SPARKLE: A MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND DIAGNOSTIC EFFICACY OF ACE-MBCA

New Contrast Agent Offers Hope for Liver MRI in Kidney-Impaired Patients

A groundbreaking phase III study has demonstrated the safety and efficacy of ACE-MBCA (proposed trade name Orviglance), a manganese-based oral liver-specific MRI contrast agent for patients with severe renal impairment. This population, typically excluded from contrast agent studies due to safety concerns, faces significant risks with traditional Gadolinium-Based Contrast Agents (GBCAs), which carry a black-box warning from the FDA.

Addressing a Critical Gap in Imaging

Over 35 million Americans suffer from renal disease with severely affected patients at greater risk of adverse effects from GBCAs due to their kidneys' inability to efficiently eliminate the agents. ACE-MBCA, developed by Ascelia Pharma offers a safer alternative for liver MRI in this vulnerable group. By targeting focal liver lesions in patients with severe renal impairment, this study addresses a critical gap in diagnostic imaging options.

Study Design

The global trial enrolled 85 patients with known or suspected focal liver lesions and severe renal impairment. Each patient underwent liver MRI both before and 4 hours after receiving a single 800 mg dose of ACE-MBCA. Independent reviewers assessed lesion contrast (LC) and border delineation (BD) on a qualitative scale ranging from 1 (poor) to 4 (excellent). Safety was closely monitored at intervals of 24-, 48- and 120-hours post-administration.

Significant Improvement in Imaging Quality

The results revealed a statistically significant improvement in diagnostic imaging efficacy with ACE-MBCA:

• Lesion Contrast (LC): Increased by 0.65 to 0.95 points across the three reviewers (p<0.001).
• Border Delineation (BD): Improved by 0.81 to 1.02 points (p<0.001).

This combined contrast-enhanced and unenhanced MRI (CMRI) approach proved markedly superior to unenhanced MRI alone, enhancing the visualization of focal liver lesions.

Safety Profile

ACE-MBCA demonstrated a favorable safety profile, with no drug-related serious adverse events or deaths reported. The most common mild to moderate side effects included:

• Nausea (16.1%)
• Diarrhea (13.8%)
• Vomiting (9.2%)
• Increased blood urea (3.4%)

No patients were withdrawn from the study due to adverse events.

A Promising Diagnostic Tool

The findings confirm ACE-MBCA’s potential as a safer and effective alternative for liver MRI in patients with severe kidney impairment, who currently lack viable contrast-enhanced imaging options. By significantly improving diagnostic accuracy without the risks associated with GBCAs, ACE-MBCA offers hope for enhanced liver lesion detection and management in this high-risk population.

As research progresses, ACE-MBCA could represent a major advancement in imaging for patients with both liver and kidney conditions, addressing unmet needs in diagnostic medicine.