On 1 February, the Clinical Kidney Journal published results from a real-world setting study, the VELREAL multicenter study, which showed a 20% decrease in serum phosphorus in addition to reduced parathyroid hormone level using Vifor Pharma’s Velphoro (sucroferric oxyhydroxide) in chronic kidney disease (CKD) patients on dialysis.
Velphoro was shown to be effective in lowering the number of phosphate binder tablets being taken by patients, and according to simplified medication adherence questionnaire, patient adherence increased by 24.5%. Treatment for hyperphosphatemia (HP) in late-stage CKD involves the use of a phosphate binder therapy such as calcium-based binders, non-calcium metal-based binders, and non-calcium non-metal-based binders.
GlobalData believes that this study could be of high clinical value to physicians with dialysis patients looking to find an optimal treatment of choice for HP. However, key opinion leaders interviewed by GlobalData have emphasised that although the Velphoro pill burden is very low and clinical studies show that it is safe and effective, it has had a slow adoption in the CKD market due to issues with its cost. Despite the needs for developing optimal therapies with advanced safety, efficacy, and compliance profiles, costly branded therapies remain a notable barrier in the CKD-HP treatment space.
Velphoro has previously shown an effective and safe clinical profile. It was found to be non-inferior to Sanofi / Genzyme’s Renvela (sevelamer carbonate) in dialysis patients. Also, the drug was not found to cause a significant amount of iron absorption, and has a lower pill burden compared to sevelamer in a Phase III study for the treatment of HP in dialysis-dependent CKD patients (Vifor Inc., NCT01324128).
However, patient adherence remains a major problem in the HP space since patients have to take a considerable amount of tablets, which makes the market penetration of new therapies difficult unless they show significant benefits in terms of efficacy and safety compared to incumbent therapies such as sevelamer carbonate and lanthanum carbonate. This recent clinical trial demonstrating further efficacy of Velphoro for hemodialysis patients within the real clinical practice setting may bolster the current use of the drug among dialysis patients.
Velphoro is a phosphate binder, which has most recently been incorporated into clinical practice for treatment of HP patients on dialysis. The drug comprises a polynuclear iron (III)-oxyhydroxide core that is stabilised with a carbohydrate shell, which preserves the phosphate adsorption capacity. Dietary phosphate can then bind to Velphoro in the gastrointestinal tract to reduce the absorption of phosphate into the plasma.
The development of iron-based phosphate binders has gained traction in the last years, as they have demonstrated phosphate-binding efficacy and satisfactory safety profiles in several clinical studies. Shield Therapeutics’ PT20 and Ardelyx’s tenapanor are currently in development to help address pill burden for patients with CKD-related HP. Currently in Phase II development, PT20’s adipate-doped iron oxide technology provides a larger surface area and allows for higher-capacity phosphate binding. Therefore, it is expected to require a lower dose and pill burden for patients.
Additionally, Ardelyx believes that tenapanor monotherapy would help improve patient compliance by reducing pill burden, and combination therapy would provide a dual mechanism approach in treating refractory CKD-HP patients, if approved. Ardelyx submitted a New Drug Application to the FDA for tenapanor in June 2020 for the treatment of HP in CKD patients on dialysis. Tenapanor is an inhibitor of the sodium / hydrogen exchanger isoform 3 (NHE3) found in the kidneys, which acts to regulate sodium absorption and secretion in the body under normal physiological conditions.