6-year treatment follow-up with an extended-release alkaline formulation (Sibnayal) in primary distal renal tubular acidosis.

BACKGROUND

Distal renal tubular acidosis (dRTA) is a rare disease characterized by hyperchloremic metabolic acidosis affecting growth, bone and kidney health.

METHODS

The aim of B22CS study was to evaluate long-term safety and efficacy (anthropometric/pubertal, tubular damages/kidney function, bone biomarkers, compliance assessments) of Sibnayal, a prolonged-release alkalinizing formulation with twice daily dosing, in children and adults with dRTA. All patients were previously included in the pivotal B21CS study, so were already receiving Sibnayal when included in B22CS open-label follow-up study.

RESULTS

A total of 30 patients with primary dRTA (mean age:10.6 ± 6.0 years) entered this long-term study (average of 6 years). At inclusion, most patients had adequate metabolic control, normal kidney function and height. Sibnayal was well tolerated over the study duration.The most frequent adverse event was hypovitaminosis D (13 patients). Causality to treatment was reported for only 4% of all TEAEs (6 patients) and were mostly gastrointestinal. All adverse events resolved without treatment discontinuation. Sibnayal allowed a sustained control of metabolic acidosis as plasma bicarbonate level was 22.0 ± 3.2 mmol/L at baseline versus 22.6 ± 2.5 mmol/L at the End of Follow-up (EoF), p = NS. From baseline to EoF, mean Z-score height significantly increased (-0.6 ± 1.0 to -0.3 ± 1.0, p = 0.03), without significant change in weight and body mass index. Kidney function remained stable from baseline to EoF: estimated glomerular filtration rate = 105 ± 17 and 104 ± 20 mL/min/1.73m, respectively, p = NS. Urinary ratios: Calcium/Creatinine (UCa/UCr), Citrate/Creatinine (UCi/UCr), Calcium/Citrate (UCa/UCi) were not significantly different between baseline and EoF (p = NS). Mean lumbar bone mineral density Z-score significantly increased from baseline (-1.1 ± 1.0) to EoF (-0.8 ± 1.0), p = 0.005, with significant improvement between baseline and EoF in pre- and post-pubertal patients (p = 0.035 and p < 0.001, respectively), whilst it was maintained in pubertal patients (p = NS).

CONCLUSION

Long-term data support the good safety and efficacy profile of Sibnayal in the treatment of dRTA with adequate control of metabolic acidosis, stable kidney function and significant positive long-term clinical outcomes.