Zemiva, a molecular imaging radiopharmaceutical, in combination with initial clinical information in patients suspected of acute coronary syndrome (ACS), resulted in significantly improved sensitivity compared to the sensitivity of the initial clinical diagnosis alone, while maintaining specificity, according to a Phase 2 trial sponsored by manufacturer Molecular Insight Pharmaceuticals.
The BP-23 trial was an open-label study of 342 patients at 50 hospitals throughout North America that enrolled emergency department patients with chest pain symptoms consistent with ACS, according to the Cambridge, Mass.-based company during a conference call in March.
Zemiva (iodofiltic acid I 123 or BMIPP) is a metabolic, molecular imaging pharmaceutical that has previously demonstrated the ability to detect cardiac ischemia up to 30 hours after an ischemic event as compared to currently available techniques, which are limited to an approximate two-hour imaging window.
Patients received a Zemiva scan within 30 hours of cessation of chest pain and prior to any intervention or provocative testing. Zemiva scans were not used to triage the patients.
Researchers found that the combination of Zemiva SPECT imaging with initial clinical information resulted in improved sensitivity (85 percent) that was statistically significant, compared to the sensitivity of the initial clinical diagnosis alone (52 percent). There was a slight increase in specificity for the diagnosis of cardiac ischemia, but the increase was not statistically significant.
The negative predictive value increased significantly to 90 percent for patients with cardiac ischemia when Zemiva was added, up from 72 percent with standard diagnostic techniques alone. In patients with a negative Zemiva scan, there were no hard cardiac events, including MIs or death from cardiac causes during the 30-day follow up, according to researchers.
“For the first time, we have an imaging agent in Zemiva that can give you an imprint of an antecedent ischemia for up to 30 hours after the ischemia actually happened. It’s the only tracer that can directly tie symptoms to true tissue ischemia,” said principal investigator James E. Udelson, MD, chief of the division of cardiology and director of nuclear cardiology at Tufts Medical Center, during the phone conference.
“The big advantage of Zemiva is that it removes the time factor. In other words, someone could have had ischemia eight hours ago, and if they did and if it affected the myocardial tissue, you should be able to see it with the Zemiva scan,” Udelson said. “Moreover, if their symptoms many hours earlier were not a consequence of ischemia, the scan should be normal. You can manage the patients appropriately even if they show up many hours after symptoms have resolved. And that is the big difference: there is no other imaging agent that can do that.”
The current trial is designed to be a pivotal registration trial that, upon replication in a successive confirmatory Phase 3 trial, could form the basis of an application with the FDA for marketing approval.
“With the successful BP-23 results, the Phase 2 clinical development requirements have been met and we will proceed to Phase 3,” said John W. Babich, PhD, CEO of Molecular Insight. “In recent discussions with the FDA to review these Phase 2 clinical development results and our proposal for Phase 3 clinical trial design, the agency indicated that a single Phase 3 trial, with robust results, would be sufficient to support Zemiva’s approval.” Babich expects the Phase 3 trial to begin in early 2010.
Udelson noted that Zemiva’s impact should be on decisions to hospitalize or discharge a chest pain patient. “I think the negative predictive value of it would be very important. If you could say with confidence that a patient hasn’t had an ischemic episode within the past 24 hours—after an hour or two of evaluation, it would make a big difference."