The iron-based phosphate binder PA21 has potent phosphate binding capacity and minimal iron release across a physiological pH range in vitro

Wilhelm, Maria; Gaillard, Sylvain; Rakov, Viatcheslav; Funk, Felix

doi:10.5414/cn108119

Cited by 48 publications

(39 citation statements)

References 23 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Phosphate binding occurs across a wide range of stomach pH, with a peak at pH 2.5. 40 Common adverse effects include diarrhoea and change in stool colour. There was no evidence of iron accumulation in a phase III extension study.…”

Section: Sucroferric Oxyhydroxidementioning

confidence: 99%

Phosphate binders in patients with chronic kidney disease

Chan¹,

Au²,

Francis³

et al. 2017

Aust Prescr

View full text Add to dashboard Cite

Section: Sucroferric Oxyhydroxidementioning

confidence: 99%

Phosphate binders in patients with chronic kidney disease

Chan¹,

Au²,

Francis³

et al. 2017

Aust Prescr

View full text Add to dashboard Cite

“…Sucroferric oxyhydroxide (SFOH; VELPHORO®; previously known as PA21) is a novel, iron-based phosphate binder that has been shown in vitro to have a high phosphate-binding capacity and low iron release [8]. In an open-label, randomized, Phase 3, 24-week study, SFOH demonstrated similar efficacy and tolerability to SEV carbonate (Renvela®) but with a lower pill burden [9].…”

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients

Sprague

Covic²,

Floege³

et al. 2016

Am J Nephrol

View full text Add to dashboard Cite

Background: Many patients with chronic kidney disease are prescribed vitamin D receptor agonists (VDRAs) for the management of secondary hyperparathyroidism. Oral phosphate binders may interact with, and potentially reduce the therapeutic activity of, oral VDRAs. This post hoc analysis of a Phase 3 study evaluated the pharmacodynamic effects of the iron-based phosphate binder sucroferric oxyhydroxide (SFOH) and sevelamer (SEV) carbonate on VDRA activity in dialysis patients. Methods: One thousand and fifty nine patients were randomized to SFOH 1.0-3.0 g/day (n = 710) or SEV 2.4-14.4 g/day (n = 349) for up to 52 weeks. Potential interactions of SFOH and SEV with VDRAs were assessed using serum intact parathyroid hormone (iPTH) concentrations as a pharmacodynamic biomarker. Three populations of SFOH- and SEV-treated patients were analyzed: Population 1 (n = 187), patients taking concomitant stable doses of oral VDRAs only; Population 2 (n = 250), patients taking no concomitant VDRAs; Population 3 (n = 68), patients taking concomitant stable doses of intravenous paricalcitol only. Populations were compared using a mixed-effects model to obtain the least squares mean change in iPTH from baseline to Week 52. Differences between treatment groups were also compared. Results: In Population 1, iPTH decreased from baseline to Week 52 in the SFOH group (-25.3 pg/ml) but increased in the SEV group (89.8 pg/ml) (p = 0.02). In Population 2, iPTH increased to a similar extent in both treatment groups. In Population 3, iPTH concentrations in both treatment groups decreased to a similar degree (-29.6 and -11.4 pg/ml for SFOH and SEV, respectively; p = 0.87). Conclusions: In contrast with SEV, SFOH did not appear to impact the iPTH-lowering effect of oral VDRAs.

show abstract

“…49 Under experimental conditions reproducing administration of the drug on an empty stomach and full stomach across the physiological pH range, sucroferric oxyhydroxide demonstrated to efficiently bind phosphate at every pH value and release more iron at the lowest pH in the absence of phosphate, whereas the amount of iron freed resulted in being much lower when phosphate was present and minimal with pH ranging from 2.5 to 8.5. 45 In more detail, in vitro experiments showed that iron release was equal to 0.3% at higher pH values while it amounted to a maximum of 6.3% at a pH of 1.2-1.5; the last percentage went up to 67% using an artificial gastric juice without phosphate. 49 It follows that iron uptake is greater in the fasting state and that, consequently, sucroferric oxyhydroxide must be taken with food.…”

mentioning

confidence: 99%

Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide

Cernaro

Santoro

Lacquaniti

et al. 2016

IJNRD

View full text Add to dashboard Cite

Chronic kidney disease-mineral bone disorder is frequent in patients with renal failure. It is characterized by abnormalities in mineral and bone metabolism with resulting hyperphosphatemia, low serum vitamin D, secondary hyperparathyroidism, altered bone morphology and strength, higher risk of bone fractures, and development of vascular or other soft tissue calcifications. Besides the recommendation to reduce phosphorus dietary intake, many drugs are currently available for the treatment of calcium/phosphate imbalance. Among them, phosphate binders represent a milestone. Calcium-based binders (calcium carbonate, calcium acetate) are effective in lowering serum phosphate, but their use has been associated with an increased risk of hypercalcemia and calcifications. Calcium-free binders (sevelamer hydrochloride, sevelamer carbonate, and lanthanum carbonate) are equally or slightly less effective than calcium-containing compounds. They would not induce an increase in calcium levels but may have relevant side effects, including gastrointestinal symptoms for sevelamer and risk of tissue accumulation for lanthanum. Accordingly, new phosphate binders are under investigation and some of them have already been approved. A promising option is sucroferric oxyhydroxide (Velphoro ® , PA21), an iron-based phosphate binder consisting of a mixture of polynuclear iron(III)-oxyhydroxide, sucrose, and starches. The present review is focused on pharmacology, mode of action, and pharmacokinetics of sucroferric oxyhydroxide, with a discussion on comparative efficacy, safety, and tolerability studies of this drug in chronic kidney disease and patient perspectives such as quality of life, satisfaction, and acceptability. Sucroferric oxyhydroxide has proven to be as effective as sevelamer in reducing phosphatemia with a similar safety profile and lower pill burden. Experimental and clinical studies have documented a minimal percentage of iron absorption without inducing toxicity. In conclusion, the overall benefit-risk balance of sucroferric oxyhydroxide is deemed to be positive, and this new drug may therefore represent a good alternative to traditional phosphate binders for the treatment of hyperphosphatemia in dialysis patients.

show abstract

The iron-based phosphate binder PA21 has potent phosphate binding capacity and minimal iron release across a physiological pH range in vitro

Abstract: These studies demonstrate that PA21 has potent phosphate binding capacity and low iron release over a physiologically relevant pH range in the GI tract. These features indicate PA21 could be an effective alternative phosphate binder for CKD patients.

Cited by 48 publications

References 23 publications

Phosphate binders in patients with chronic kidney disease

Phosphate binders in patients with chronic kidney disease

Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients

Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide

Contact Info

Product

Resources

About