ECR presentation sets stage for FDA submissionThe long-awaited next generation of blood pool agents for MR imaging has taken a step closer to reality. German researchers reported positive results at the European Congress of
ECR presentation sets stage for FDA submission
The long-awaited next generation of blood pool agents for MR imaging has taken a step closer to reality. German researchers reported positive results at the European Congress of Radiology regarding the phase III clinical trials of MS-325, a blood pool agent with staying power far beyond that of the contrast agents now in use.
Trial results, reported March 7 in Vienna, demonstrated a mean accuracy of 84% for MR angiograms enhanced by MS-325, when compared with x-ray angiography. MR without enhancement achieved a mean accuracy of 72%. Adverse events among the 178 patients with suspected peripheral vascular disease were mostly mild and transient, typically involving tingling, itching, and nausea.
Comparing MS-325 images with unenhanced 2D time-of-flight images, the post-MS-325 images display five to six times the signal-to-noise and contrast-to-noise ratio, according to Epix Medical, the developer of the agent. This allows for visualization of a broader range of arterial structures and for improved steady-state imaging. Clinical studies with MS-325 demonstrate that mean arterial signal to noise and contrast to noise drop by only 10% between five and 50 minutes after injection of the agent.
Data reported at the ECR indicate that MS-325 significantly increases the number of images that can be clinically interpreted. Fewer than 1.7% of all vessels on MS-325-enhanced MR angiograms were uninterpretable in the study, whereas 17% of the vessels on noncontrast MRA and approximately 2.8% of the vessels on x-ray angiograms were uninterpretable, according to Dr. Mathias Goyen of the MR Center at the University Hospital in Essen, Germany, who presented the latest results at the ECR.
The findings come as no big surprise to the imaging community, which had been apprised of similar results achieved in earlier phase II and phase III clinical studies of MS-325. It now appears, however, that Epix is getting close to submitting applications to both the FDA and European authorities.
In a telephone conference held the morning the ECR results were presented, Epix Medical CEO Michael D. Webb predicted the company would submit a new drug application to the FDA later this year. The NDA submission will include results from four phase III MS-325 clinical trials in patients with suspected vascular disease in the aortoiliac, pedal, and renal arteries.
Toward this end, two studies, including the one presented at the ECR, have been completed. Enrollment has been completed in the two remaining phase III clinical trials for the detection of vascular disease in the pedal and renal arteries, and the data are being read and analyzed. The company expects to release results of those studies in the summer of 2003.
"As soon as the results of the renal and pedal trials are known, we will be able to finalize our NDA submission timeline," Webb said. "We are targeting submission for this fall."
An application to market MS-325 in Europe will follow the FDA submission, he said. Schering of Germany holds exclusive worldwide sales and marketing rights to MS-325.
Researchers have been studying widely varying areas of the body to support a broad indication for MS-325, according to Webb. The work-in-progress medium persists longer in the bloodstream than conventional MR contrast media because it binds to serum albumin. Conventional media open an imaging window for only about three minutes, with optimal enhancement only in the first minute. They require relatively large doses and generally do a poor job of vessel enhancement, according to the ECR presentation.
"One injection of MS-325 lights up the entire vascular system from head to toe for an hour," Webb said. "Clinicians can view the entire vascular system, looking for vascular narrowing in a comprehensive and systemic way."