Top-line data showing that ferric citrate, an iron-based drug sold by Keryx Biopharmaceuticals Inc., can help certain patients with chronic kidney disease (CKD) better deal with a common complication, iron deficiency anemia (IDA), positioned the company to seek an expanded label for the drug later this year. An approval in the indication could significantly boost revenue by expanding the market for the drug, analysts said.

Keryx plans to submit full data from the pivotal phase III study to the FDA in support of a supplemental new drug application for IDA in the third quarter.

The potential gains ahead cheered some Keryx investors, who have seen company shares (NASDAQ:KERX) fall 62.1 percent since a year ago amid slower-than anticipated adoption of the drug by kidney doctors and patients. By Tuesday's market close, they had lifted shares by 8.6 percent to $4.94.

"This trial is, clinically, tremendously important," Geoffrey Block, study co-chair and director of Clinical Research at Denver Nephrology, told BioWorld Today. "It shows that people who previously either couldn't get or didn't tolerate oral iron, when given ferric citrate, had a tremendous and sustained response in their hemoglobin."

IDA, which occurs when the body doesn't have enough iron to produce healthy red blood cells, is common in people with CKD. It can leave patients feeling weak, dizzy and with difficulties with concentration as well as frequent headaches and shortness of breath. In the U.S., about 1.6 million people are estimated to have both IDA and nondialysis dependent CKD. About 650,000 of those patients are currently receiving treatment for IDA from their nephrologists.

Ferric citrate, an oral, absorbable iron-based compound, first gained FDA approval as Auryxia in September 2014 for the control of serum phosphorus levels in patients with CKD on dialysis. Approvals followed in Japan and Europe. But with just $10.1 million in sales in 2015, it has fallen short of initial expectations. An approval in IDA could change that, potentially adding nearly $200 million in peak annual sales, according to J.P. Morgan analyst Whitney Ijem.

The phase III study that read out Tuesday compared treatment with ferric citrate to placebo in 234 patients who hadn't adequately responded to or tolerated other oral iron therapies. It met its primary endpoint, with 52 percent of patients who received ferric citrate achieving a 1g/dL or greater rise in hemoglobin at any time point during the 16-week randomized efficacy period, compared to 19 percent in the placebo group (p<0.001).

While lower degrees of increase in hemoglobin are still clinically significant, Block said, regulatory agencies view the 1g/dL threshold as being important from a drug development perspective. The actual rise in hemoglobin and its translation to how people feel varies among individuals and where someone starts, he said.

The trial also hit all of its secondary endpoints, with statistical significance including mean change in hemoglobin, mean change in transferrin saturation, mean change in ferritin, percent of patients with durable response and mean change in serum phosphate.

Two patients in the placebo group discontinued the study and were not included in the efficacy analysis. One quit after randomization prior to receiving placebo. Another quit after taking a dose of placebo but before having laboratory values drawn. Statistically significant differences in all prespecified secondary efficacy endpoints were also observed.

During the full 24 weeks of the study, ferric citrate was generally well tolerated. The majority of adverse events reported were mild to moderate, with the most common being diarrhea, constipation, discolored feces and nausea. During the efficacy period, 26 percent of ferric citrate-treated patients and 30 percent of those receiving placebo discontinued treatment. Of the patients who discontinued, 12 patients treated with ferric citrate discontinued due to an adverse event, compared to 10 patients who received placebo.

Full data from the study will be presented at a medical meeting during the fourth quarter, likely the American Society of Nephrology's Kidney Week in Chicago, said Ijem.

Despite the likelihood of Keryx getting approval for the label expansion, wrote Cowen and Co. analyst Boris Peaker, "commercial uptake and adoption remain uncertain." While the label expansion represents a market which is nearly double the size of Auryxia's current market in CKD dialysis patients, he pointed out, "in the near future we may see payer pushback given the lack of long-term outcome data for pre-dialysis treatment with a potent oral iron."

Ferric citrate has been the key focus at Keryx ever since the company's oral Akt inhibitor perifosine, then partnered with Canadian biotech Aeterna Zentaris Inc., failed to improve overall survival in a phase III colorectal cancer trial in 2012. (See BioWorld Today, April 3, 2012.)