hexasodium phytate (SNF472) / CSL Behring - LARVOL DELTA

Comparative efficacy of interventions for vascular calcification and stiffness in dialysis patients:a systematic review and network meta-analysis. (PubMed, Cardiorenal Med) - "This study suggests that SUCRA rankings indicate STS has a potential comprehensive advantage in improving vascular stiffness and delaying calcification progression, making it a reasonable exploratory choice for dialysis patients with concurrent VC and VS. While EA ranks highest in SUCRA for reducing CAC volume score, it has limited impact on VS and requires caution regarding long-term safety. Given the limited sample size, network sparsity for some outcomes, and mostly non-significant between-group comparisons, large-scale, head-to-head RCTs are needed to further validate these findings."

Journal • Retrospective data • Review • Cardiovascular

Novel Mechanisms and Emerging Therapeutic Strategies in Vascular Calcification. (PubMed, Eur J Pharmacol) - "Examples of such agents include SNF472 and ataciguat. Finally, we address key translational challenges and propose future directions for developing effective, multi-targeted interventions."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Targeted Protein Degradation

Microcalcification: Effects on Atherosclerotic Vulnerable Plaques, Detection, and Therapeutic Perspectives. (PubMed, Curr Atheroscler Rep) - "Among them, ¹⁸F-NaF PET/CT has been used as a biomarker for microcalcification activity and is capable of identifying high-risk plaques. Drugs targeting hydroxyapatite nucleation, such as SNF472 and bisphosphonates, have made considerable progress in the treatment of vascular calcification, yet further clinical translational trials are still needed to verify their efficacy."

Journal • Review • Atherosclerosis • Cardiovascular

Uremic Toxin-Driven Vascular Calcification in Chronic Kidney Disease: Molecular Pathways and Integrated Phenotypes. (PubMed, Toxins (Basel)) - "This phenotype-oriented paradigm transforms VC from an inevitable complication into a targetable and potentially reversible manifestation of uremic toxicity, establishing a translational foundation for precision-based vascular medicine in chronic kidney disease. The framework enables biomarker-guided patient stratification, rational therapeutic selection, and phenotype-enriched clinical trial design."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease • FGF23 • NLRP3

Targeting Vascular Calcification: Novel Insights into Molecular Pathways and Clinical Interventions. (PubMed, Cardiovasc Drugs Ther) - "Recent studies have highlighted several breakthrough approaches: nanotechnology-based delivery systems, optimized agents such as SNF472 and GLP-1 receptor agonists, and bioactive constituents from traditional Chinese medicine (e.g., ginsenosides, chelerythrine), all of which target distinct calcification pathways...Progress in multi-omics technologies continues to uncover new molecular mechanisms and therapeutic targets, guiding precision medicine. By integrating mechanistic insights with novel therapeutic paradigms, this review aims to facilitate the development of personalized management strategies and ultimately improve cardiovascular outcomes in high-risk populations."

Journal • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Diabetes • Endocrine Disorders • Metabolic Disorders • Nephrology • Renal Disease

Calciphylaxis diagnosis, management and future directions: a comprehensive update on behalf of the European Renal Association CKD-MBD Working Group. (PubMed, Clin Kidney J) - "Recent investigational therapies, including SNF472 and INZ-701, target key calcification pathways and offer promise. Looking ahead, future research should prioritize the development and validation of diagnostic criteria, and prognostic tools integrating clinical risk factors with biomarkers. In addition, we propose the routine inclusion of patient-reported experience measures in calciphylaxis studies to better capture treatment impact in this vulnerable population."

Journal • Review • Calciphylaxis • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Inflammation • Pain • Rare Diseases • Renal Disease • Thrombosis • MGP

Cardiovascular Safety of Hexasodium Phytate (SNF472) in Patients with CKD on Hemodialysis: A Systematic Review and Meta-Analysis (KIDNEY WEEK 2025) - "Conclusion SNF472 demonstrates a favorable cardiovascular safety profile and shows promising efficacy in enhancing wound healing and alleviating pain in patients with CKD. However, additional clinical trials with expanded patient populations are needed to further clarify its long-term safety and therapeutic benefit in this high-risk population."

Retrospective data • Review • Calciphylaxis • Cardiovascular • Chronic Kidney Disease • Nephrology • Rare Diseases • Renal Disease

Establishment of a medial arterial calcification model in C57BL/6J mice via arterial intimal injury. (PubMed, Cardiovasc Diagn Ther) - "Calcifcation inhibitors etidronate and SNF472 significantly prevented MAC occurrence, showing inhibition rates of 45.45% (P=0.006) and 50% (P=0.002), respectively, conpared to the VD3 group (Fisher's exact test). This study not only establishes a MAC animal model by inducing injury to the CCA combined with a VD3 diet but also introduces a corresponding pathological scoring system. Together, this model, coupled with this associated grading method, provides a valuable toolset for future basic medical research, drug screening, and investigations into the genetic mechanisms of MAC."

