Sparkle: A Multicenter, Open-label Study To Evaluate The Safety And Diagnostic Efficacy Of Ace-mbca In Patients With Known Or Suspected And Severe Renal Impairment

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.

By - Eeshan Aggarwal

Reference: American Society of Nephrology. Presented at Kidney Week 2024.