FDA rejects application for new oral MR imaging contrast agent

The U.S. Food and Drug Administration recently rejected an application for a new oral contrast imaging agent, citing concerns related to radiologists' reads during clinical trials. 

Biotechnology firm Ascelia Pharma is working to roll out Orviglance, a novel manganese-based product for visualizing focal liver lesions during MRI. However, the Sweden-headquartered company suffered a setback earlier this month, when the FDA issued a formal letter, contending it “cannot approve this application in its present form.”

“In the absence of a successful adequate and well-controlled study, substantial evidence of effectiveness has not been demonstrated,” the agency said in its July 2 rejection letter.

The FDA noted that the clinical study testing Orviglance’s effectiveness did not meet its planned success criteria. This because only 1 of the 3 initial readers demonstrated the superiority of the contrasted images to the noncontrast ones. Plus, the follow-up reevaluation of images was “not adequately justified,” potentially introducing bias into the training of new readers, due to their knowledge of the images and previous read results. The FDA is now recommending a new controlled study with “appropriate reader training,” which includes lesion scoring with the complete set of precontrast images. 

Ascelia Pharma said in a July 12 news update that it was preparing for a meeting with the FDA to better understand the concerns outlined by the agency. It views the issues raised as relating to the image-reading process, rather than the drug itself, and is providing additional context to help clarify its position. Ascelia considers the phase 3 study in question to be “an adequate and well-controlled study,” with data providing a “comprehensive and robust basis for evaluating the clinical performance of Orviglance.” 

The pharma firm said it had already implemented a new image reading process, using independent, blinded readers with no knowledge of prior reading results. These updates were discussed with the FDA, and the agency’s feedback was incorporated into the New Drug Application in question. 

“Ascelia intends to provide a further update following the planned meeting with the FDA and receipt of the official meeting minutes,” it noted. “The company welcomes the opportunity to discuss the matters outlined in the complete response letter with the FDA.”

Pharma Voice first reported news of the rejection on July 23. The outlet notes that these FDA response letters were previously not made available to the public. However, the agency in 2025 began publishing troves of responses in a push for “radical transparency.” This latest batch included 14 letters, among them, the response to Ascelia Pharma. It came days after the FDA confirmed a pause in its transparency plans, which were challenged by an anonymous pharma company contending these disclosures may violate the law. 

The FDA also recently proposed a new rule that would eliminate the “longstanding presumption that the mere existence of a marketing application constitutes confidential commercial information,” according to Pharma Voice.