Tadao Akizawa1, Iain C Macdougall2, Jeffrey S Berns3, Thomas Bernhardt4, Gerald Staedtler4, Megumi Taguchi5, Kazuma Iekushi5, Thilo Krueger6. 1. Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan, akizawa@med.showa-u.ac.jp. 2. Department of Renal Medicine, King's College Hospital, London, United Kingdom. 3. Perelman School of Medicine at the University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. 4. Research & Development, Pharmaceuticals, Bayer AG, Berlin, Germany. 5. Medical Affairs, Pulmonology & Cardiology, Bayer Yakuhin Ltd., Osaka, Japan. 6. Research & Development, Pharmaceuticals, Bayer AG, Wuppertal, Germany.
Abstract
BACKGROUND: Molidustat, a novel hypoxia-inducible factor-prolyl hydroxylase inhibitor, is being investigated for the treatment of anemia associated with chronic kidney disease (CKD). The efficacy and safety of molidustat were recently evaluated in three 16-week phase 2b studies. Here, we report the results of two long-term extension studies of molidustat. METHODS: Both studies were parallel-group, open-label, multicenter studies of ≤36 months' duration, in patients with anemia due to CKD, and included an erythropoiesis-stimulating agent as active control. One study enrolled patients not receiving dialysis (n = 164), and the other enrolled patients receiving hemodialysis (n = 88). The primary efficacy variable for both studies was change in blood hemoglobin (Hb) level from baseline to each post-baseline visit, and safety outcomes included adverse events (AEs). RESULTS: In patients not on dialysis, the mean ± SD Hb concentrations at baseline were 11.28 ± 0.55 g/dL for molidustat and 11.08 ± 0.51 g/dL for darbepoetin. The mean ± SD blood Hb concentrations throughout the study (defined as mean of each patient's overall study Hb levels) were 11.10 ± 0.508 and 10.98 ± 0.571 g/dL in patients treated with molidustat and darbepoetin, respectively. Similar proportions of patients reported at least one AE in the molidustat (85.6%) and darbepoetin (85.7%) groups. In patients on dialysis, mean ± SD Hb levels at baseline were 10.40 ± 0.70 and 10.52 ± 0.53 g/dL in the molidustat and epoetin groups, respectively. The mean ± SD blood Hb concentrations during the study were 10.37 ± 0.56 g/dL in the molidustat group and 10.52 ± 0.47 g/dL in the epoetin group. Proportions of patients who reported at least one AE were 91.2% in the molidustat group and 93.3% in the epoetin group. CONCLUSIONS: Molidustat was well tolerated for up to 36 months and appears to be an effective alternative to darbepoetin and epoetin in the long-term management of anemia associated with CKD.
BACKGROUND:Molidustat, a novel hypoxia-inducible factor-prolyl hydroxylase inhibitor, is being investigated for the treatment of anemia associated with chronic kidney disease (CKD). The efficacy and safety of molidustat were recently evaluated in three 16-week phase 2b studies. Here, we report the results of two long-term extension studies of molidustat. METHODS: Both studies were parallel-group, open-label, multicenter studies of ≤36 months' duration, in patients with anemia due to CKD, and included an erythropoiesis-stimulating agent as active control. One study enrolled patients not receiving dialysis (n = 164), and the other enrolled patients receiving hemodialysis (n = 88). The primary efficacy variable for both studies was change in blood hemoglobin (Hb) level from baseline to each post-baseline visit, and safety outcomes included adverse events (AEs). RESULTS: In patients not on dialysis, the mean ± SD Hb concentrations at baseline were 11.28 ± 0.55 g/dL for molidustat and 11.08 ± 0.51 g/dL for darbepoetin. The mean ± SD blood Hb concentrations throughout the study (defined as mean of each patient's overall study Hb levels) were 11.10 ± 0.508 and 10.98 ± 0.571 g/dL in patients treated with molidustat and darbepoetin, respectively. Similar proportions of patients reported at least one AE in the molidustat (85.6%) and darbepoetin (85.7%) groups. In patients on dialysis, mean ± SD Hb levels at baseline were 10.40 ± 0.70 and 10.52 ± 0.53 g/dL in the molidustat and epoetin groups, respectively. The mean ± SD blood Hb concentrations during the study were 10.37 ± 0.56 g/dL in the molidustat group and 10.52 ± 0.47 g/dL in the epoetin group. Proportions of patients who reported at least one AE were 91.2% in the molidustat group and 93.3% in the epoetin group. CONCLUSIONS:Molidustat was well tolerated for up to 36 months and appears to be an effective alternative to darbepoetin and epoetin in the long-term management of anemia associated with CKD.
Authors: Matthew R Weir; Pablo E Pergola; Rajiv Agarwal; Jeffrey C Fink; Nelson P Kopyt; Ajay K Singh; Jayant Kumar; Susanne Schmitt; Gregor Schaffar; Anita Rudy; Jim P McKay; Radmila Kanceva Journal: Am J Nephrol Date: 2017-10-30 Impact factor: 3.754
Authors: Meenakshi Patel; David G Thimons; Jaron L Winston; Wayne Langholff; Tracy McGowan Journal: J Am Med Dir Assoc Date: 2010-11-11 Impact factor: 4.669
Authors: Scott D Solomon; Hajime Uno; Eldrin F Lewis; Kai-Uwe Eckardt; Julie Lin; Emmanuel A Burdmann; Dick de Zeeuw; Peter Ivanovich; Andrew S Levey; Patrick Parfrey; Giuseppe Remuzzi; Ajay K Singh; Robert Toto; Fannie Huang; Jerome Rossert; John J V McMurray; Marc A Pfeffer Journal: N Engl J Med Date: 2010-09-16 Impact factor: 91.245
Authors: Bruce F Culleton; Braden J Manns; Jianguo Zhang; Marcello Tonelli; Scott Klarenbach; Brenda R Hemmelgarn Journal: Blood Date: 2006-01-10 Impact factor: 22.113
Authors: Lynda A Szczech; Huiman X Barnhart; Jula K Inrig; Donal N Reddan; Shelly Sapp; Robert M Califf; Uptal D Patel; Ajay K Singh Journal: Kidney Int Date: 2008-07-02 Impact factor: 10.612
Authors: José Portolés; Jose Luis Gorriz; Esther Rubio; Fernando de Alvaro; Florencio García; Vicente Alvarez-Chivas; Pedro Aranda; Alberto Martinez-Castelao Journal: BMC Nephrol Date: 2013-01-07 Impact factor: 2.388