer receiving chemotherapy or immunotherapy as first-line in a real-life setting. Sci Rep. 2023.13, 9584. 11 Simeone, J. C. et al. Treatment patterns and overall survival in metastatic non-small-cell lung cancer in a real-world US setting. Fut. Oncol. Lond. Engl. 2019. 15(30), 3491–3502. 12 Valentine, T. R. et al. Illness Perceptions and Psychological and Physical Symptoms in Newly Diagnosed Lung Cancer. Health Psychol. 2022 Jun; 41(6): 379–388. 13 Andersen, B. L. et al. Newly diagnosed patients with advanced non-small cell lung cancer: A clinical description of those with moderate to severe depressive symptoms. Lung Cancer. 2020 Jul;145:195-204. 14 Presley, C. J. et al. Functional Disability Among Older Versus Younger Adults With Advanced Non–Small-Cell Lung Cancer. JCO Oncol Pract. 2021 May 3;17(6):e848–e858. SOURCE: Boehringer Ingelheim

Boehringer Ingelheim's Hernexeos is one of two new drug approvals the company is expecting this year. With the FDA approval of its zongertinib in certain non-small cell lung cancer (NSCLC) patients, 175-year-old Boehringer Ingelheim is entering the oncology market.Zongertinib, which will be sold as Hernexeos, was specifically cleared to treat previously treated NSCLC patients who have the relatively rare HER2 activating mutations in the tyrosine kinase domain (TKD).It’s a patient population that has a “huge unmet need” and is estimated to be comprised of about 40,000 people across the globe, Boehringer’s senior vice president of oncology, Itziar Canamasas, Ph.D., told Fierce Pharma in a recent interview. The mutated cancer type occurs in approximately 2% to 4% of NSCLC cases. Hernexeos is now the first FDA-approved oral treatment that can specifically target the disease. It marks a welcome chemo-free treatment option for patients as well as a “big entry” for Boehringer into the oncology space, Canamasas said. The drug's benefits were supported by the Beamion Lung-1 phase 1b trial, in which Hernexeos proved an objective response rate of 75% among 71 patients who had received prior platinum-based chemotherapy but not a HER2-targeted tyrosine kinase inhibitor or antibody-drug conjugate, according to the FDA. Within this cohort, 58% of patient had their responses lasting for at least six months.Among 34 patients previously treated with platinum-based chemotherapy and a HER2-targeted ADC, the objective response rate was 44%, with 27% having a duration of response of at least six months.Additional data published in April showed that the drug may help patients in the first cohort live without their disease getting worse for a median of 12.4 months, although the data were immature. The results signaled Hernexeos' potential to "impact clinical practice," Boehringer said at the time. All in all, “nearly every patient” benefited from treatment in the study, Canamasas said, referring to a 96% disease control rate revealed in April.Fewer than 3 in 10 patients are alive five years after a diagnosis of HER2-mutant advanced NSCLC, according to Boehringer, with advanced disease causing a “physical, psychological, and emotional impact” in patients' daily lives. The mutation is linked with a high incidence of brain metastasis.As it stands, AstraZeneca and Daiichi Sankyo’s Enhertu is the only FDA-approved regimen cleared to treat the HER2-mutant NSCLC population, but that option comes with “chemotherapy-like side effects,” thoracic medical oncologist and lead study investigator Joshua Sabari, M.D., told Fierce Pharma over email. Hernexeos’ data, meanwhile, prove the drug as “truly a targeted therapy” with low dose reduction rates, “very low” discontinuation and very low-grade rash rate, he said.“To me, it's a game changer—a truly targeted agent for our patients with optimal activity, selectivity as well as quality of life and side effect profile,” Sabari said, adding that “most patients on this therapy do extremely well for prolonged periods of time with excellent quality of life.”The lung disease nod is just the start of Boehringer’s journey with Hernexeos, which Canamasas called a “pipeline in a product.” Next, the company hopes to be able to position the drug as a first-line treatment in its NSCLC indication and is currently studying the potential in a phase 3 trial, while additional explorations in pan tumors, breast cancer and gastric cancer are ongoing. The drug's current indication is granted under the FDA accelerated approval pathway, and Boehringer is on the hook to provide confirmatory evidence to further verify the drug's profile. Hernexeos headlines Boehringer’s cancer care ambitions, and more is on the horizon. The company’s oncology pipeline includes a T-cell engager that’s currently being evaluated in mid-stage trials in extrapulmonary neuroendocrine carcinoma and small-cell lung cancer. Oncology is certainly an area that Boehringer is putting its chips behind, as it recently opened a 27 million Swiss franc ($33.6 million) ADC R&D spot in Basel, Switzerland.Outside of oncology and Hernexeos, the company is awaiting another new drug approval this year for its PDE4B inhibitor nerandomilast in idiopathic pulmonary fibrosis. Boehringer expects to launch both treatments this year and, further ahead, is plotting 15 launches through 2030.