Yspsl (Rpsgl-Ig) for the Prevention of Delayed Graft Function (Dgf): Results of Double-Blind, Placebo-Controlled, Multi-Center Phase I/Ii Safety and Efficacy Study

Abstract

Oral Abstracts2 9 0 THURSDAY Supplement to Transplantation July 27, 2008, Volume 86 Number 2S was Lebanese. Indications for liver transplantation were as follows: hepatitis C cirrhosis (n=29); hepatitis B cirrhosis (n=13); cryptogenic cirrhosis (n=6); hepatitis B and C co-infection cirrhosis (n=1), primary biliary cirrhosis (n=1) and hepatocellular carcinoma (n=24). All patients were either on the KFSH waiting list for liver transplantation or were denied liver transplantation in KFSH or Egypt due to unsuitable medical condition such as old age or advanced hepatocellular carcinoma (HCC). One year, 3-year and 5-year cumulative patient survival rates were 83%, 62%, and 62% respectively compared to 92%, 84% and 71% in KFSH. Median survival time of the patients was signifi cantly less than that of those transplanted in KFSH (p=0.01). One year, 3-year and 5-year cumulative graft survival rates were 81%, 59%, and 59% respectively compared to 90%, 84% and 71% in KFSH. Of the surviving patients, many suffered from multiple other morbidities. Compared to the patients transplanted in KFSH, the incidence of complications was signifi cantly higher especially biliary complications (p=0.01), sepsis (p=0.003), rejection (p=0.04), metastasis (p=0.03) and acquired HBV infection posttransplant (p=0.02). In addition, requirement of postoperative interventions (radiologic and laparotomy) as well as hospital admissions, were signifi cantly higher hence constituting a higher burden on the resources of the hospital. Conclusion: Our data shows clearly that there is a high mortality and morbidity rate in Saudi and Egyptian patients receiving transplantation in China. This could be related to poor selection criteria, long warm ischemia time, or poor post transplant care. . Although cadaveric liver transplantation in China could be an option for desperate Egyptian and Saudi patients with end stage liver disease, patients and clinicians should be aware of the possible outcomes LATE BREAKING

Surprising up‐regulation of P‐selectin glycoprotein ligand‐1 (PSGL‐1) in endotoxin‐induced uveitis

“…The translational potential of this approach to treat or prevent recurrence of uveitis is further supported by the fact that the soluble PSGL-Ig we used in our study for competitive inhibition is a fully human recombinant fusion protein of PSGL-1 and IgG-1 (41). This protein has been used in clinical trials for acute myocardial infarction (42) and for renal (43) and liver transplant patients for prevention of IR injury (Elizabeth C. Squire, Y's Therapeutics, personal communication, June 20, 2007).…”

Selectin inhibitors: a patent review

“…In a Phase II trial completed in 2008, YSPSL was shown to significantly improve early graft function in terms of serum creatinine reduction and increased glomerular filtration rate, specifically in patients at high risk for renal IRI. YSPSL also reduced expression of IRI biomarkers [60]. An additional Phase II in cadaveric liver transplant is reportedly ongoing [61].…”

YSPSL (rPSGL‐Ig) for improvement of early renal allograft function: a double‐blind, placebo‐controlled, multi‐center Phase IIa study1,2,3

“…In cohort 1 (YSPSL 3.5 mg/kg IV only), the c max was 113 ± 49 mg/mL, the AUC was 28314 ± 9561 h mg/mL, and the serum half‐life was 98 ± 55 h. In cohort 2 (YSPSL 1 mg/kg ± YSPSL flush), the c max was 41.4 ± 7.9 mg/mL, the AUC was 5850 ± 2225 h mg/mL, and the serum half‐life was 114 ± 67 h, and the PK was not different between the patients without and those with YSPSL donor organ flush. These data, combined with part A (23), showed clear linearity between the YSPSL dose and the C max and AUC.…”

“…The safety of YSPSL was previously studied in healthy volunteers, patients with cardiac ischemia (21, 22), and in a phase 1b dose escalation study in kidney transplant recipients (23).…”