hexasodium phytate (SNF472) / CSL Behring - LARVOL DELTA

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

[VIRTUAL] Walking Performance, Quality of Life, and Hemodynamic Characteristics in Patients with Peripheral Artery Disease and End-Stage Kidney Disease (PAD-ESKD) (AHA 2021) - "We demonstrate the high prevalence of impaired walking ability in patients with PAD-ESKD, a previously poorly characterized population. The PAD-ESKD population has high clinical need, supporting a planned randomized, placebo-controlled trial to evaluate the effects of SNF472, a novel investigational inhibitor of vascular calcification."

Clinical • HEOR • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Peripheral Arterial Disease • Renal Disease

The CALCIPHYX study: a randomized, double-blind, placebo-controlled, Phase 3 clinical trial of SNF472 for the treatment of calciphylaxis. (PubMed, Clin Kidney J) - "This randomized, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing."

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

[VIRTUAL] A Case of Severe Penile Pain (KIDNEY WEEK 2021) - "Since starting HD 1 year prior, his serum phosphorous ranged 7.8-9.0mg/dL, Ca 8.0-9.0mg/dL and parathyroid hormone downtrended from 611 to 127pg/mL on hectorol, phoslo and Ca carbonate...Treatment goals included phosphate normalization by 4 weekly HD sessions, low Ca dialysate, non Ca based phosphate binders; vasodilators sildenafil and pentoxifylline, and sodium thiosulphate (blocks calcification of smooth muscle cells). He is in a clinical trial for SNF472, a selective calcification inhibitor, for wound healing and pain management...It is essential that we identify penile calciphylaxis, given its significant morbidity and mortality. Penile calciphylaxis"

Clinical • Atherosclerosis • Calciphylaxis • Cardiovascular • Chronic Kidney Disease • Dermatology • Diabetes • Diabetic Nephropathy • Dyslipidemia • Endocrine Disorders • Hematological Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Pain • Peripheral Arterial Disease • Rare Diseases • Renal Disease • Secondary Hyperparathyroidism • Thrombosis • Transplantation • Urology

[VIRTUAL] Assessment of Vascular Calcification Using Micro-CT Quantification in a Vitamin D Rat Model (KIDNEY WEEK 2021) - "Three of the rats were subcutaneously treated with 60 mg/kg SNF472 (G1), an inhibitor of calcification, and the rest were treated with saline (G2)...A significant correlation was obtained between the calcium deposits quantified by micro-CT and the total calcium quantified by ICP-AES. Conclusion The threshold-based quantification method by micro-CT can be a useful and reliable tool to evaluate vascular calcification and the efficacy of inhibitors of vascular calcification in rat models, especially in large-diameter vessels such as aorta."

Preclinical

[VIRTUAL] SNF472 ATTENUATES THE PROGRESSION OF FEMORAL ARTERY CALCIFICATION AND RECOVERS LIMB BLOOD PERFUSION AND WALKING ABILITY IN A RAT MODEL OF PERIPHERAL ARTERY DISEASE (ERA-EDTA 2021) - "For example, cilostazol is approved for PAD but its use is limited in PAD-ESKD patients. SNF472 attenuates the progression of vascular calcification and improves blood perfusion and the functional parameters MWT and MWD in a rat model of PAD vascular calcification. These results support investigation of SNF472 as a potential therapy for PAD-ESKD patients who have vascular dysfunction due to a high degree of arterial calcification."

Preclinical • Cardiovascular • Chronic Kidney Disease • Nephrology • Peripheral Arterial Disease • Renal Disease

SNF472: mechanism of action and results from clinical trials. (PubMed, Curr Opin Nephrol Hypertens) - "Therapeutic agents that directly target VC may prevent the multiple complications associated with dystrophic calcification in patients with ESKD."

Clinical • Journal • Cardiovascular • Chronic Kidney Disease • Immunology • Inflammation • Nephrology • Renal Disease

Development of the BWAT-CUA Scale to Assess Wounds in Patients with Calciphylaxis. (PubMed, Diagnostics (Basel)) - "BWAT-CUA is a primary endpoint in an ongoing randomized, placebo-controlled phase 3 study of SNF472 recruiting patients with end-stage kidney disease and at least one ulcerated calciphylaxis lesion. BWAT-CUA, a newly developed tool for assessment of calciphylaxis wound severity and improvements over time, may be used in clinical research and in clinical practice."

Clinical • Journal • Calciphylaxis • Chronic Kidney Disease • Nephrology • Rare Diseases • Renal Disease

Effects of Myo-inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving Hemodialysis: An Analysis of the Randomized, Placebo-Controlled CaLIPSO Study. (PubMed, Clin J Am Soc Nephrol) - P2 | "Bone mineral density decreased modestly in all groups over 1 year. In the 600 mg SNF472 group, the reduction appeared more pronounced. Reported fractures were infrequent in all groups."

Clinical • Journal • Cardiovascular • Chronic Kidney Disease • Musculoskeletal Diseases • Nephrology • Orthopedics • Renal Disease

A Novel Ex Vivo Model of Aortic Valve Calcification. A Preliminary Report. (PubMed, Front Pharmacol) - "To block calcification, the inhibitor SNF472 (a formulation of the hexasodium salt of myo-inositol hexaphosphate hexasodium salt) was used at concentrations between 1 and 100 µM... A model of experimentally induced calcification in cultured whole leaflets from porcine aortic valves was developed. This model can be useful for studying the basic mechanisms of valve calcification and to test pharmacological approaches to inhibit calcification."

Journal • Preclinical