West Coast Editor

Less than a month after a scientific paper showed that Advanced Magnetics Inc.'s intravenous iron replacement therapy boosts fertility, the company reported Phase III success with ferumoxytol in its targeted indication: chronic kidney disease (CKD) in patients not on dialysis.

The news on data presented at the American Society of Nephrology's Renal Week Annual Meeting in San Diego sent Advanced Magnetic's shares (NASDAQ:AMAG) up Friday almost 30 percent, or $13.10, to close at $57.

Enrolling 340 patients randomized to get either two 510-mg doses of ferumoxytol within one week or 200 mg of oral iron daily for three weeks, the study showed ferumoxytol beat oral iron to a statistically significant degree in all primary and secondary endpoints - and did so whether patients already were taking erythropoiesis-stimulating proteins (ESPs, such as Aranesp, Amgen Inc. and Procrit, Johnson & Johnson) or not.

The ESP factor is particularly important, because a recent study, which the New England Journal of Medicine published this week, found that high doses of ESPs might boost the risk of cardiac events.

"Concerns have been raised in the past about raising hemoglobins too quickly or taking them too high," said Lisa Gordon, vice president of business and strategy for Cambridge, Mass.-based Advanced Magnetics. "There's been talk about it."

The company plans to finish enrolling its final Phase III trial, which is testing ferumoxytol in dialysis-dependent CKD patients, by the end of next year's first quarter, and submit a new drug application during the second half of 2007. Along with a safety study, the Phase III program includes two trials with CKD patients not on dialysis and one with those undergoing dialysis.

"We're going for both," Gordon said. Most hemodialysis patients use erythropoietin, and chronic use of EPO requires supplements of intravenous iron, since oral iron is inadequate for replacing such stores. "It's kind of like the analogy of gas and engine," she said. "I.V. iron is the gas."

Ferumoxytol was designed to be given in large doses quickly, thanks to the compound's semi-synthetic carbohydrate coating. In the latest trial, patients tolerated ferumoxytol well with repeated dosing, and adverse events happened more often with oral iron patients (52 percent) than ferumoxytol patients (35.5 percent). Drug-related adverse events followed the trend, occurring in 24 percent of oral iron patients and 10.6 percent of those given ferumoxytol. Serious adverse events also took place more in the oral iron group (9.3 percent) than the ferumoxytol group (4.6 percent).

If approved, Advanced Magnetics' product will go up against Ferrlecit (sodium ferric gluconate, Watson Pharma Inc.) and Venofer (iron sucrose injection, American Regent Inc.) - both given during five-minute infusions, with Ferrlecit delivered in a 125-mg dose and Venofer at 100 mg. The 510-mg dose of ferumoxytol takes less than 20 seconds, and neither Ferrlecit nor Venofer is indicated for pre-dialysis patients.

Earlier this month, a study in Obstetrics & Gynecology found that certain forms of female infertility can be treated by iron supplementation with non-heme (not from blood) iron such as ferumoxytol. The nine-year study watched the pregnancy success rate in more than 18,000 pre-menopausal women with no history of infertility, and found that non-heme iron reduces the risk of developing ovulatory infertility by half (p<0.001).

In the latest Phase III CKD data in non-dialysis patients, efficacy results in the intent-to-treat (ITT) and efficacy-evaluable (EE) populations proved similar. Specifically, in the ITT population, ferumoxytol outperformed oral iron for the primary endpoint of change in hemoglobin at day 35 (ferumoxytol 0.81 +/- 1.24 g/dl vs. oral iron 0.21 +/- 1.04 g/dl, p=0.0002).

In the EE population at day 35, patients given ferumoxytol had a significantly greater mean increase in hemoglobin compared to patients in the oral iron group (ferumoxytol 0.86 +/- 1.23 g/dl vs. oral iron 0.06 +/- 1.08 g/dl, p<0.0001), and the intravenous supplement was more likely to increase baseline hemoglobin by greater than or equal to 1 g/dl compared to oral iron (ferumoxytol 42.3 percent vs. oral iron 16.1 percent, p=0.0004).

An increase in serum ferritin, the iron-storage protein, was significantly greater in the ferumoxytol group compared to the oral iron group at day 21 (ferumoxytol 551.0 +/- 301.7 ng/ml vs. oral iron 8.9 +/- 52.2 ng/ml, p<0.0001).

Researchers stratified the data by ESP use, and found a significant difference in hemoglobin increase for ferumoxytol compared to oral iron in both patients who were on ESPs and those who were not.

At day 35, the mean hemoglobin increase in the group on a stable ESP dose was 1.20 +/- 1.54 g/dl for ferumoxytol compared to -0.12 +/- 1.27 g/dl for oral iron (p=0.0015). In the group not on ESPs, the mean hemoglobin increase at day 35 was 0.70 +/- 1.01 g/dl for ferumoxytol compared to 0.15 +/- 0.99 g/dl for oral iron (p=0.0038). Using ESPs along with ferumoxytol resulted in 61 percent of patients achieving an increase in hemoglobin of at least 1 g/dl compared to 16.7 percent of patients on ESP and oral iron (p=0.001).