FDA grants Orphan Drug Designation to zenocutuzumab (BIZENGRI®) for NRG1 fusion-positive cholangiocarcinoma, supporting targeted treatment development
Written By: Nikita Jha BPharm
Reviewed By: Pharmacally Editorial Team
Partner Therapeutics announced that the U.S. Food and Drug Administration has granted Orphan Drug Designation (ODD) to zenocutuzumab-zbco for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma harbouring NRG1 gene fusions.
NRG1 gene fusions are rare oncogenic drivers that result from structural DNA rearrangements and typically occur without other common oncogenic alterations. These fusions produce chimeric ligands that bind to HER3, triggering HER2/HER3 signalling and promoting Tumor growth.
Zenocutuzumab-zbco is a bispecific antibody designed to block HER2/HER3 dimerization and prevent NRG1 fusion interactions with HER3, suppressing downstream cancer-promoting pathways. Identification of eligible patients relies on comprehensive molecular profiling using both DNA- and RNA-based next-generation sequencing.
Zenocutuzumab-zbco, marketed as BIZENGRI®, previously received Breakthrough Therapy Designation in October 2025 and was granted accelerated approval in December 2024 for adults with NRG1 fusion-positive non-small cell lung cancer and pancreatic ductal adenocarcinoma following prior therapy.
Commenting on the designation, Juan W. Valle, MD, Chief Medical Officer of the Cholangiocarcinoma Foundation, highlighted the urgent need for effective, biomarker-driven treatments for patients with this aggressive disease.
Cholangiocarcinoma is a rare and aggressive bile duct cancer; most often diagnosed at an advanced stage. Approximately 8,000 cases are reported annually in the United States, and the five-year survival rate remains below 15 percent, reflecting the limited effectiveness of available therapies.
Current first-line systemic treatments provide modest benefit, with overall response rates of 26 to 29% and median overall survival of 11.7 to 12.8 months. Outcomes worsen after progression, as second-line FOLFOX chemotherapy achieves response rates of about 5% and a median overall survival of 6.2 months.
The FDA’s Orphan Drug Designation is intended for therapies targeting diseases affecting fewer than 200,000 people in the United States and provides incentives such as market exclusivity upon approval, user-fee waivers, and regulatory support during development.
For full prescribing information, including safety details, boxed warning, precautions, and contraindications, please refer to the BIZENGRI® Prescribing Information at: https://bizengri.com/pdf/pi.pdf
Reference
Zenocutuzumab‑zbco Receives FDA Orphan Drug Designation for Treatment of Cholangiocarcinoma, 05 February 2026, https://www.partnertx.com/zenocutuzumab%e2%80%91zbco-receives-fda-orphan-drug-designation-for-treatment-of-cholangiocarcinoma/