FDA Rejects Manganese Chloride Tetrahydrate for Liver MRI in Renal Impairment

Ascelia Pharma AB has received a complete response letter (CRL) from the US FDA for manganese chloride tetrahydrate (Orviglance), an investigational oral contrast agent developed for MRI of focal liver lesions in patients with severe renal impairment.¹ The Malmö, Sweden-based biotechnology company announced that the FDA is currently unable to approve the new drug application (NDA) in its present form and has requested additional clinical data and product documentation. The decision arrived on the drug's Prescription Drug User Fee Act (PDUFA) action date of July 3, 2026.

Ascelia said it plans to request a type A meeting with the FDA to clarify the agency's concerns and pursue what the company called an expedited path forward.

"We remain confident in [manganese chloride tetrahydrate] and are committed to making it available to patients," said Magnus Corfitzen, CEO of Ascelia Pharma, 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."

Clinical Rationale

Manganese chloride tetrahydrate is designed to address an imaging gap for patients with severely impaired kidney function who require contrast-enhanced liver MRI to detect and characterize focal liver lesions, including primary tumors and metastases. Gadolinium-based contrast agents, the current standard for liver MRI, carry FDA black-box warnings in this population because of the risk of nephrogenic systemic fibrosis, a serious and potentially fatal fibrosing condition linked to gadolinium retention in patients with reduced renal clearance. As a result, patients with advanced kidney disease are frequently imaged without contrast, which can limit lesion detection and characterization. Manganese chloride tetrahydrate, administered orally, was developed as a gadolinium-free alternative for this population and holds FDA orphan drug designation.

Trial Evidence

The NDA was supported by a 9-study clinical program that included the pivotal, multicenter, open-label phase 3 SPARKLE trial (NCT04119843), which evaluated the safety and diagnostic efficacy of the agent in patients with known or suspected focal liver lesions and severe renal impairment.² According to the company, the trial met its primary end point, with manganese chloride tetrahydrate significantly improving visualization of focal liver lesions compared with unenhanced MRI, an effect reported as statistically significant across 3 independent, blinded readers.¹ In an earlier comparative study presented at the 2021 Radiological Society of North America annual meeting, contrast-enhanced imaging with the agent showed lesion detection and visualization performance comparable to the gadolinium-based agent gadobenate dimeglumine (Multihance). Across the early- and late-phase studies, diarrhea and nausea were the most frequently reported adverse events, occurring more often than is typical with gadolinium-based agents, though rates reportedly declined in the Phase 3 trial at the selected 800-mg dose.

Regulatory Timeline

Ascelia submitted the NDA to the FDA in September 2025. The agency accepted the application for standard review in November 2025 and set the July 3, 2026, PDUFA date. The CRL did not specify the nature of the requested clinical data, and Ascelia has not yet disclosed further detail on the deficiencies cited by the agency.

Clinical Implications

If manganese chloride tetrahydrate is ultimately approved, it would be positioned as the first oral, nongadolinium contrast option for liver MRI in patients with severe renal impairment, a population that currently has no dedicated on-label contrast agent and is often imaged without one. The CRL means that outcome remains pending, and clinicians managing patients with liver lesions and coexisting severe renal impairment should continue to rely on existing imaging protocols, including unenhanced MRI or judicious, guideline-directed use of gadolinium-based agents, until the regulatory pathway is resolved.

REFERENCES

1. Ascelia Pharma Provides Update on the Orviglance NDA. News release. Ascelia Pharma. July 5, 2026. Accessed July 7, 2026. https://tinyurl.com/3j8kms52

2. Safety and Diagnostic Efficacy of Mangoral in Participants With Focal Liver Lesions and Reduced Kidney Function (SPARKLE). ClinicalTrials.gov. Updated February 6, 2025. Accessed July 7, 2026. https://clinicaltrials.gov/study/NCT04119843