FDA Grants Advanced Therapy Designation to Zenocutuzumab (Zeno) for Treating NRG1+ Pancreatic Cancer
Saturday, July 01, 2023
Merus NV, a clinical-stage oncology company specializing in the development of full-length multispecific antibodies for cancer treatment, announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to zenocutuzumab (Zeno) for the treatment of advanced, unresectable, or metastatic NRG1 fusion carcinoma (NRG1+) of the pancreas. This designation is intended for patients who have experienced treatment progression with prior systemic therapy or have no satisfactory alternative treatment options.
Prior to this, Zeno had received Fast Track Designation for the treatment of metastatic solid tumors with NRG1 gene fusions (NRG1+ cancer) after failing standard therapy, as well as Orphan Drug Designation for pancreatic cancer treatment.
The FDA's decision to grant the Advanced Therapy designation was based on data from the ongoing Phase I/II eNRGy study and Early Access Program (EAP), which assess the safety and anti-tumor activity of Zeno as a monotherapy in NRG1+ cancer. Notably, over 175 patients with NRG1+ cancer have already been treated with Zeno monotherapy as of June 2023.
Obtaining Advanced Therapy status allows for an expedited development and testing process, as well as increased FDA guidance and priority review. Merus plans to establish a commercialization partnership to ensure broad access to Zeno for patients with NRG1+ cancers, pending approval. Additionally, Merus is evaluating the use of Zeno in combination with androgen deprivation therapy in castration-resistant prostate cancer (CRPC), regardless of NRG1+ status, with initial clinical data expected to be reported in the second half of 2023. Furthermore, Zeno is being investigated in combination with afatinib in NRG1 gene fusion-positive non-small cell lung cancer (NSCLC) patients.
Zeno, an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics® developed by Merus, targets the neuregulin/HER3 tumor signaling pathway in NRG1+ solid tumors. It acts by binding to HER2 and effectively blocking HER3's interaction with its ligand NRG1 or NRG1 fusion proteins. Preclinical studies have shown that Zeno inhibits HER2/HER3 heterodimer formation, leading to the inhibition of oncogenic signaling pathways, suppression of tumor cell proliferation, and disruption of tumor cell survival.