FDA Grants Orphan Drug Designation to Zenocutuzumab-zbco for Cholangiocarcinoma Treatment

FDA Grants Orphan Drug Status to Zenocutuzumab-zbco

On February 5, 2026, Partner Therapeutics, Inc. (PTx) announced that the FDA has granted Orphan Drug Designation (ODD) to its investigational therapeutic agent, zenocutuzumab-zbco. This decision represents a pivotal moment in the development of treatment options for adults suffering from advanced unresectable or metastatic cholangiocarcinoma, a rare cancer affecting the bile ducts. Zenocutuzumab-zbco is being specifically developed for patients who harbor a NRG1 gene fusion, marking a significant step-forward in targeted cancer therapy.

Understanding Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a particularly aggressive malignancy, and due to its rarity—approximately 8,000 new cases per year in the United States—it tends to be diagnosed at an advanced stage. The survival rates for CCA are alarmingly low, with less than 15% of patients surviving five years after diagnosis. Traditional treatment options yield modest effectiveness, underscoring the pressing need for innovative therapeutic approaches.

The NRG1 gene fusions that zenocutuzumab targets result from structural DNA rearrangements, typically occurring without other oncogenic alterations. The identification of these fusions is crucial for determining the most effective treatment plan, and it involves advanced techniques such as tissue-based RNA and DNA sequencing.

The Current Landscape of Treatment Options

Existing first-line systemic options for CCA show overall response rates (ORRs) ranging from 26% to 29%. Median overall survival (OS) rates clock in at 11.7 to 12.8 months. In the second-line setting, treatment regimens such as FOLFOX exhibit an ORR of only 5% along with a PFS of approximately four months, and an OS of merely 6.2 months. These statistics highlight the urgent need for new therapies that offer improved efficacy and outcomes.

Zenocutuzumab-zbco stands out as it aims to provide effective treatment for those patients who specifically have NRG1 gene fusions, a context where current treatment options have fallen short.

Significance of FDA's Orphan Drug Designation

Orphan Drug Designation is a regulatory classification provided by the FDA to facilitate the development of therapies for rare diseases affecting fewer than 200,000 individuals in the U.S. By receiving ODD, zenocutuzumab benefits from several advantages, including potential seven years of market exclusivity post-approval, exemptions from certain FDA fees, eligibility for tax incentives related to clinical trials, and enhanced collaboration with the FDA during the development process.

Juan W. Valle, MD, Chief Medical Officer at the Cholangiocarcinoma Foundation, emphasized the importance of this designation, noting, "Receiving Orphan Drug Designation for zenocutuzumab in patients with CCA harboring the NRG1 gene fusion is a significant regulatory milestone. It underlines the urgent necessity for developing effective alternatives for this aggressive cancer."

Previous Achievements

Zenocutuzumab-zbco is not new to accolades; it received Breakthrough Therapy Designation from the FDA in October 2025 and gained accelerated approval in December 2024 for adult patients with advanced unresectable or metastatic non-small cell lung cancer and pancreatic ductal adenocarcinoma harboring NRG1 gene fusions following prior treatments. These designations have paved the way for its progression toward broader clinical application in oncological practice.

Understanding NRG1 Gene Fusions

The unique characteristic of NRG1 fusions is they create oncogenic chimeric ligands as opposed to traditional gene fusions that produce chimeric receptors found in common alterations like NTRK or ALK fusions. When activated, these ligands target HER3, which in turn instigates cellular growth and proliferation pathways that fuel cancer progression. Zenocutuzumab-zbco functions as a bispecific antibody capable of blocking HER2/HER3 interactions, offering a pathway to disrupt these detrimental signaling cascades.

Conclusion

Given the dismal prognosis commonly associated with cholangiocarcinoma, the development of zenocutuzumab represents a beacon of hope for patients and healthcare providers alike. As highlighted by Partner Therapeutics, through comprehensive molecular analysis, the identification and targeting of actionable NRG1 fusions exemplify the shift toward personalized medicine. This innovative approach may ultimately lead to much-needed advancements in treatment for those affected by this challenging disease. For more information on the ongoing eNRGy trial, visit Partner Therapeutics.