LMI 1195 (CNA)
A PET agent designed to assess heart failure patients at risk of sudden cardiac death
LMI 1195 is an investigational fluorine-18-based positron emission tomography (PET) radiopharmaceutical imaging agent designed for molecular imaging of the norepinephrine pathway. As a novel small molecule tracer, LMI 1195 may be a useful tool in the diagnostic assessment and risk stratification of ischemic heart failure patients at risk of sudden cardiac death.
Potential tool to identify appropriate ICD implantation:
Heart failure is associated with changes in the cardiac sympathetic nerve function leading to an increased risk of sudden cardiac death. To prevent fatal arrhythmic events, implantable cardioverter defibrillators (ICDs) are implanted in heart failure patients meeting specific criteria. However, currently available tools to identify the most appropriate population for ICD implantation have limited predictive value, and only a small percentage of patients currently benefits from the procedure. We believe that a test that would identify a subset of patients at very low risk of sudden cardiac death would lead to improved targeted utilization of the devices and reduce the physical and financial consequences of inappropriate implantation.
LMI 1195 developed to target the NET:
The cardiac neuronal norepinephrine transporter, or NET, has been shown to be a useful target for the non-invasive monitoring of the cardiac sympathetic status and the assessment of the likelihood of a heart failure patient to develop fatal arrhythmias. Nuclear cardiac imaging provides a unique tool to measure the molecular changes in the heart, including cardiac function of NET, in a noninvasive and repeatable manner. We developed LMI 1195 to target the NET and are encouraged by initial clinical data.
Clinical Data and Next Steps
Phase 1 study results show that LMI 1195 has favorable safety, dosimetry and tolerability profiles. In addition, LMI 1195 provided high-quality, well-defined three-dimensional images of the autonomic nervous system of the heart. The data also showed that myocardial uptake of LMI 1195 was high and uniform throughout the heart and the radiotracer cleared quickly from the blood.
Collaborations with academic centers in the U.S., Canada and Europe have yielded clinical data that have been deemed adequate by the FDA to support advancing into a single Phase 3 clinical trial for an NDA submission. We are currently in discussions with authorities on the study design as well as the future reimbursement environment. This program would target patients with ischemic heart failure that are scheduled to undergo ICD implantation because of their risk of sudden cardiac death and would be designed to demonstrate that LMI 1195 improves the risk stratification of these patients.
Additionally, ongoing academic collaborations focusing on establishing the potential use of LMI 1195 for the diagnosis and treatment follow-up of neuroendocrine tumors, such as pheochromocytomas and paragangliomas, have also produced initial proof of concept data that is being pursued further for possible clinical development.