Studies have shown that low levels of antibodies to phosphorylcholine (anti-PC) can indicate a higher risk for development of CVD as well as complications in existing patients. Therefore, the EU initiative CVDIMMUNE developed the candidate drug PC-mAb, an innovative fully human monoclonal antibody that can block vascular inflammation. The EU-funded project CARDIMMUN was established to pursue the scientific findings of CVDIMMUNE and put the candidate drug PC-mAb through clinical development and market registration. The overall goal was to ensure that PC-mAb reaches a commercially viable stage by demonstrating proof of activity in patients, and providing the necessary documentation to enter a clinical phase 2a (proof-of-concept) trial. To achieve these objectives, project partners conducted a number of supporting activities. These activities included preclinical disease models for demonstrating the efficacy of PC-mAb, allowing translation from preclinical models to secondary prevention in CVD patients. The good safety profile of PC-mAb was also demonstrated in toxicity studies and in pharmacokinetic profiles, supporting once monthly dosing of PC-mAb in phase 1 clinical studies in healthy volunteers and target patients. Occlusive arterial disease is a chronic disease in which the risk for severe events like heart attack and stroke is high. When occurring in the limb of a patient it severely restricts the mobility of the patients and therefore, their quality of life, causing extensive pain even when resting, as well as a high risk for amputation of the affected limbs. Results from this study in severe peripheral artery disease (PAD) patients undergoing revascularisation were positive; showing good safety and tolerability, as well as antibody properties supporting once monthly dosing. This formed the basis for generation of proof of activity data in a selected target patient group. CARDIMMUN has greatly increased the business attractiveness and value of the PC-mAb candidate drug, thereby securing plans to initiate a next proof-of-concept study.
Cardiovascular disease, PC-mAb, monoclonal antibody, CARDIMMUN, peripheral artery disease