Delving into the Latest Updates on Bixalomer with Synapse

Background: Hyperphosphatemia is associated with cardiovascular morbidity and mortality in adults with chronic kidney disease (CKD). Drug therapy has an irreplaceable role in the management of hyperphosphatemia. Objectives: We aimed to compare and rank phosphorus-lowering drugs, including phosphate binder and nonphosphate binder, in hyperphosphatemia adults with CKD. Methods: We did a systematic review and frequentist random-effect network meta-analysis. We searched in PubMed, Cochrane Library, Web of Science, and Embase from inception to February 1, 2023, for randomized controlled trials of 12 phosphorus-lowering drugs in adults with hyperphosphatemia and CKD. Primary outcomes were efficacy (changes in serum phosphorus) and acceptability (treatment withdrawals due to any cause). We ranked each drug according to the value of surface under the cumulative ranking curve. We applied the Confidence in Network Meta-Analysis frameworks to rate the certainty of evidence. This study was registered with PROSPERO, number CRD42022322270. Results: We identified 2,174 citations, and of these, we included 94 trials comprising 14,459 participants and comparing 13 drugs or placebo. In terms of efficacy, except for niacinamide, all drugs lowered the level of serum phosphorus compared with placebo, with mean difference ranging between −1.61 (95% credible interval [CrI], −2.60 to −0.62) mg/dL for magnesium carbonate and −0.85 (−1.66 to −0.05) mg/dL for bixalomer. Only ferric citrate with odds ratios 0.56 (95% CrI: 0.36–0.89) was significantly associated with fewer dropouts for acceptability. Of the 94 trials, 43 (46%), 7 (7%), and 44 (47%) trials were rated as high, moderate, and low risk of bias, respectively, the certainty of the evidence was moderate to very low. Conclusions: Magnesium carbonate has the best phosphorus-lowering effect in hyperphosphatemia adults with CKD; considering efficacy and acceptability, ferric citrate shows evidence to be the most appropriate drug with or without dialysis.

03 Jul 2022·Expert Opinion on Drug SafetyQ3 · MEDICINE

An update on phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a review of safety profiles

Q3 · MEDICINE

Review

Author: Ogata, Hiroaki ; Takeshima, Akiko ; Ito, Hidetoshi

INTRODUCTIONHyperphosphatemia is an inevitable complication for patients undergoing dialysis, as is the resulting need for treatment with phosphate binders. Currently, various phosphate binders are clinically available. In addition to their phosphate-lowering activity, individual phosphate binders have differing safety profiles and off-target actions.AREAS COVEREDThis paper reviews the safety of phosphate binders and issues to be resolved.EXPERT OPINIONCalcium-based phosphate binders are well tolerated but may increase calcium overload risk. Sevelamer reduces serum cholesterol levels and exerts anti-inflammatory effects. Compared to sevelamer, bixalomer is associated with fewer gastrointestinal symptoms. Aluminum-containing binders, lanthanum carbonate, and sucroferric oxyhydroxide exhibit strong phosphate-lowering activity. Although ferric citrate reduces erythropoiesis-stimulating agents and intravenous iron doses, its use requires monitoring of iron metabolic markers to avoid overload. Occasionally, combined use of multiple phosphate binders can offer the advantages of each phosphate binder while minimizing their drawbacks; thus, this may be desirable according to individual patients' conditions and comorbidities. However, increased pill burden and nonadherence to phosphate binders emerge as new problems. We expect that novel therapeutic strategies will be developed to resolve these issues.

01 Nov 2021·Mini-Reviews in Medicinal ChemistryQ3 · MEDICINE

The Rising Risk of Chronic Kidney Disease (CKD) and How it is Dealt with: A Review of Current and Potential Phosphate Binders (PB)

Q3 · MEDICINE

Review

Author: Danel, Krzysztof ; Gosik, Robert

:It is estimated that by 2040, Chronic Kidney Disease (CKD) will be the 5th main cause of global deaths. It has been suggested that hyperphosphatemia is among the main factors leading to the increased risk of death. This review focuses on potential and currently used Phosphate Binders (PB). Aluminum hydroxide is presently not recommended due to potential aluminum toxicity. Calciumcontaining phosphate binders (CCPB) can cause calcium overload, resulting in hypercalcemia and an increased risk of cardiovascular diseases. Magnesium and calcium complexes were suggested to be as effective as sevelamer in the reduction of serum phosphate, with the potential to slow down the process of calcification. However, limited studies have been conducted in this area. Although sevelamer seemed to have a positive influence on cardiovascular calcification and arterial stiffness, its influence on mortality was unclear. Sevelamer crystal accumulation in the Gastrointestinal tract (GI) can cause gastrointestinal bleeding. Lanthanum carbonate seemed to lower all-cause mortality and reduce the chance of hypercalcemia, even though a deposit in the GI tract was observed. Colestilan, like sevelamer, reduced LDL cholesterol. Sucroferric oxyhydroxide had a lower pill burden than other PBs and it seemed to reduce serum FGF-23. Ferric citrate improved parameters that are related to anemia but can cause iron overload. Bixalomer appeared to have fewer gastrointestinal side effects than sevelamer. Nano-lanthanum hydroxide and SBR759 may have an interesting future as PBs. In conclusion, the development of new PBs should also take into consideration their potential to function as protection modifiers.

100 Deals associated with Bixalomer

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KEGG	Wiki	ATC	Drug Bank
D09586	-	B	DB15200

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hyperphosphatemia	JP	Astellas Pharma, Inc.	30 Mar 2012

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Kidney Diseases	Discovery	JP	Astellas Pharma, Inc.	01 Jan 2010
Uremia	Discovery	JP	Astellas Pharma, Inc.	01 May 2009
Kidney Failure, Chronic	Discovery	-	Amgen, Inc.	01 Mar 2008
Tumoral Calcinosis, Hyperphosphatemic, Familial	Discovery	-	Amgen, Inc.	01 Mar 2008
Hyperphosphatemia	Discovery	US	Ilypsa, Inc.	01 Jun 2006

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Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01742611 (Pubmed) Manual	Phase 3	Hyperphosphatemia \| Chronic Kidney Diseases	105	Bixalomer	(epqtvaeiex) = cejaywjkdc egdcbrwhdr (wmltxkgito ) View more	Positive	01 Apr 2017
NCT00505037 (Pubmed \| Ther Apher Dial)	Phase 2	Chronic Kidney Diseases	156	Bixalomer 1.5g/day	ntncxmohnp(fzyyuehkfd) = rxsvjvoepg mptditybou (znogbtrlvy )	-	01 Jun 2014
				Bixalomer 3.0g/day	ntncxmohnp(fzyyuehkfd) = ytxselggfk mptditybou (znogbtrlvy )
ASN2013	Not Applicable	-	114	Bixalomer	useoezxxjt(mfmttblhzq) = irgycaykdt fqpoaqtdua (lkkdhwqodx ) View more	Positive	05 Nov 2013
				Sevelamer hydrochloride	useoezxxjt(mfmttblhzq) = resflibhrc fqpoaqtdua (lkkdhwqodx ) View more