Zongertinib

Boehringer Ingelheim’s oral tyrosine kinase inhibitor, Hernexeos, has received accelerated approval from the FDA. Image credit: create jobs 51 via Shutterstock.com. Boehringer Ingelheim has received fast-track approval from the US Food and Drug Administration (FDA) for its targeted therapy, Hernexeos (zongertinib tablets) , to treat non-small cell lung cancer (NSCLC). This approval succeeds the positive results of the Phase Ib Beamion-LUNG 1 trial (NCT04886804), with the oral tyrosine kinase inhibitor (TKI) demonstrating an objective response rate (ORR) of 75% in patients with HER2-positive NSCLC who had received prior lines of platinum-based chemotherapy. Its FDA approval makes it the first oral treatment for HER2-positive NSCLC. Hernexeos also triggered a duration of response (DOR) of more than six months in 58% of the 71 patients previously treated with chemotherapy alone, while 27% of the 34 individuals with prior exposure to chemotherapy and a HER2 targeted therapy experienced a DOR of this length. Impacting 2%-4% of patients diagnosed with NSCLC, HER2 mutations are associated with poor prognosis and a higher risk of brain metastasis, while treatment options are highly limited in this population. Due to Hernexeos’ potential to fulfil unmet needs in this indication, the FDA granted Boehringer priority review and breakthrough therapy designation last year. The therapy’s full approval will likely rely on verification of clinical benefit in a confirmatory trial. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence Dr John Heymach, co-ordinating investigator on the Beamion-LUNG 1 trial and chair of thoracic/head and neck medical oncology at the MD Anderson Cancer Centre, said: “The approval of zongertinib offers an effective and targeted treatment option for patients with HER2-mutant NSCLC in the US that not only elicits a durable response, but also has a manageable safety profile. “In a patient population where there are currently limited treatment options, this approval represents a significant advancement in cancer care.” HER2-targeted therapy race heats up Though the current standard of care (SoC) for patients with HER2-mutated NSCLC still revolves around a platinum-based chemotherapy regimen, physicians are increasingly prescribing targeted therapies to improve outcomes. A notable example of this is AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate (ADC ) Enhertu (trastuzumab deruxtecan), which became the first HER2-targeting therapy to receive approval for NSCLC in 2022. Following its accelerated FDA approval, the drug has already reached blockbuster status – raking in $4.1bn in 2024 for the company, according to Pharmaceutical Technology ’s parent company, GlobalData. GlobalData predicts that the drug is on track to pull in $14.6bn by 2031, highlighting the lucrative nature of the targeted oncology market. However, Hernexeos has demonstrated a higher ORR of 75% compared with Enhertu’s 56% in the DESTINY-Lung02 trial. The TKI has also proved efficacious in patients who had previously received treatment with an ADC, suggesting that the TKI could absorb some of Enhertu’s market share. Looking ahead, the drug may also face competition from other targeted therapies currently in Phase III clinical trials, with GlobalData giving Bayer’s TKI sevabertinib a likelihood of approval (LoA) score of 81% in this indication. Pharmaceutical Technology Excellence Awards - The Benefits of Entering Gain the recognition you deserve! The Pharmaceutical Technology Excellence Awards celebrate innovation, leadership, and impact. By entering, you showcase your achievements, elevate your industry profile, and position yourself among top leaders driving pharmaceutical advancements. Don’t miss your chance to stand out—submit your entry today! Nominate Now

iStock, beast01 Phase III data show Hernexeos can elicit a confirmed objective response rate of 48% in patients with HER2-mutated NSCLC who had previously been treated with a directed antibody-drug conjugate. The FDA signed off on Boehringer Ingelheim’s kinase inhibitor zongertinib for the treatment of certain patients with non-small cell lung cancer. The drug, to be marketed under the brand name Hernexeos, marks Boehringer Ingelheim’s debut in the cancer space after 140 years in business. Hernexeos is specifically indicated for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC), whose tumors harbor HER2 tyrosine kinase domain (TKD)-activating mutations, according to the FDA’s announcement of the approval on Friday. The regulator cleared Hernexeos under its accelerated pathway. The drug’s continued approval will be contingent on a confirmatory trial. Data from the Phase I Beamion LUNG-1 trial supported Friday’s approval. Data published in September 2024 showed Hernexeos elicited a 66.7% objective response rate (ORR), as well as an intracranial response rate of 33% in patients with brain metastases. In this subpopulation, disease control rate was 74%. Boehringer released updated and more detailed data earlier this year, showing that in patients with TKD mutations, the confirmed ORR was 71%, with a median progression-free survival of 12.4 months. Meanwhile, confirmed ORR was 48% in patients with TKD mutations who had previously been treated with a HER2-directed antibody-drug conjugate. Hernexeos was also safe overall, as per the early-stage readout, with only 2.9% of treated patients dropping out of the trial. There were no documented instances of drug-related interstitial lung disease. Shashank Deshpande, head of Human Pharma at Boehringer, said in a statement on Friday that Hernexeos has the “potential to reset the benchmark for those living with HER2-mutant advanced non-small cell lung cancer,” adding that the disease is often associated with a poor prognosis. Patients with metastatic NSCLC face a 5-year survival rate of less than 10% , according to data from the National Cancer Institute. HER2 mutations, which occur in 2% to 4% of all NSCLC cases, are linked to worse prognoses and brain metastasis. Designed to be taken orally, Hernexeos addresses an underlying disease pathway in NSCLC by selectively and irreversibly binding to HER2, in turn preventing cell growth and division dependent on this signaling cascade. With its approval on Friday, Hernexeos will join AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu in the HER2-mutant NSCLC arena. Enhertu was approved for this indication in August 2022 and is also indicated for different types of breast cancer and HER2-positive solid tumors. Last year, Enhertu made nearly $2 billion worldwide .