The clinical development of Mangoral specifically target patients with severe renal insufficiency in need of a liver MRI. These patients are at risk of Nephrogenic Systemic Fibrosis (“NSF”), a serious and potentially fatal condition caused by exposure to gadolinium in gadolinium based contrast agents.
Mangoral is being developed as a targeted medical imaging drug for diagnostic MRI for visualization of metastatic focal liver lesions in patients where use of gadolinium based contrast agents (GBCAs) may be medically inadvisable or where GBCAs cannot be administered. For this indication US Orphan Drug Designation has been obtained from FDA for Mangoral. The targeted patient population is cancer patients with known or suspected liver metastases and severe renal insufficiency. Mangoral addresses a significant unmet medical need related to detecting and localizing liver metastases and may therefore substantially increase the survival rate for cancer patients. There are currently no FDA or EMA approved, non-gadolinium MRI medical imaging drugs on the market, meaning that there are no competing products with Mangoral’s properties.
Six Phase I and Phase II clinical trials on Mangoral have been completed without any serious safety concerns. The product candidate is considered safe, and the studies have provided strong support for Mangoral as an effective liver specific non-gadolinium MRI imaging drug. Based on these results, Ascelia has decided to continue the clinical development and commercialization of Mangoral on its own and/or in collaboration with suitable partners. Ascelia has therefore established a development program for Mangoral, consisting of a pivotal Phase III efficacy study and two supportive studies (one special population study and one food effect study).
PLANNED STUDIES ON MANGORAL:
The Phase III pivotal study aims to demonstrate the safety and efficacy of Mangoral in terms of improved lesion visualization as compared to unenhanced MRI, with each patient being his/her own control subject. It will be a multicenter and multinational study of Mangoral in up to 200 patients with severely reduced renal function and with known or suspected liver metastases. Primary efficacy, in terms of lesion visualization compared to unenhanced MRI, will be evaluated by three independent blinded readers. MRI will be performed before and within few hours after oral Mangoral administration, and basic safety parameters will be evaluated for 72 hours after administration of Mangoral.
The overall objective of the special populations hepatic study will be to assess the influence of hepatic impairment on the safety, pharmacokinetics and pharmacodynamics of Mangoral in patients with different degrees of hepatic impairment. The study is planned to include a subgroup of patients with known hepatocellular carcinoma (HCC) to explore potential label expansion of Mangoral into this indication. It will be a dose-escalation study of up to 50 patients performed in a few study sites.
The food effect study is based on common regulatory requirements and its objective will be to evaluate the food effect on the bioavailability of Mangoral. The study is planned as a crossover study of Mangoral administered in healthy subjects in fasting condition vs fed condition. It will be performed in a single study site and is planned to be completed before a New Drug Application (NDA) of Mangoral is submitted to the FDA.