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Improvement in wound healing, pain, and quality of life after 12 weeks of SNF472 treatment: a phase 2 open-label study of patients with calciphylaxis

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Abstract

Background

Calciphylaxis in end-stage renal disease is characterized by painful necrotic skin ulcers and high mortality. There are no approved therapies. SNF472, an intravenous formulation of myo-inositol hexaphosphate, inhibits the formation and growth of hydroxyapatite crystals, the final common pathway in the pathogenesis of vascular calcification.

Methods

In this open-label, single-arm study, calciphylaxis patients on thrice-weekly hemodialysis and standard care, received intravenous SNF472 3 times per week for 12 weeks. The primary endpoint was wound healing assessed using the quantitative Bates-Jensen Wound Assessment Tool (BWAT). Pain visual analog scale (VAS), quality of life (wound-QoL), and qualitative wound image review were secondary endpoints. Quantitative changes from baseline were analyzed by paired t-tests using multiple imputation to account for missing observations.

Results

Fourteen patients received SNF472. Improvements from baseline to week 12 were observed for mean BWAT score (− 8.1; P < 0.001), pain VAS (− 23.6 mm; P = 0.015) and wound-QoL global score (− 0.90; P = 0.003). Of the 9 patients with ulcerated lesions at baseline who completed treatment, wound image review showed improvement for 7. SNF472 was well tolerated with no serious treatment-related adverse events. The most common adverse events were infections which occur frequently in patients on hemodialysis. None of these were considered as treatment-related.

Conclusions

SNF472 was well-tolerated and improvements from baseline to week 12 in wound healing, pain, and quality of life were observed. A randomized, double-blind, placebo-controlled trial is planned to evaluate SNF472 in patients with calciphylaxis.

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Acknowledgements

The study was supported by Laboratoris Sanifit. Medical writing support from Jonathan Latham of PharmaScribe, LLC was funded by Sanifit. The study was conducted in the US at Frenova Renal Research® and Davita Kidney Care sites, and in the UK at the Salford Royal NHS Foundation Trust. Sanifit thanks Dr. Barbara Bates-Jensen for permission to use the BWAT in this study.

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Authors and Affiliations

  1. Department of Cardiology, Nephrology, and Intensive Care Medicine, Rhein-Maas Klinikum, Mauerfeldchen 25, 52146, Würselen, Germany

    Vincent M. Brandenburg

  2. Salford Royal NHS Foundation Trust, Salford, UK

    Smeeta Sinha

  3. University of Manchester, Manchester, UK

    Smeeta Sinha

  4. Nephrology Department, Hospital Clinic, Barcelona, Spain

    Jose-Vicente Torregrosa

  5. Sanifit Therapeutics, San Diego, CA, USA

    Rekha Garg, Stephan Miller, Daun Bahr & Alex Gold

  6. Sanifit Therapeutics, Palma, Spain

    Ana-Zeralda Canals, Carolina Salcedo & Joan Perelló

  7. King’s College, London, UK

    Pieter H. Joubert

  8. KJC Statistics, Cheshire, UK

    Kevin J. Carroll

  9. University of the Balearic Islands, Palma, Spain

    Joan Perelló

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Contributions

VB, SS, JT, AZC, PJ, CS, and JP contributed to the study concept and design. VB and SS contributed to the acquisition of data. VB, SS, RG, SM, AZC, CS, KJC, AG, and JP contributed to the conduct, analysis and interpretation of the data. SM and RG drafted the article. All authors contributed to critical editing and revising the article for important intellectual content. All authors provided final approval of the version to be published. All authors agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Vincent M. Brandenburg.

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Conflict of interest

VB is a consultant to Pharmacosmos, Vifor, and FMC, received lecture fees from Amgen, Pfizer, Bayer, Pharmacosmos, Vifor, FMC, Servier, Novartis, Daiichi-Sankyo, and Cardiobridge, received a grant for the European Calciphylaxis Network EuCalNet from Amgen, and received grants from Pfizer, Bayer, Sanifit, Pharmacosmos, Vifor, FMC, Servier, Novartis, Daiichi-Sankyo, and Cardiobridge. SS is a consultant to Sanifit, and received lecture fees from Vifor Fresenius, MSD, and Boehringer Ingelheim. JT has no conflicts to disclose. KJC and PJ, are consultants to Sanifit. RG, SM and AG are employees and shareholders of Sanifit Therapeutics. AZC is an employee and shareholders of Sanifit and has a patent pending related to SNF472. CS is an employee of Sanifit and has patents related to SNF472. JP is an employee and shareholder of Sanifit, and has patents owned or controlled by Sanifit.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Brandenburg, V.M., Sinha, S., Torregrosa, JV. et al. Improvement in wound healing, pain, and quality of life after 12 weeks of SNF472 treatment: a phase 2 open-label study of patients with calciphylaxis. J Nephrol 32, 811–821 (2019). https://doi.org/10.1007/s40620-019-00631-0

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