Advanced Magnetics Inc. reported positive data from the fourth and final Phase III trial of its intravenous iron replacement therapy, and plans to file a new drug application in the fourth quarter.

The study of ferumoxytol in 230 chronic kidney disease patients on hemodialysis showed statistically significant improvement vs. oral iron on the primary endpoint of increased hemoglobin levels.

Both secondary endpoints also were met with statistical significance.

Brian Pereira, president and CEO of the Cambridge, Mass.-based company, said Advanced Magnetics intends to seek approval for use of ferumoxytol in treating CKD patients, including those on dialysis and those who are not. It also would include patients who are or are not taking erythropoietin.

Its Phase III program that totaled more than 1,600 patients tested both groups of CKD patients.

"Assuming a timely review process and if all goes well, we hope we'll be on the market by early 2009;" Pereira told BioWorld Today. "We plan to commercialize it ourselves in the U.S. because commercializing in the kidney disease space requires a limited sales force. We think a 70-person sales force, plus sales and marketing infrastructure, should be more than adequate."

In the meantime, he said, Advanced Magnetics is evaluating options as far as commercializing ferumoxytol outside the U.S., and its options related to developing the product for additional indications - for example, for use in cancer patients or in those with heavy menstrual bleeding.

Pereira said there are 350,000 to 400,000 dialysis patients in the U.S. who require iron replacement therapy, and 750,000 to 1 million predialysis patients with that need.

The standard of care for dialysis patients now is the infused products Ferrlecit (sodium ferric gluconate, Watson Pharma Inc.) and Venofer (iron sucrose injection, American Regent Inc.). The standard of care for nondialysis patients is oral iron.

Advanced Magnetics already demonstrated superiority to oral iron, and Pereira said his product has several advantages vs. Ferrlecit and Venofer, delivered at 125 mg and 100 mg, respectively. First, he said, ferumoxytol is delivered in a higher dose, with two 510-mg doses constituting one treatment course. Second is that the ferumoxytol is delivered much quicker, in about 17 seconds vs. 15 minutes. And finally, ferumoxytol has the advantage of being injected rather than infused. Those benefits come from the nanoparticle-based iron product's semi-synthetic carbohydrate coating, low levels of catalytic free iron and its iso-osmolar formulation, Pereira said.

"We would price our drug at least equivalently to the current I.V. drugs and possibly at a premium," he said, indicating that would equate to about $370 per gram, or course, of ferumoxytol treatment.

The fourth Phase III trial was an open-label, randomized study in 230 CKD patients on hemodialysis who were receiving erythropoietin therapy, bringing to more than 1,600 the number of patients in the four-trial Phase III program.

For the primary endpoint of change in hemoglobin from baseline to day 35 after the first dose, ferumoxytol patients had a mean increase of 1.02 g/dL vs. 0.46 for oral iron (p=0.0002). For one secondary endpoint, a higher proportion of ferumoxytol-treated patients (49.1 percent) achieved at least a 1.0 g/dL rise in hemoglobin at day 35 compared to those taking oral iron (25 percent; p=0.0002). For the other secondary endpoint, the mean increase in serum ferritin from baseline was significantly greater in the ferumoxytol group than the oral iron group at day 21 (plus 356.7 ng/mL vs. minus 37.6; p<0.0001).

"We are very pleased with the results that we are releasing today from our fourth and final ferumoxytol Phase III study in CKD patients. We now have released data from all of our planned pivotal studies of ferumoxytol in CKD patients," Pereira said in a news release. "The consistent, statistically significant achievement of all primary and secondary endpoints across all trials and at all stages of CKD is important."

Safety data between ferumoxytol and oral iron appeared comparable, which is what the company was trying to show, or even better for the intravenous product.

Pereira said the company expects to provide updates later this year on potential new applications for ferumoxytol, as well as an update on its Combidex molecular imaging agent for detecting cancerous lymph nodes. Combidex was the subject of an FDA approvable letter in March 2005.

Advanced Magnetics reported $145.7 million in cash and investments as of March 31, and since then has raised $163 million in a public offering. It reported a net loss of $17.6 million for the first half of its year. Its stock (NASDAQ:AMAG), which was trading around $11 two years ago, closed Monday at $59.03, down $1.13.