Drug could treat IDA in patients with NDD CKD

Prescription drugs
Photo courtesy of CDC

Results of a phase 3 trial suggest oral ferric citrate could be an alternative to intravenous iron for treating iron deficiency anemia (IDA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD).

Slightly more than half of patients receiving ferric citrate in this study experienced a significant boost in hemoglobin levels.

A treatment effect was seen as early as 1 to 2 weeks after patients started ferric citrate, and responses were durable.

Patients enrolled in the trial had not adequately responded to or could not tolerate prior treatment with oral iron.

Ferric citrate was generally well tolerated in this trial. Adverse events (AEs) were consistent with the drug’s known safety profile, with diarrhea being reported as the most common AE.

These results were published in the Journal of the American Society of Nephrology. The study was sponsored by Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate as Auryxia.

The drug is currently approved in the US as a phosphate binder for the control of serum phosphorus levels in patients with CKD who are on dialysis.

Researchers conducted this phase 3 trial to determine if ferric citrate might be a safe and effective alternative to intravenous iron in patients with NDD CKD.

The study enrolled NDD-CKD patients with hemoglobin levels between 9.0 g/dL and 11.5 g/dL who were intolerant to or had inadequate response to oral iron supplements.

The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=116). Baseline characteristics were similar between the treatment arms.

The study had a 16-week, double-blind efficacy period, followed by an 8-week, open-label, safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate.

During the 16-week efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day with food and could be titrated every 4 weeks by an additional 3 tablets for up to 12 tablets per day. The mean dose received in ferric citrate-treated patients was 5 tablets per day.

Efficacy

The study’s primary endpoint was the proportion of patients achieving a ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period.
 
A significantly higher proportion of patients in the ferric citrate arm achieved the primary endpoint—52.1%, compared to 19.1% of patients receiving placebo (P<0.001).

The mean relative change in hemoglobin (for ferric citrate vs placebo) at week 16 was 0.84 g/dL (P<0.001).

Patients who received ferric citrate were significantly more likely to experience a sustained increase in hemoglobin—48.7%, compared to 14.8% for those receiving placebo (P<0.001).

“Not only did ferric citrate deliver a clinically meaningful 1 g/dL increase in hemoglobin levels for the majority of patients . . ., increases were seen as early as 1 to 2 weeks after start of treatment and were sustained for the majority of patients who achieved the primary endpoint,” said study author Steven Fishbane, MD, of Hofstra Northwell School of Medicine in Mineola, New York.

Safety

Treatment-emergent AEs occurred in 79.5% of patients in the ferric citrate arm and 64.7% of those in the placebo arm.

Common AEs (in the ferric citrate and placebo arms, respectively) included diarrhea (20.5% and 16.4%), constipation (18.8% and 12.9%), discolored feces (14.5% and 0%), nausea (11.1% and 2.6%), abdominal pain (6% and 1.7%), fatigue (0% and 5.2%), hyperkalemia (6.8% and 3.4%), and hypertension (4.3% and 5.2%).

Rates of serious AE were similar in the ferric citrate and placebo arms—12.0% and 11.2%, respectively. None of the serious AEs were considered treatment-related.

There were 2 deaths in the ferric citrate arm (and none in the placebo arm), but neither were considered treatment-related.

“The results shown in this pivotal study demonstrated that ferric citrate, if approved for this indication, could provide an important new treatment option for people living with chronic kidney disease and iron deficiency anemia who are not on dialysis,” Dr Fishbane said.

Keryx Biopharmaceuticals recently submitted a supplemental new drug application with these data to the US Food and Drug Administration.

Prescription drugs
Photo courtesy of CDC

Results of a phase 3 trial suggest oral ferric citrate could be an alternative to intravenous iron for treating iron deficiency anemia (IDA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD).

Slightly more than half of patients receiving ferric citrate in this study experienced a significant boost in hemoglobin levels.

A treatment effect was seen as early as 1 to 2 weeks after patients started ferric citrate, and responses were durable.

Patients enrolled in the trial had not adequately responded to or could not tolerate prior treatment with oral iron.

Ferric citrate was generally well tolerated in this trial. Adverse events (AEs) were consistent with the drug’s known safety profile, with diarrhea being reported as the most common AE.

These results were published in the Journal of the American Society of Nephrology. The study was sponsored by Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate as Auryxia.

The drug is currently approved in the US as a phosphate binder for the control of serum phosphorus levels in patients with CKD who are on dialysis.

Researchers conducted this phase 3 trial to determine if ferric citrate might be a safe and effective alternative to intravenous iron in patients with NDD CKD.

The study enrolled NDD-CKD patients with hemoglobin levels between 9.0 g/dL and 11.5 g/dL who were intolerant to or had inadequate response to oral iron supplements.

The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=116). Baseline characteristics were similar between the treatment arms.

The study had a 16-week, double-blind efficacy period, followed by an 8-week, open-label, safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate.

During the 16-week efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day with food and could be titrated every 4 weeks by an additional 3 tablets for up to 12 tablets per day. The mean dose received in ferric citrate-treated patients was 5 tablets per day.

Efficacy

The study’s primary endpoint was the proportion of patients achieving a ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period.
 
A significantly higher proportion of patients in the ferric citrate arm achieved the primary endpoint—52.1%, compared to 19.1% of patients receiving placebo (P<0.001).

The mean relative change in hemoglobin (for ferric citrate vs placebo) at week 16 was 0.84 g/dL (P<0.001).

