BERLEX' ULTRAVIST CONTRAST AGENT RECOMMENDED FOR APPROVAL

BERLEX' ULTRAVIST CONTRAST AGENT RECOMMENDED FOR APPROVAL by FDA's medical imaging drugs advisory committee at its May 27 meeting. The committee voted unanimously that Berlex provided evidence showing that Ultravist (iopromide) injection is effective for: intra-arterial digital subtraction angiography (150 mg iodine/ml); peripheral venography (240 mgI/ml); cerebral arteriography, peripheral arteriography, contrast enhanced computed tomographic imaging of the head and body and excretory urography (300 mgI/ml); and coronary arteriography, left ventriculography, aortography and visceral angiography (370 mgI/ml). Ultravist, a nonionic low osmolar contrast agent, currently is marketed in 59 countries, including Germany, Sweden, and the U.K. Hans Peter Niendorf, MD, head of clinical development for diagnostics at Schering AG, told the committee that "postmarketing surveillance reflects a safety profile for Ultravist, which is very similar to that of Omnipaque and Isovue," contrast agents marketed by Sanofi Winthrop and Squibb Diagnostic, respectively. A "total of 65 clinical trials has been conducted outside of the United States, involving more than 10,000 adult and pediatric patients," Niendorf told the committee. Of these studies, 51 were submitted in the new drug application for Ultravist, which was filed March 2, 1992. Niendorf noted that 14 trials were completed after the NDA was filed. Berlex Labs Executive Director Clinical R&D Diagnostic Imaging Harold Goldstein, MD, described clinical trials conducted in the U.S. and U.K. Ultravist had 19 Phase II and Phase III studies, 15 of which were conducted in the U.S. and four in the U.K. All but one of the trials were double-blind with an active control. Seven Phase II trials involved 400 patients, 211 of whom received Ultravist. The other patients received standard low osmolar monomers. All 12 Phase III trials were conducted in the U.S. The active controls were Omnipaque, Isovue and Mallinckrodt's Optiray. "Each indication was supported by two or more studies generally involving 160 to 200 patients with 80 to 100 patients receiving Ultravist," Goldstein said. Efficacy data was presented by Burton Drayer, MD, director of magnetic resonance imaging and research, Barrow Neurological Institute, Phoenix, Arizona. The efficacy parameter used was the quality of the images, which was evaluated on a scale ranging from zero to three (not adequate to good). "In the aortography and visceral angiography study in which a 370 mg iodine dose was used...we can see that visualization was excellent in both groups [Ultravist v. pooled comparators]," Drayer said. "The mean contrast score...was similar and...a radiologic diagnosis could be made in both groups." The scores were 2.63 for Ultravist and 2.61 for the comparators. The mean contrast scores for Ultravist also were similar or higher than the pooled scores of the comparator agents for the other indications.