Improvements in Calcific Uremic Arteriolopathy Wound Healing During SNF472 Treatment, Results of a Phase 2 Trial

Background: Calcific uremic arteriolopathy (CUA/calciphylaxis) in patients with end-stage renal disease is a severe form of vascular calcification characterized by painful necrotic skin ulcers and very high mortality. No approved therapies are available. SNF472, an investigational drug, is an intravenous formulation of myo-inositol hexaphosphate that inhibits formation and growth of hydroxyapatite crystals, the final common step in vascular calcification pathophysiology. 

Methods: In this open-label single-arm trial, 14 patients with CUA were treated with SNF472 3x/week during each hemodialysis session for up to 12 weeks, added to standard of care. The primary endpoint was change from baseline to Week 12 in wound healing, assessed using the Bates-Jensen Wound Assessment Tool (BWAT). Secondary endpoints included pain on a visual analog scale (VAS), qualitative review of wound images, and a wound-associated quality-of-life questionnaire (Wound-QoL). For a post-hoc analysis, a targeted modification of BWAT, the “BWAT-CUA”, was derived by an interdisciplinary group of experts. BWAT-CUA focuses on prototypical CUA features: necrotic tissue type, necrotic tissue amount, exudate type, exudate amount, skin color surrounding wound, peripheral tissue edema, peripheral tissue induration, and granulation tissue.  

Results: Eleven patients completed the 12-week treatment. There were significant improvements from baseline to Week 12 in total BWAT, qualitative wound image review, Pain VAS, and Wound-QoL. In addition, mean(SE) BWAT-CUA improved from 21.2 (2.0) at baseline to 14.9 (1.4) at Week 12 (p<0.002). Among the BWAT items, the largest improvements were observed for peripheral tissue induration, skin color surrounding wound, and granulation tissue. Adverse events were consistent with the patient population and no serious adverse event was assessed as related to SNF472.

Conclusion: These results suggest SNF472 may have benefits across multiple parameters. A Phase 3, placebo-controlled trial of SNF472 for CUA is under development. BWAT-CUA, an objective and quantitative tool targeted for the evaluation of CUA wound healing, will be a primary endpoint.