The FDA has issued a complete response letter (CRL) to the new drug application (NDA) seeking the approval of the liver imaging agent Orviglance (formerly Mangoral) for use in the detection and localization of liver metastases in patients with severe kidney impairment.1,2
The regulatory agency informed Ascelia Pharma, the developer of Orviglance, that it is not able to approve the imaging agent in its current form and also requires additional product documentation and clinical data before an approval may be granted.1
Ascelia Pharma plans to meet with the FDA to discuss the CRL and expedite future regulatory plans for Orviglance for this indication. This includes plans to request a Type A meeting with the FDA to better understand the issues with Orviglance and the NDA.
“We remain confident in Orviglance and are committed to making it available to patients,” Magnus Corfitzen, chief executive officer of Ascelia Pharma, stated in a news release. “Our focus now is to work with the FDA to identify an expedited path forward. We will provide further updates when appropriate.”
Orviglance CRL for Liver Imaging in Patients With Severe Kidney Impairment
- The FDA issued a CRL to the liver imaging agent Orviglance, declining to approve it in its current form and requesting additional product documentation and clinical data before an approval can be granted.
- Orviglance is a novel, liver-specific, manganese-based oral contrast agent designed to detect and localize focal liver lesions and metastases via MRI in patients with severe kidney impairment and for whom standard gadolinium-based contrast agents are not medically advisable.
- The NDA was supported by data from the SPARKLE trial, in which Orviglance significantly improved focal liver lesion visualization compared with unenhanced MRI across all 3 blinded independent readers (P < .001), with a safety profile limited mainly to mild-to-moderate nausea and no drug-related serious AEs.
What is the mechanism of action of Orviglance?
Orviglance is a novel, liver-specific, manganese-based, oral contrast agent that is being developed in phase 3 studies to detect and locate liver metastases via MRI in patients in whom the use of standard gadolinium-based contrast agents is not medically advisable or in whom those agents cannot be administered.2 Orviglance uses manganese chloride tetrahydrate and is designed to improve the detection and visualization of focal liver lesions, including primary tumors and liver metastases, in patients with severe kidney impairment.
What is the regulatory history of Orviglance?
On November 15, 2025, the FDA accepted for review the NDA seeking the approval of Orviglance for the visualization of liver lesions in patients with impaired kidney function.3 This NDA was supported by findings from 9 clinical studies across 286 patients and healthy volunteers that consistently showed positive efficacy and safety data. In the phase 3 SPARKLE trial (NCT04119843), Orviglance was shown to significantly improve focal liver lesion visualization compared with unenhanced MRI in patients with suspected or known focal liver lesions and severely impaired kidney function, across all 3 blinded independent readers, meeting the trial’s primary end point (P < .001).2,3 The reliability of the data, including an acceptable level of variability, was deemed strong and conclusive by all 3 readers.
Common adverse effects (AEs) in SPARKLE were deemed consistent with those seen in previous Orviglance studies and included mild-to-moderate nausea. The investigators observed no serious AEs related to the drug.
Orviglance was also previously granted orphan drug designation from the FDA.2
What was the design of the SPARKLE trial of Orviglance in patients with impaired kidney function?
The global SPARKLE trial enrolled 85 patients from 32 sites across the US, Europe, and Latin America. Each patient was their own control, and underwent unenhanced MRI plus Orviglance and unenhanced MRI alone. Centralized evaluation was conducted by 3 blinded, independent radiologists. Patients were followed for safety for a maximum of 7 days.
What prior Orviglance research has also read out?
Prior to SPARKLE, 4 phase 1 studies showed the safety, absorption, and signal intensity of Orviglance across 126 healthy volunteers, including dose-finding, hepatic impairment, and food effect data. Additionally, 4 phase 2 studies showed the efficacy and safety of the agent across 75 patients with known metastases. Furthermore, a centralized evaluation of a phase 2 trial with 3 readers confirmed the efficacy of Orviglance compared with gadolinium and unenhanced MRI in 20 patients with liver metastases.
References
- Ascelia Pharma provides update on the Orviglance NDA. News release. Ascelia Pharma. July 3, 2026. Accessed July 6, 2026. https://www.ascelia.com/mfn_news/ascelia-pharma-provides-update-on-the-orviglance-nda/
- Orviglance. Ascelia Pharma. Accessed July 6, 2026. https://www.ascelia.com/pipeline/orviglance/
- Ascelia Pharma announces FDA acceptance of Orviglance new drug application for review. News release. Ascelia Pharma. November 15, 2025. Accessed July 6, 2026. https://www.ascelia.com/mfn_news/ascelia-pharma-announces-fda-acceptance-of-orviglance-new-drug-application-for-review/
