TOWARDS COMMERCIALIZATION OF T1p MRI FOR OSTEOARTHRITIS (OA) DIAGNOSIS AND TREATMENT MONITORING

AbstractOsteoarthritis (OA) is a debilitating disease that results in cartilage loss and pain, and has a significant impact on morbidity and healthcare costs worldwide. There is an unmet need for a therapeutic intervention that limits the progression of OA. Many therapeutic targets are being pursued by pharmaceutical companies to develop successful disease modifying therapy for OA. However, the major impediment in the development of effective OA therapeutics is the absence of a reliable index for measuring disease modifying effects of drug candidates in clinical trials.Radiographic measures of Joint Space Narrowing (JSN), currently used endpoints in clinical trials, lack sensitivity to soft tissues and thus are unable to detect early cartilage abnormalities. Thus, JSN may not be clinically relevant as a primary endpoint for measuring efficacy of a disease modifying agent. Therefore, there is a critical need for a validated noninvasive imaging biomarker for the early diagnosis of OA and to measure the response of a drug to develop novel therapeutics to improve OA patient care and reduce healthcare costs.A T1r MRI method, developed and patented by Dr. Reddy’s group at the University of Pennsylvania, has been shown to detect early cartilage abnormalities in OA patients including the finding that T1ρ values are elevated in early, moderate and advanced stages of OA (in a limited number of patients), when compared with corresponding asymptomatic subjects. However, for 3D T1r MRI to be a viable commercial product for routine clinical applications, one needs to address the following two challenges: i) the variability of 3D T1r MRI across MRI vendors; and II) the lack of validation of the 3D T1r MRI imaging biomarker.We propose to develop a robust clinically validated commercial 3D T1r MRI product for routine clinical diagnosis of OA and for measuring the progression of the disease and its response to therapy in OA clinical trials. Towards that goal, we propose to address the first challenge of commercialization by establishing the clinically relevant reproducibility error in T1ρ in healthy volunteers within and across 3T MRI scanners to generate an evidence-based foundation to move to Phase II for clinical validation of the biomarker. Once the variability of 3D T1r MRI has been established at the end of the proposed study, we will engage, in Phase II, to clinically validate 3D T1r MRI imaging biomarker using the standard of practice of OA disease diagnosis and progression, Kellgren-Lawrence (KL) grade (a gold standard), in a well powered clinical study. In addition, we will initiate collaborative OA clinical trials with Pharma/CRO during Phase II and will begin discussions with regulatory agencies to secure a CPT code for 3D T1r MRI for early diagnosis of OA.  Project Narrative  Osteoarthritis (OA) results in cartilage loss and pain and has significant impact in morbidity and healthcare  costs worldwide. Our goal is to develop a MRI-­based product to detect early changes in articular cartilage and  to establish this method as a quantitative and noninvasive biomarker for OA diagnosis and treatment monitoring  in clinical trials.