Journal • Preclinical • Cardiovascular • CD68 • CD86 • IL1B • IL6

Hexasodium Fytate (SNF472 or CSL525) Inhibits Ectopic Calcification in Various Pseudoxanthoma Elasticum and Calcinosis Cutis Animal Models. (PubMed, Pharmaceuticals (Basel)) - "CSL525 inhibited skin calcification development by 60% in the calcinosis cutis rat model. CSL525 may prove beneficial not only in preventing the progression of cardiovascular calcification but also in treating other ectopic calcification conditions, including skin calcification associated with genetic disorders such as PXE."

Journal • Preclinical • Calciphylaxis • Cardiovascular • Genetic Disorders • Metabolic Disorders • Rare Diseases • ABCC6

REDUCTION OF CALCIPHYLAXIS-RELATED INFECTIONS WITH HEXASODIUM FYTATE TREATMENT IN A RANDOMIZED, DOUBLE-BLIND, PHASE 3, PLACEBO-CONTROLLED TRIAL (ISN-WCN 2025) - "Introduction CALCIPHYX was an international, phase 3, randomized, double-blind, placebo-controlled clinical trial that investigated hexasodium fytate (SNF472), an inhibitor of vascular calcification, for the treatment of calciphylaxis...Download: Download high-res image (82KB) Download: Download full-size image Conclusions In this exploratory analysis, hexasodium fytate treatment during hemodialysis reduced the incidence of first and multiple calciphylaxis-related infections. This abstract was also submitted for the American Society of Nephrology Kidney Week 2024 congress."

Clinical • P3 data • Calciphylaxis • Infectious Disease • Nephrology • Pain • Rare Diseases

Reduction of Calciphylaxis-Related Infections with Hexasodium Fytate Treatment in a Randomized, Double-Blind, Phase 3, Placebo-Controlled Trial (KIDNEY WEEK 2024) - "Time to first calciphylaxis-related infection Background: CALCIPHYX was an international, phase 3, randomized, double-blind, placebo-controlled clinical trial that investigated hexasodium fytate (SNF472), an inhibitor of vascular calcification, for the treatment of calciphylaxis... In this exploratory analysis, hexasodium fytate treatment during hemodialysis reduced the incidence of first and multiple calciphylaxis-related infections."

Clinical • P3 data • Calciphylaxis • Infectious Disease • Pain • Rare Diseases

Inositol Hexaphosphate in Bone Health and Disease. (PubMed, Biomolecules) - "SNF472, hexasodium IP6, is currently being evaluated in clinical studies as a treatment for vascular calcification and calciphylaxis. However, since HA crystal growth within bone matrix is an essential process in bone formation, it is possible that IP6 intake may inhibit physiological mineralization and bone formation, although currently more published studies suggest that IP6 may contribute to bone health rather than inhibit bone formation. Given that IP6 and its metabolites are thought to have diverse activities and many health benefits, it remains important to consider the range of effects of IP6 on bone."

Journal • Review • Calciphylaxis • Oncology • Rare Diseases

Hexasodium fytate for the treatment of calciphylaxis: a randomised, double-blind, phase 3, placebo-controlled trial with an open-label extension. (PubMed, EClinicalMedicine) - P3 | "In patients with calciphylaxis, BWAT-CUA and Pain VAS improved similarly in hexasodium fytate- and placebo-treated patients; over the course of the entire trial, there were fewer deaths and calciphylaxis-related events leading to hospitalisation in the hexasodium fytate group. Funded by Sanifit, a CSL Vifor company."

Journal • P3 data • Calciphylaxis • Pain • Rare Diseases

SNF472: a novel therapeutic agent for vascular calcification and calciphylaxis. (PubMed, J Nephrol) - "The efficacy and safety of SNF472 in inhibiting vascular calcification have been confirmed in recent clinical studies. This review summarizes the results of studies related to SNF472 to provide a comprehensive overview of its mechanism of action, efficacy, safety, and ongoing clinical studies."

Journal • Review • Calciphylaxis • Cardiovascular • Chronic Kidney Disease • Nephrology • Rare Diseases • Renal Disease

Hexasodium fytate exposure-response correlations in a randomized, placebo-controlled study of patients on dialysis with cardiovascular calcification. (PubMed, Front Pharmacol) - P2 | "In the CaLIPSO study, infusion of hexasodium fytate (SNF472), the hexasodium salt of inositol hexaphosphate, for 52 weeks thrice weekly during hemodialysis significantly reduced progression of coronary artery calcification (CAC)...Simple Emax models show robust relations among exposure, inhibition of hydroxyapatite crystallization, and change in CAC volume. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier NCT02966028."

