Vascarta, a clinical-stage biopharmaceutical company advancing innovative treatments for pain and inflammation, has announced successful completion of the sublingual arm of its phase 1 clinical trial evaluating VAS-101 (Vasceptor, topical curcumin gel) for the treatment of sickle cell disease (SCD).
The study was conducted by the Foundation for Sickle Cell Disease Research (FSCDR) in Hollywood, Florida, under the supervision of the principal investigator, Dr Gershwin Blyden. The findings were published today in the Journal of Sickle Cell Disease.
Five patients with sickle cell disease were treated sublingually with a minimal dosing (0.1 mL) of VAS-101 twice per week for a total of eight treatments. Their blood was drawn and analysed weekly. The duration of treatment was 29 days. All participants demonstrated favourable safety and tolerability. Directional improvements were observed across several patient-reported outcomes. Mean pain scores decreased from 7.0 at baseline to 6.6 by day 15, with several participants demonstrating clinically meaningful reductions from baseline. Measures of fatigue and energy also improved, with out-of-energy scores decreasing from 3.6 at baseline to 2.2 by day 22 and fatigue limits improving from 2.8 to 2.0.
Psychosocial ePRO measures showed stability or improvement across most participants, including reductions in worry, loneliness and depressive symptoms. Assessment of red blood cell (RBC) functional biomarkers demonstrated improvements as measured by the DSA. From baseline to day 29, the Area Under the Curve (AUC10) decreased from 419±140 to 394±118 %*min. Morphological point of sickling at 50% (mPoS@50%) increased from 4.9±1.0 to 5.5±1.2 minutes, indicating a delay in sickling. Additionally, the rate of sickling decreased from 47±23 to 38±17 %/min.
Collectively, these changes reflect improved sickling kinetics over the treatment period. FA-WB-VCAM and FA-WB-Psel adhesion indices (fAI) were below previously established critical thresholds (FA-WB-VCAM:400 cells/mm2, FA-WB-Psel:50 cells/mm2) predictive of future self-reported vaso-occlusive crises, VOCs in four subjects at baseline and, as expected, no improvements in adhesion were seen at Day 29. Only a single participant exhibited a baseline FA-WB-VCAM fAI exceeding the clinical threshold (>502 cells/mm²).
Red blood cell mechanical fragility indices (MFI) were within normal range at baseline and remained stable over the course of the study. Baseline concentrations of standard inflammatory markers were and remained below the lower limit of detection for the initial three participants; consequently, further analytical testing was suspended.
VAS-101 demonstrated safety and tolerability in the sublingual cohort. Improvements in integrated ePRO and RBC functional biomarkers were noted suggesting potential mechanistic and patient-centred benefits of VAS-101 in individuals with SCD. The resulting biomarkers shift at low dose supports advancement towards dose optimisation. Future studies evaluating higher dose and frequency may yield greater improvements in pain, ePRO measures, and laboratory biomarkers. Pre-selecting a cohort that exhibits a higher adhesive burden, indicative of more inflammation may show further improvements in RBC health normalisation.
