Lantheus Holdings, Inc. (NASDAQ: LNTH), the parent company of Lantheus Medical Imaging, Inc. (“LMI”), a global leader in the development, manufacture and commercialization of innovative diagnostic imaging agents, today announced positive new data from a Phase 2 study of LMI 1195, a fluorine-18 (F18) labeled tracer for use in cardiac positron emission tomography (PET) to assess myocardial presynaptic sympathetic nerve function. Altered sympathetic nervous system (SNS) function has been implicated in a broad range of clinical conditions including heart failure and sudden death. The data was presented during a poster presentation at the American College of Cardiology’s 67th Annual Scientific Session (ACC.18) on Monday, March 12, 2018 at 9:45 a.m. ET in the Noninvasive Imaging Moderated Poster Theater.
The data show that PET imaging with LMI 1195 provides a comparable measure of cardiac sympathetic nerve function and more favorable kinetics for early cardiac imaging as PET imaging with carbon-11 (C11) hydroxyephedrine (HED). C11 HED has been used in cardiac PET imaging to characterize SNS integrity and risk-stratify patients with ischemic cardiomyopathy considered for implantable cardiac defibrillators (ICD). However, widespread clinical utility is limited due to the short half-life of C11-labeled tracers, which require the onsite availability of a cyclotron.
Rob Beanlands, M.D., Head, Division of Cardiology, University of Ottawa Heart Institute and an investigator in the study commented, “The Phase 2 study findings are encouraging and show the comparability of PET imaging with LMI 1195 and C11 HED in a variety of relevant cardiac conditions, including patients with ischemic cardiomyopathy at risk for sudden cardiac arrest. He added, “The PAREPET study conducted at the University of Buffalo has previously indicated that PET C11 HED imaging may provide additional information useful for the risk stratification of patients considered for ICD placement. Our initial findings suggesting the comparability of LMI 1195 and C11 HED are important. A new, widely available non-invasive tool that could lead to a more precise selection of patients prior to ICD implantation would be a very welcome addition to the currently available, but limited armamentarium.”
Nine participants were enrolled in the study. Participants (n=2 healthy controls; n=6 ischemic cardiomyopathy patients with left ventricular (LV) ejection fraction (EF) =34±4; and n=1 non-ischemic cardiomyopathy patient with EF=37%) underwent two separate PET imaging visits within one week. On the first visit, participants underwent N13 ammonia and dynamic HED PET imaging. On the second visit, participants underwent dynamic LMI 1195 PET imaging. The order of testing was randomized. HED and LMI 1195 retention index (RI) was quantified to assess presynaptic sympathetic nerve function. LV, lung, liver and blood standardized uptake values were also determined at different time intervals.
The findings suggest that LMI 1195 yields a comparable estimate of cardiac sympathetic innervation as C11 HED. LMI 1195 retention index (r=0.89, p<0.0001) and defect score (r-0.99, p<0.0001) correlated highly with HED. LV-to-lung ratios were comparable between the two tracers. In addition, LMI 1195 seems to offer more favorable kinetics for early cardiac imaging than HED. A significant difference in blood clearance was observed between the two tracers resulting in a LV-to-blood ratio of LMI-1195 higher than HED within the first five minutes following administration (p<0.05).
Cesare Orlandi, M.D., Chief Medical Officer of Lantheus Medical Imaging added, “We believe LMI 1195 may represent a first-in-class agent and useful diagnostic tool for a significant population of patients at risk for sudden cardiac death. Nuclear imaging provides a unique tool to measure the molecular changes in the heart, including cardiac function of the norepinephrine transporter (NET), in a non-invasive and repeatable manner. Lantheus developed LMI 1195 to target the NET and we are encouraged by these initial results that have been obtained in a variety of clinical conditions. Data from this and other collaborations with academic centers in Canada and Europe have allowed us to progress the LMI 1195 program to this stage and have provided the basis for the initiation of a Phase 3 trial in ischemic cardiomyopathy patients scheduled to receive an ICD. We look forward to initiating this pivotal study later in the year.”