A new paradigm within MRI: development of a novel manganese based contrast agent with high commercial value

Magnetic Resonance Imaging (MRI) is a powerful imaging method to detect and characterize disease in humans. The detection ability is improved by the administration of MRI contrast agents (MRI CAs) to patients. Typically, the contrast agents increase the signal of the diseased vs. healthy area and permit the radiologist to diagnose the patient properly. MRI CAs have been on the market since the 90's and all contain the rare metal gadolinium (Gd). Millions of patients have been given Gd-based contrast agents (GBCAs) without any serious side effects when following the prescribing information. Several hundred million MRI scans using GBCAs have been performed worldwide over the last years. In recent years, regulatory health authorities have however raised concerns about the use of GBCAs with reported retention of Gd in the brain and other tissues after administration. This concern is applicable for GE Healthcare's own GBCA and other competitor products. As a proactive response, GE Healthcare AS (GEHC), Norway started investigating the use of another class of MRI CAs based on the naturally occurring metal manganese (Mn). Early research and development have been promising and warrant further investigation in animals and humans. The main goal of the present BIA project has been to develop with international and renown R&D partners a novel manganese-based CA for general use, thereby establishing a new paradigm within the field of MRI CAs. With a successful BIA project, further clinical investigation and various commercialization activities will be undertaken prior to planned product launch. The market introduction of GEHC's novel manganese-based CA will address an unmet clinical need to the great satisfaction of physicians and patients. Since project start, March 1st, 2017, the research has focused on screening and selecting suitable candidates for further testing in animals. Multiple candidates have been synthesized and evaluated in terms of manufacturing ability, stability, biodistribution, safety and MRI contrast efficacy. A lead candidate with acceptable biological performance and MR contrast efficacy was chosen early 2020 and progressed to testing, including non-clinical safety in controlled GLP studies. The development has included extensive development of the active substance and drug product to support the GLP studies, including establishment of manufacturing processes, analytical methods for production and quality control. Production of drug product for stability testing has been set up in the GEHC manufacturing Plant at Storo, Oslo. The GEHC research lab at the Oslo Science Park has been upgraded with lab instruments and expertise personnel. These activities lay the ground for further non-clinical studies which will enable transition into the clinical development phase in close collaboration with the Oslo University Hospital. More scale up and optimization of processes, methods and product is needed for the clinical program. Manufacturing readiness at both our Norwegian manufacturing sites, Lindesnes Plant (drug substance) and Oslo Plant (drug product), will continue with a clear objective to develop sustainable manufacturing processes.

Based on support via the BIA program, GE has been able to develop a new manganese based contrast agent into pre-clinical phase.

GE Healthcare (GEHC) is one of the global leaders within medical imaging and contrast agents. Magnetic resonance imaging (MRI) is the fastest growing imaging modality with more than 35 million procedures being performed in 2015 using Contrast Agents (CAs). All marketed MRI CAs contain the rare earth metal gadolinium (Gd) and are considered to be very safe. In recent years, regulatory health authorities have however raised concerns about the use of Gd-based CAs (GBCAs) in patients with severe reduced kidney function, including GE Healthcare's own GBCA, Omniscan® and other competitor products. As a proactive reaction GEHC AS (Norway) has just started investigating the use of endogenous Mn as the MRI active moiety in a novel class of CAs. The project has a high risk profile. The potential value creation for GEHC is nevertheless high and the future product will fulfill an unmet clinical need within the field of MRI CAs. Early research on novel Mn-based CAs has been promising, thus warranting further preclinical and clinical investigation. The main project goal is to develop, with international and renown R&D partners, a novel Mn-based CA, thereby establishing a new paradigm within the field of MRI CAs. With a successful project, further clinical investigation and various commercialization activities will be undertaken prior to planned product launch.