Patients who received ferric citrate were significantly more likely to experience a sustained increase in hemoglobin—48.7%, compared to 14.8% for those receiving placebo (P<0.001).

“Not only did ferric citrate deliver a clinically meaningful 1 g/dL increase in hemoglobin levels for the majority of patients . . ., increases were seen as early as 1 to 2 weeks after start of treatment and were sustained for the majority of patients who achieved the primary endpoint,” said study author Steven Fishbane, MD, of Hofstra Northwell School of Medicine in Mineola, New York.

Safety

Treatment-emergent AEs occurred in 79.5% of patients in the ferric citrate arm and 64.7% of those in the placebo arm.

Common AEs (in the ferric citrate and placebo arms, respectively) included diarrhea (20.5% and 16.4%), constipation (18.8% and 12.9%), discolored feces (14.5% and 0%), nausea (11.1% and 2.6%), abdominal pain (6% and 1.7%), fatigue (0% and 5.2%), hyperkalemia (6.8% and 3.4%), and hypertension (4.3% and 5.2%).

Rates of serious AE were similar in the ferric citrate and placebo arms—12.0% and 11.2%, respectively. None of the serious AEs were considered treatment-related.

There were 2 deaths in the ferric citrate arm (and none in the placebo arm), but neither were considered treatment-related.

“The results shown in this pivotal study demonstrated that ferric citrate, if approved for this indication, could provide an important new treatment option for people living with chronic kidney disease and iron deficiency anemia who are not on dialysis,” Dr Fishbane said.

Keryx Biopharmaceuticals recently submitted a supplemental new drug application with these data to the US Food and Drug Administration.

Prescription drugs
Photo courtesy of CDC

Results of a phase 3 trial suggest oral ferric citrate could be an alternative to intravenous iron for treating iron deficiency anemia (IDA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD).

Slightly more than half of patients receiving ferric citrate in this study experienced a significant boost in hemoglobin levels.

A treatment effect was seen as early as 1 to 2 weeks after patients started ferric citrate, and responses were durable.

Patients enrolled in the trial had not adequately responded to or could not tolerate prior treatment with oral iron.

Ferric citrate was generally well tolerated in this trial. Adverse events (AEs) were consistent with the drug’s known safety profile, with diarrhea being reported as the most common AE.

These results were published in the Journal of the American Society of Nephrology. The study was sponsored by Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate as Auryxia.

The drug is currently approved in the US as a phosphate binder for the control of serum phosphorus levels in patients with CKD who are on dialysis.

Researchers conducted this phase 3 trial to determine if ferric citrate might be a safe and effective alternative to intravenous iron in patients with NDD CKD.

The study enrolled NDD-CKD patients with hemoglobin levels between 9.0 g/dL and 11.5 g/dL who were intolerant to or had inadequate response to oral iron supplements.

The patients were randomized 1:1 to receive ferric citrate (n=117) or placebo (n=116). Baseline characteristics were similar between the treatment arms.

The study had a 16-week, double-blind efficacy period, followed by an 8-week, open-label, safety extension period in which all patients remaining in the study, including the placebo group, received ferric citrate.

During the 16-week efficacy period, ferric citrate was administered at a starting dose of 3 tablets per day with food and could be titrated every 4 weeks by an additional 3 tablets for up to 12 tablets per day. The mean dose received in ferric citrate-treated patients was 5 tablets per day.

Efficacy

The study’s primary endpoint was the proportion of patients achieving a ≥1 g/dL increase in hemoglobin at any point during the 16-week efficacy period.
 
A significantly higher proportion of patients in the ferric citrate arm achieved the primary endpoint—52.1%, compared to 19.1% of patients receiving placebo (P<0.001).

The mean relative change in hemoglobin (for ferric citrate vs placebo) at week 16 was 0.84 g/dL (P<0.001).

Patients who received ferric citrate were significantly more likely to experience a sustained increase in hemoglobin—48.7%, compared to 14.8% for those receiving placebo (P<0.001).

“Not only did ferric citrate deliver a clinically meaningful 1 g/dL increase in hemoglobin levels for the majority of patients . . ., increases were seen as early as 1 to 2 weeks after start of treatment and were sustained for the majority of patients who achieved the primary endpoint,” said study author Steven Fishbane, MD, of Hofstra Northwell School of Medicine in Mineola, New York.

Safety

Treatment-emergent AEs occurred in 79.5% of patients in the ferric citrate arm and 64.7% of those in the placebo arm.

Common AEs (in the ferric citrate and placebo arms, respectively) included diarrhea (20.5% and 16.4%), constipation (18.8% and 12.9%), discolored feces (14.5% and 0%), nausea (11.1% and 2.6%), abdominal pain (6% and 1.7%), fatigue (0% and 5.2%), hyperkalemia (6.8% and 3.4%), and hypertension (4.3% and 5.2%).

Rates of serious AE were similar in the ferric citrate and placebo arms—12.0% and 11.2%, respectively. None of the serious AEs were considered treatment-related.

There were 2 deaths in the ferric citrate arm (and none in the placebo arm), but neither were considered treatment-related.

“The results shown in this pivotal study demonstrated that ferric citrate, if approved for this indication, could provide an important new treatment option for people living with chronic kidney disease and iron deficiency anemia who are not on dialysis,” Dr Fishbane said.

Keryx Biopharmaceuticals recently submitted a supplemental new drug application with these data to the US Food and Drug Administration.