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# Ascelia Clarifies CRL on MRI Agent After Public Release
- URL: https://www.fdaweb.com/ascelia-clarifies-crl-on-mri-agent-after-public-release/
- Published: 2026-07-13T12:00:00.000Z
- Updated: 2026-09-14T13:42:46.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5161445

Ascelia Pharma is pushing back against FDA's recent public release of a Complete Response Letter (CRL) for its MRI contrast agent Orviglance, arguing that the agency's concerns center on the image-reading process used in its pivotal Phase 3 study rather than deficiencies in the study itself. The company said it is preparing for a Type A meeting with FDA to discuss the issues and identify a path forward for the NDA.

The [7/10-posted CRL](https://download.open.fda.gov/crl/CRL%5FNDA220544%5F20260702%5FRedacted.pdf?ref=fdaweb.com) states that the NDA's single adequate and well-controlled study failed to meet its prespecified success criteria because only one of the three original blinded image readers demonstrated superiority of Orviglance over non-contrast MRI for all three co-primary endpoints. FDA also rejected the company's subsequent post hoc image re-read, saying it "was not adequately justified" and may have introduced bias because the new readers could have been influenced by knowledge gained from the initial review. The agency concluded that the study was not adequate and well controlled and recommended conducting a new clinical trial with appropriate reader training that includes lesion scoring using the complete set of pre-contrast images.

In an update issued 7/12 in response to the CRL’s release, the Swedish biopharmaceutical company says it continues to believe its Phase 3 SPARKLE trial was "adequate and well-controlled" and generated a comprehensive dataset for evaluating the product's clinical performance. According to the company, the study was conducted in accordance with its protocol and included all planned MRI sequences, including T1-weighted, T2-weighted and diffusion-weighted imaging. Orviglance's active ingredient, manganese, functions as a T1-enhancing contrast agent.

The company acknowledges that problems identified during the initial image reading process prevented efficacy conclusions from being drawn from those original assessments, an issue it has disclosed previously. Ascelia says it subsequently implemented a new image review process using independent, blinded radiologists who had no prior exposure to the SPARKLE images or earlier reading results. The re-read was conducted under predefined procedures intended to provide a consistent evaluation of the imaging data.

The company adds that it discussed the original image-reading issues and its proposed approach with FDA during the review process and incorporated the agency's feedback into the NDA submission.

In addition to the clinical issues, Ascelia notes FDA also raised questions related to product documentation. The company said it expects to address those issues in the near term.