Emerging treatments

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Chronisch nierlijden (multidisciplinaire aanpak)Published by: WORELLast published: 2017GPC pluridisciplinaire sur la néphropathie chronique (IRC)Published by: Groupe de travail Développement de recommandations de première ligneLast published: 2017

Vadadustat

Vadadustat is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase. In phase 3 trials of patients with chronic kidney disease (CKD) (not undergoing dialysis and undergoing dialysis) and anaemia, vadadustat was non-inferior to darbepoetin alfa for change in the haemoglobin level from baseline and haemoglobin maintenance, and major cardiovascular adverse events.[174]​ The most common adverse reactions were hypertension and diarrhoea. Pooled results from two phase 3 trials in patients with non-dialysis-dependent CKD showed that vadadustat was non-inferior to darbepoetin alfa for haematological efficacy, but did not meet non-inferiority criterion for cardiovascular safety (a composite of death from any cause, non-fatal myocardial infarction, or non-fatal stroke).[175]​ Increased risk of thrombotic vascular events, including major adverse cardiovascular events, has been reported. Vadadustat is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of anaemia caused by CKD in adults who have been receiving dialysis for at least 3 months. It is only approved for patients who are on dialysis. UK guidelines recommend vadadustat as an alternative option to erythropoiesis-stimulating agents for symptomatic anaemia in CKD in patients who are on dialysis.[150][176][177]​​​​​

Roxadustat

Roxadustat is an oral inhibitor of HIF prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. Roxadustat may potentially serve as an alternative to erythropoiesis-stimulating agents for the management of anaemia in patients with CKD.[178][179]​​​[180][181][182][183]​​​​​​​​ The EMA has approved the use of roxadustat for the treatment of adults with symptomatic anaemia associated with CKD. The FDA has requested further trials on the safety of roxadustat in both non-dialysis-dependent and dialysis-dependent patient populations. UK guidelines recommend roxadustat as an alternative option to erythropoiesis-stimulating agents for symptomatic anaemia in CKD in patients who are not on dialysis at the start of treatment.[150][184]

Tenapanor

Tenapanor is a first-in-class sodium/hydrogen exchanger-3 (NHE3) inhibitor that acts locally in the gut to block the NHE3 transporter protein, which is crucial to the paracellular phosphate absorption pathway. Tenapanor has been shown to significantly reduce serum phosphate concentrations compared with placebo, with minimal adverse effects.[185][186][187]​​​​​ Diarrhoea was the most common adverse effect, occurring in 43% to 53% of patients, with approximately 5% of patients developing severe diarrhoea. Most patients had mild or moderate episodes that resolved spontaneously or with a dose reduction.[185][186][187]​ Tenapanor is approved by the FDA as add-on therapy to reduce serum phosphorus levels in CKD patients on dialysis who have had an inadequate response or are intolerant to previously tried phosphate binders. Tenapanor is not approved by the EMA.

Veverimer

Veverimer, a non-absorbed polymer that selectively binds and removes hydrochloric acid from the gastrointestinal lumen, is being investigated for the treatment of metabolic acidosis in patients with CKD. It has been shown to significantly increase serum bicarbonate concentration, with minimal adverse effects. The FDA is currently reviewing an application for approval.[188][189]

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