Pharming reports positive data from first investigator-initiated study of rhC1-Inhibitor (RUCONEST®) in Contrast-induced NephropathyWednesday, October 17, 2018
Pharming Group N.V. announced positive results from a Phase II investigator-initiated study of RUCONEST® (recombinant human C1 esterase inhibitor, or “rhC1INH”) in a double-blind, placebo-controlled clinical trial in patients at risk of nephropathy resulting from contrast-enhanced examinations.
The study was led by Dr. Michael Osthoff at the University Hospital Basel, Basel, Switzerland. 75 eligible patients with known moderate to severe renal function impairment were given either 50 units per kg (up to 4200 units) of RUCONEST® (n=37) or placebo (n=38) immediately prior to treatment with standard-of care contrast medium as part of an elective coronary angiography with or without a percutaneous coronary intervention (“PCI”), and then a second identical treatment four hours after the intervention.
In the overall study, RUCONEST® showed a statistically-significant effect (p= 0.038) in reducing the rise in urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), the primary endpoint for the study and a generally recognized early marker of acute renal injury, in patients with diagnosed renal function impairment undergoing interventions enhanced with standard contrast media such as PCIs.
The results were especially clear in the sub-group of patients (n=30) undergoing PCI. The intent-to-treat analysis in this group showed that patients on RUCONEST® had a median increase in peak urinary NGAL concentration within 48 hours of 1.8 ng/ml compared with an increase of 26.2 ng/ml in the placebo arm (p=0.04). This corresponds to a clear difference in the median percentage change in the peak urinary NGAL level within 48 hours of 11.3% in the RUCONEST® arm and 205.2% in the placebo arm (p=0.001).
The overall assessment of the study also showed trends that patients undergoing more invasive interventions and procedures requiring higher volumes of contrast medium experienced a stronger benefit from the RUCONEST® treatment.
The treatment also showed an excellent safety profile comparable to the placebo group – a particularly significant observation considering the high-risk patient group included in the study (average age approximately 77 years, with multiple comorbidities and impaired kidney function)
This data therefore supports additional clinical investigations for the use of rhC1INH in a new indication where there is significant unmet medical need.
A secondary endpoint measured was Troponin T, a marker of cardiovascular damage caused by the examination or intervention itself, but this did not show a meaningful difference in the overall study population: the power of the study and the variety of interventions applied were not suitable to perform an appropriate evaluation.
Following these positive results, Pharming will continue discussions with Dr. Osthoff and other experts in this area with the aim to perform further clinical development to establish the efficacy and efficiency of RUCONEST® treatment in the patient group likely to experience the greatest benefit. Dr. Osthoff will be publishing the full results of his study in due course.