TREATMENT OF CALCIPHYLAXIS (ORPHAN) AND CARDIOVASCULAR DISEASE ESRD-HAEMODIALYSIS
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. The patient requires renal replacement therapy through dialysis or a renal transplant. The etiology of ESRD is heterogeneous but the main causes of renal failure are diabetes and hypertension. There are more than 3 million ESRD patients worldwide; around 70% of them are treated with dialysis (2.5 million). ESRD patients suffer from accelerated cardiovascular calcification, which correlates with higher cardiovascular risk. The annual death rate in ESRD ranges between 20-30% and the annual cardiovascular event rate is around 20%. Half of the deaths in dialysis are due to cardiovascular causes. Currently, no drugs are approved for this condition; patients are treated with calcimimetics and phosphate binders to control related risk factors such as hypercalcaemia and hyperphosphataemia. A therapy to directly treat cardiovascular disease in ESRD and reduce the rate of cardiovascular events would be a first-in-class drug which would fulfil an unmet medical need with a market potential of over €2Bn ($2.25Bn).
Calcific Uremic Arteriolopathy (CUA), also called calciphylaxis, represents the most severe form of cardiovascular calcification. CUA is a devastating rare disease which affects up to 4% of dialysis patients. It starts with a calcification of small peripheral vessels that quickly spreads. This represents the most severe form of cardiovascular calcification in dialysis patients. The natural course of the disease leads to painful necrotic skin ulcers as a consequence of the vascular calcification process. The disease has a 1-year mortality rate of 55% and an overall mortality of about 80%. There are no therapies approved for this indication. Patients are usually treated with intensive care, including aggressive wound management and off-label therapies. Calciphylaxis is a dramatic life-threatening condition which urgently requires new and effective treatments.
SNF472 is an intravenous formulation with a novel mechanism of action for haemodialysis patients with cardiovascular diseases linked to calcification. SNF472 is being developed for the two previously described indications: reduction of cardiovascular events in dialysis patients and for the treatment of calciphylaxis. SNF472 has orphan drug status for the treatment of calciphylaxis from both the EMA and FDA. SNF472 selectively blocks the pathological cardiovascular calcification progression and offers an innovative solution for these unmet medical needs. The intravenous route is promising for dialysis patients as it assures close to 100% compliance.
Sanifit has completed phase Ia studies with healthy volunteers and a phase Ib/IIa study in haemodialysis patients. From 2016, Sanifit will start a phase IIb study in ESRD and extend the orphan program in calciphylaxis into phase II/III clinical trials.
Additional formulations for a wider patient population (earlier Chronic Kidney Disease stages) and additional indications are under development.
Fore more information on our ongoing clinical trials, please click on the links below:
- SNF472 inhibits vitamin D induced cardiovascular calcification in rats (Kidney Week 2013)
- Progression of coronary artery calcification and cardiac events (Kidney Int 2011)
- Total and individual coronary artery calcium scores as independent predictors of mortality in hemodialysis patients (Am J Nephrol 2010)
- Coronary calcium as a predictor of coronary events in four racial or ethnic groups (N Eng J Med 2008)
- Phytate (Myo-inositol hexaphosphate) inhibits cardiovascular calcifications in rats (Front Biosci 2006)
- Effect of Crystallization Inhibitors on Vascular Calcifications Induced by Vitamin D (Circ J 2007)