MedPage Today (6/25, Gever) reported that, according to studies published in the New England Journal of Medicine, “the mTOR inhibitors everolimus (Zortress, Afinitor) and sirolimus (Rapamune) failed to halt the decline in renal function associated with autosomal dominant polycystic kidney disease (ADPKD). “In one study of 433 patients, researchers found that “renal volume growth was slowed with everolimus, but the treatment had no effect on the glomerular filtration rate (eGFR).” Meanwhile, 100 “patients in the second trial, who had less advanced disease, fared no better sirolimus: neither renal volume nor GFR were affected any differently by the drug relative to placebo.” An editorial accompanying the studies “summed up the disappointment of the nephrology community.” e-Published ASN Online Kidney Daily, June 28, 2010.
Jill Panetta, PhD, Chief Scientific Officer, PKD Foundation said, “While the results are somewhat disappointing from these two studies, there are other trials on-going. In addition, we’re now developing a comprehensive plan for speeding up the drug-development process and building a clinical trials pipeline. This we hope to soon share with the PKD community.”
For some time it has been known that sirolimus and everolimus cause side effects no one would welcome when used at doses commensurate to those used in laboratory animals that showed efficacy. Nonetheless, these are interesting compounds and are representatives of a class of drugs that may have benefit in a modified format.
For more information about these studies, please see below:
Everolimus in Patients with Autosomal Dominant Polycystic Kidney Disease
Sirolimus and Kidney Growth in Autosomal Dominant Polycystic Kidney Disease
mTOR inhibitors in Polycystic Kidney Disease