Regulatory Decision Summary for Velphoro
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
Type of submission:
What was the purpose of this submission?
A New Drug Submission (NDS) for Velphoro (Sucroferric oxyhydroxide) was filed to seek approval for the control of serum phosphorous levels in adult patients with end-stage renal disease (ESRD) undergoing dialysis.
Why was the decision issued?
Hyperphosphatemia has been linked to increased mortality and cardiovascular disease in chronic kidney disease (CKD) patients. Studies have shown that phosphate binder administration decreases all-cause and cardiovascular mortality risks. Velphoro (sucroferric oxyhydroxide) has been developed as an iron-based phosphate binder to manage hyperphosphatemia.
Velphoro has demonstrated significant reductions in serum phosphorus levels in patients with end-stage renal disease on dialysis. The efficacy of Velphoro was compared with that of sevelamer carbonate (a common and standard treatment for patients with hyperphosphatemia) in an open-label, randomized, active-controlled phase III study. Velphoro was able to control hyperphosphatemia, according to the CKD guidelines, up to one year in half of the treated population with a comparable safety profile to sevelamer. The maintenance dose of Velphoro has demonstrated superiority over the Velphoro non-effective low dose in controlling serum phosphorus levels. The long-term maintenance of serum phosphorus levels with Velphoro treatment for up to 12 months has also been demonstrated. The efficacy of Velphoro is consistent across all sub-groups (sex, age, ethnicity and geographic region). Clinically relevant efficacy was shown in patients on hemodialysis (HD) and peritoneal dialysis (PD), although the latter formed a minority of the total studied patient population.
Throughout all the studies in the clinical development programme, Velphoro was well tolerated at the proposed doses. The safety profile of Velphoro, as with other non-absorbed medicines, is primarily defined by gastrointestinal (GI) adverse events (AEs) including diarrhea. The majority of these diarrhea AEs occurred early after starting treatment, were mild in severity, and resolved with continued use of Velphoro. Although no marked differences in the severity of AEs were noted in the pivotal studies when compared to sevelamer, a higher proportion of patients discontinued for gastrointestinal AEs in the Velphoro group compared to sevelamer. Discontinuation rates were markedly lower for patients in the long-term extension study on Velphoro.
No new or significant safety signals emerged with long-term treatment in the analysis of the safety extension study. Based upon a review of the post-marketing data, the safety profile of Velphoro remains unchanged and no issues have arisen that would recommend changes to prescribing information.
Velphoro is an iron-based phosphate binder and the nonclinical studies have shown minimal release of iron from Velphoro in the GI tract. In the clinical studies, Velphoro showed increases in iron parameters (ferritin and transferrin saturation) early during treatment and then stabilising, indicating that minimal iron absorption cannot be excluded. Long-term data did not show an increased risk of iron accumulation or adverse events related to iron parameters. In current clinical practice, CKD patients on dialysis are commonly administered significant amounts of IV iron averaging 5 to 7 mg per day. These patients also have their iron status, including hemoglobin, regularly assessed and as such, any increase in iron stores will be detected early, and their IV iron treatment adjusted accordingly. Therefore, the risk of iron overload with long-term treatment with Velphoro is minimal. The risk of iron accumulation was reflected in the Warnings and Precautions section of the Product Monograph.
The recommended starting dose of Velphoro is 1,500 mg iron (3 tablets) per day, divided across the meals of the day. In common with clinical practice, Velphoro will be titrated for each patient to account for individual differences in factors such as dietary habits and medical conditions.
In conclusion, the clinical studies have demonstrated that Velphoro has a favourable benefit/risk profile which offers a new option for the treatment of hyperphosphatemia in patients with end-stage renal disease on dialysis.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.