Pharming Reports Positive Data From First Investigator-initiated Study of rhC1-Inhibitor (RUCONEST) in Contrast-induced Nephropathy
LEIDEN, Netherlands, October 17, 2018 /PRNewswire/ --
Primary Endpoint was met, with rhC1INH treatment reducing neutrophil gelatinase-associated lipocalin (NGAL), a widely recognized marker of acute renal damage
Pharming Group N.V. ("Pharming" or "the Company") (Euronext Amsterdam: PHARM) today 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.
Dr Michael Osthoff, Basel University Hospital Basel, Basel, Switzerland and Primary Investigator, said:
"We are very pleased that we were able to provide an early proof-of-concept that dosing RUCONEST ahead and following contrast enhanced investigations and interventions, particularly in those patients that have to undergo PCI, may limit subsequent damage to these patients' kidneys. We believe that these positive results merit further clinical investigations and confirmation in a larger trial, and we are very keen to continue the collaboration with Pharming."
Dr Bruno Giannetti, Chief Operations Officer of Pharming, said:
"Reaching a significant difference already in a small number of patients in this well-run exploratory trial gives a surprisingly clear positive signal in what could become a large new indication for RUCONEST.
"Furthermore, invasive interventions requiring contrast medium applications, like PCI, are known to cause damage to organs like the kidney and the brain through small thromboembolic events triggering complement cascade activation. RUCONEST is a recombinant form of the most important element of the body's own complement activation braking system. NGAL is a sensitive indicator to detect and assess this combined damage in this particular situation. These results therefore also provide important predictive information on the potential protective effects of RUCONEST in a number of other indications like pre-eclampsia or reperfusion injuries, in which complement activation is thought to play an important role."
As planned, Pharming has filed for regulatory approval in the Netherlands and shortly also in Australia to begin the first clinical study of RUCONEST in pre-eclampsia.
About Contrast-induced Acute Kidney Injury ("CI-AKI")
Acute kidney injury (AKI) affects 13-18% of all patients admitted to hospital in developed countries. The estimated general incidence of CI-AKI is approximately 7%. Its incidence may increase to >50% in the presence of risk factors such as chronic kidney disease, diabetes mellitus and nephrotoxic drugs.