FDA advisory panel does not recommend the agency approve binodenoson

Modifications in the original study endpoints were cited among the chief concerns.

The pharmacologic stress agent binodenoson was not recommended for approval by the FDA.

The Cardiovascular and Renal Drugs Advisory Committee voted 11 to 5 not to recommend the new drug application of binodenoson 250 mg (CorVue, King Pharmaceuticals) for approval by the FDA. The drug is proposed as a vasodilator in myocardial perfusion imaging in patients with suspected coronary artery disease. In three double-blind, phase III trials evaluating the efficacy of the drug (referred to as studies 301, 302 and 305), researchers reported that the studies failed to meet their original primary endpoints. Patients enrolled in studies 301 (n=357) and 302 (n=419) were randomly assigned to receive either adenosine or biodenoson with myocardial perfusion imaging using the 17-segment model of the heart. Patients in study 305 (n=433) were randomly assigned to receive either adenosine or biodenoson for myocardial perfusion imaging in various combinations and sequences.

The researchers originally defined success in the study as the concordance of results from myocardial perfusion imaging tests as measured by the lower limit of the 95% confidence interval for the kappa statistic exceeding 0.61. According to data published in the FDA briefing, the lower limits of the kappa statistic were 0.15 for study 301, 0.27 for study 302 and 0.36 for study 305. Following modifications of the success criteria, which required that the 95% confidence interval of the mean difference scores fall between the interval of –1.5 and 1.5 and that the upper limit of the 95% confidence interval in patients with extreme discordance be less than 10%, the researchers reported that all three studies met the conditions.

“I voted no because I felt there was additional data that needed to be collected, and that what was presented was still insufficient to convince me that the drug was equivalent to adenosine at this point,” Peter Conti, MD, PhD, a professor of radiology at the University of Southern California Keck School of Medicine, said during the panel vote.

Despite the majority of votes not to recommend approval, several panel members felt that the data presented were adequate, despite concerns over the altered endpoints and efficacy of the drug.

“I voted yes,” Mori J. Krantz, MD, an associate professor of medicine at the University of Colorado and director of the CV Prevention and Electrocardiogram Core Lab at the Colorado Prevention Center in Denver, said in his explanation. “Although there certainly were a lot of limitations in the database that we addressed, in my gut and my clinical gestalt, there is moderate discernment of ischemic burden with this agent, and further studies looking particularly at prior coronary arteriography are warranted.” – by Eric Raible