Abstract: SA-PO687
Pharmacokinetics and Pharmacodynamics of SNF472 in Calciphylaxis Patients: Results from a Phase 2 Clinical Trial (SNFCT2015_04)
Session Information
- Bone and Mineral Metabolism: Clinical - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Salcedo, Carolina, Laboratoris Sanifit, Palma de Mallorca, Illes Balears, Spain
- Ferrer, Miquel D., Laboratoris Sanifit, Palma de Mallorca, Illes Balears, Spain
- Perez, Maria del mar, Laboratoris Sanifit, Palma de Mallorca, Illes Balears, Spain
- Canals, Ana-Zeralda, Laboratoris Sanifit, Palma de Mallorca, Illes Balears, Spain
- Perelló, Joan, Laboratoris Sanifit, Palma de Mallorca, Illes Balears, Spain
Background
SNF472 is a selective calcification inhibitor that interferes in the formation and growth of hydroxyapatite crystals. It is being developed for the treatment of calciphylaxis (CUA), a severe form of vascular calcification that affects the small vessels under the skin in patients with end-stage renal disease on hemodialysis (HD).
Methods
This was an open label, single arm trial investigating the effect of SNF472 on top of standard of care in the treatment of CUA in HD patients. Patients were treated for 12 weeks with intravenous 6-9 mg/kg of SNF472 three times per week during each dialysis session. The dose (400, 450, 700 or 900 mg) was adjusted by body weight categories. SNF472 levels were measured in plasma samples obtained pre-HD (baseline) and at the end of SNF472 infusion on the first and the last treatment sessions. Another aliquot of plasma was used to measure ex-vivo the propensity of plasma to induce calcium phosphate (CaP) crystallization as a pharmacodynamic (PD) measurement.
Results
The study enrolled 14 patients with 11 completing the treatment. The maximum SNF472 concentration in plasma was 29.1 ± 19.1 µM in week 1 and 26.3 ± 21.3 µM in week 12. There was no accumulation of SNF472 or any effect of repeated administration for up to 12 weeks in the exposure to the compound, confirming the results of a previous phase 1b trial in HD patients. The ex-vivo induction of CaP crystallization was inhibited up to 65 ± 14% after treatment with SNF472 (week 1) and up to 60 ± 29% at week 12. No differences attributable to the doses tested were observed concerning the PD effect, as all doses were on the plateau of the effect. These results were in accordance with the previous data seen in the Phase 1b trial. No inhibition of crystallization was evidenced in one patient that did not present detectable SNF472 levels (<0.76 µM) after treatment at week 12, showing a relationship between SNF472 circulating levels and PD.
Conclusion
These results suggest that the administration of SNF472 to CUA patients on HD allows to attain potentially therapeutic levels, as evidenced by both its circulating levels and the inhibition of ex-vivo calcification induction.
Funding
- Commercial Support – Laboratoris Sanifit