THERAPEUTIC PIPELINE

SNF472

Renal disease leads to a progressive loss of kidney function. In its last phase, called end-stage renal disease (ESRD), kidney failure is permanent and irreversible and the patient requires renal replacement therapy through dialysis or a renal transplant. ESRD is associated with significant morbidity, premature mortality, decreased quality of life, and increased health-care expenditures. The metabolic and hormonal abnormalities in ESRD lead to a chronic state of inflammation, malnutrition, disordered mineral metabolism, anemia, and electrolyte disturbances, all contributing to significant cardiovascular disease in this population. Calcium deposits form in the cardiovascular system of patients with ESRD, a process called cardiovascular calcification (CVC), which impairs the function of the cardiovascular system. Sanifit is developing SNF472 as a potential treatment for two indications related to cardiovascular calcification in patients with ESRD.

 

Indications

TREATMENT OF CALCIFIC UREMIC ARTERIOLOPATHY (CUA)

Calcific uremic arteriolopathy (CUA), also called calciphylaxis, is a severe form of cardiovascular calcification in which the calcium deposits block small blood vessels in skin and fat tissue. These blockages cause the development of intensely painful and debilitating chronic skin lesions. CUA is a devastating rare disease which affects up to 4% of dialysis patients and has a 1-year mortality rate of 55%. Wound-related infections and other complications are leading causes of morbidity and hospitalization in patients with CUA. Patients are usually treated with pain medications and wound management but there are no approved therapies to address the underlying cause of the disease. SNF472 inhibits pathological cardiovascular calcification and has the potential to offer an innovative solution for this devastating condition. Sanifit has obtained orphan drug status from the FDA and EMA for SNF472 as an investigational treatment for CUA. In an open-label phase 2 study in which SNF472 was administered for 12 weeks, statistically and clinically significant improvements from baseline were achieved across multiple measures of efficacy, including wound healing, pain, and quality of life. Sanifit has successfully completed end-of-phase 2 regulatory interactions with the FDA and EMA and preparations for a larger, placebo-controlled phase 3 study are underway.
 

CARDIOVASCULAR CALCIFICATION IN END-STAGE RENAL DISEASE

Most patients with ESRD do not develop CUA. However, CVC occurs at an accelerated rate in ESRD patients compared to patients with other chronic diseases and correlates with development of cardiac dysfunction and failure with an increased likelihood of arrhythmia and sudden cardiac death. The annual cardiovascular event rate in these patients is around 20% and approximately half of patients on hemodialysis die from cardiovascular causes.

No drugs are approved to treat CVC, thus there is an unmet need for a novel therapy to reduce the progression of CVC and lower the burden of morbidity and mortality in these patients. There are more than 3 million ESRD patients worldwide and approximately 70% of them are treated with dialysis (2.5 million). A therapy to directly treat CVC and reduce the rate of cardiovascular events would be a first-in-class drug with a market potential of over 2 billion.

SNF472 blocks the formation and growth of calcium crystals and Sanifit is conducting a phase 2 randomized, placebo-controlled study to assess the effect of SNF472 on progression of cardiovascular calcification in ESRD patients. This study, known as CaLIPSO, was initiated in 2017, with results expected by the end of 2019. For more information on the study refer to  clinicaltrials.gov/ct2/show/NCT02966028?term=sanifit&rank=1.

 

RELATED PUBLICATIONS

  • First-time-in-human randomized clinical trial in healthy volunteers and haemodialysis patients with SNF472, a novel inhibitor of vascular calcification (British J Clin Pharmacol 2018)
  • Phase 2 open label single arm repeat dose study to assess the effect of SNF472 on wound healing in uraemic calciphylaxis patients (Kidney Week 2017)
  • Charaterization of SNF472 pharmacokinetics and efficacy in uremic and nonuremic rat models of cardiovascular calcification (PLOS ONE 2017)
  • SNF472 can be administered during hemodialysis to attain potentially therapeutic phytate levels (J Nephrol 2017)
  • A novel pharmacodynamic assay to evaluate the effects of crystallization inhibitors on calcium phosphate crystallization in human plasma (Scientific Reports 2017)
  • Hypothesis: Phytate is an important unrecognized nutrient and potential intravenous drug for preventing vascular calcification (Medical Hypotheses 2016)

  • SNF472 inhibits vitamin D induced cardiovascular calcification in rats (Kidney Week 2013)