Our CFTR program with GLPG2737 in ADPKD
Autosomal dominant polycystic kidney disease (ADPKD) affects approximately 12.5 million people worldwide and is the fourth leading cause of kidney failure today.1 Typically with this disease, both kidneys enlarge with fluid-filled cysts, leading to kidney failure for approximately half of patients by the age of 60, and requiring dialysis and possibly kidney transplantation.2 Patients may also suffer from hypertension, abdominal pain, kidney infections, cyst ruptures, bleeding, and other symptoms impacting quality of life. Other organs may be affected as well. Treatment is aimed at relieving symptoms and controlling the accompanying hypertension. Currently, only one therapy (tolvaptan3) is available to slow down the progression of cyst development and renal insufficiency; however, not all patients tolerate this therapy.4
GLPG2737 is a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) inhibitor which was observed to be well tolerated by patients in previous clinical trials. It is hypothesized that inhibition of the CFTR channel might reduce cyst growth and kidney enlargement for patients with ADPKD.
We are currently investigating GLPG2737 in the MANGROVE Phase 2 randomized, double-blind, placebo-controlled trial evaluating a once-daily oral dose of GLPG2737. GLPG2737 or placebo is administered for 52 weeks, followed by an open-label extension period of 52 weeks, in 66 ADPKD patients with rapidly progressing disease. The primary objectives of the trial are to assess the effect on growth of total kidney volume over 52 weeks compared to placebo as well as overall safety and tolerability. The secondary objectives include renal function, pharmacokinetics, and pharmacodynamics.
In November 2021 we announced completion of patient recruitment in the MANGROVE study, with topline results anticipated in the first half of 2023.
1 1Chebib F.T., Torres V.E. Autosomal Dominant Polycystic Kidney Disease: Core Curriculum 2016. Am J Kidney Dis. May 2016, 67 (5) 792-810
2 2Parfrey P.S., Bear J.C., Morgan J., Cramer B.C., McManamon P.J., Gault M.H., et al. The diagnosis and prognosis of autosomal dominant polycystic kidney disease. N Engl J Med. 1990;323(16):1085–90
3 3Jynarque®, Otsuka
4 4Chebib F.T., Perrone R.D., Chapman A.B., Dahl N.K., Harris P.C., Mrug M., et al. A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan. JASN. October 2018, 29 (10) 2458-2470