Journal • Cardiovascular

Calciphyx: Phase 3 Study of SNF472 for Calciphylaxis (clinicaltrials.gov) - P3 | N=71 | Completed | Sponsor: Sanifit Therapeutics S. A. | Active, not recruiting ➔ Completed

Trial completion • Calciphylaxis • Rare Diseases

Cardiovascular calcifications in dialysis patients (PubMed, Nephrol Ther) - "The prevention and treatment of cardiovascular calcifications go through the correction of classic risk factors associated with atherosclerosis, mineral and bone metabolism disorders and by optimizing the dose and the efficiency of dialysis. New therapeutic strategies are beginning to emerge, others are being evaluated, such as sodium thiosulfate, rheopheresis, vitamin K, magnesium supplementation, and SNF-472."

Journal • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Metabolic Disorders • Nephrology • Renal Disease

Hexasodium Fytate (SNF472) for Treatment of Calciphylaxis (KIDNEY WEEK 2023) - "CALCIPHYX did not meet either alternate primary efficacy outcome. BWAT-CUA and Pain VAS improved similarly in both groups. There were numerically fewer AEs leading to death and CUA-wound related events and infections in patients treated with SNF472 compared to placebo."

Late-breaking abstract • Calciphylaxis • Infectious Disease • Pain • Rare Diseases

Cardiovascular calcifications in dialysis patients (PubMed, Nephrol Ther) - "The prevention and treatment of cardiovascular calcifications go through the correction of classic risk factors associated with atherosclerosis, mineral and bone metabolism disorders and by optimizing the dose and the efficiency of dialysis. New therapeutic strategies are beginning to emerge, others are being evaluated, such as sodium thiosulfate, rheopheresis, vitamin K, magnesium supplementation, and SNF-472."

Journal • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Metabolic Disorders • Nephrology • Renal Disease

Future treatment of vascular calcification in chronic kidney disease. (PubMed, Expert Opin Pharmacother) - "In this review we examined the literature and summarized the pathophysiology, biomarkers and focused on the treatments of VC. Even though there is no consensus regarding specific treatment options, we provide the currently available treatment strategies that focus on phosphate balance, correction of vitamin D and vitamin K deficiencies, avoidance of both extremes of bone turnover, normalizing calcium levels and reduction of inflammatory response and the potential and promising therapeutic approaches liketargeting cellular mechanisms of calcification (e.g. SNF472, TNAP inhibitors).Creating novel scores to detect in advance VC and implementing targeted therapies is crucial to treat them and improve the future management of these patients."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Inflammation • Nephrology • Renal Disease

Hemodialysis complications: focus on pruritus and vascular calcifications (PubMed, Nephrol Ther) - "It includes the use of skin emollients, optimization of dialysis parameters and management of chronic kidney disease complications, and specifically the use of difelikefalin. Although recommended, this screening is rarely performed in dialysis centers. Prevention and treatment against the development of cardiovascular calcifications are the control of risk factors associated with atherosclerosis, control of phosphatemia, and new therapeutic strategies such as sodium thiosulfate, rheopheresis, vitamin K, magnesium supplementation or SNF-472, a calcium chelator currently in clinical development."

Journal • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dermatology • Dyslipidemia • Nephrology • Pain • Pruritus • Renal Disease

Hemodialysis complications: focus on pruritus and vascular calcifications (PubMed, Nephrol Ther) - "It includes the use of skin emollients, optimization of dialysis parameters and management of chronic kidney disease complications, and specifically the use of difelikefalin. Although recommended, this screening is rarely performed in dialysis centers. Prevention and treatment against the development of cardiovascular calcifications are the control of risk factors associated with atherosclerosis, control of phosphatemia, and new therapeutic strategies such as sodium thiosulfate, rheopheresis, vitamin K, magnesium supplementation or SNF-472, a calcium chelator currently in clinical development."

Journal • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dermatology • Dyslipidemia • Nephrology • Pain • Pruritus • Renal Disease

Calciphyx: Phase 3 Study of SNF472 for Calciphylaxis (clinicaltrials.gov) - P3 | N=66 | Active, not recruiting | Sponsor: Sanifit Therapeutics S. A. | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2022 ➔ Dec 2022 | Trial primary completion date: Mar 2022 ➔ Oct 2022

Enrollment closed • Trial completion date • Trial primary completion date • Calciphylaxis • Rare Diseases

Interventions to Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials. (PubMed, J Am Soc Nephrol) - "Mixed results were reported for single studies of exercise, vitamin E-coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal. Conclusions Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

Role of Myoinositol Hexaphosphate (SNF 472) in Calciphylaxis: an update. (PubMed, Ther Apher Dial) - No abstract available

Journal • Calciphylaxis • Rare Diseases