Molidustat Promising for Renal Anemia
The investigational drug appeared safe and effective in 3 phase 2b trials.
Molidustat, an investigational medication, effectively treats anemia in patients on hemodialysis (HD) and those with chronic kidney disease (CKD) not on dialysis, according to results from 3 phase 2b trials.
In all 3 DIALOGUE (DaIly orAL treatment increasing endOGenoUs Erythropoietin) trials, which included 100 to 200 participants each, molidustat, a novel, oral hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor, increased or maintained Hb levels over 16 weeks.
In DIALOGUE 1, mean estimated Hb increased by 1.4 to 2.0 g/dL in nondialysis CKD patients treated with molidustat (25 or 50 mg once or twice daily or 75 mg once daily) compared with placebo, Iain C. Macdougall, MBChB, MD, of King's College Hospital, Denmark Hill in London and colleagues reported in the Clinical Journal of the American Society of Nephrology. In DIALOGUE 2, molidustat (starting dose 25 to 75 mg daily) maintained mean Hb within a target range of 10 to 12 g/dL in nondialysis patients switched from darbepoetin. In DIALOGUE 4, molidustat (75 and 150 mg daily) maintained Hb within the target range in HD patients switched from epoetin.
In DIALOGUE 2, Hb increased by a mean 0.6 g/dL more in the molidustat than darbepoetin arm. In DIALOGUE 4, Hb changed -0.1 and 0.4 g/dL in the molidustat vs epoetin arm, depending on dose. According to the investigators, a molidustat starting dose of 25 or 50 mg once daily may be more appropriate than 75 mg once daily in the nondialysis population to prevent Hb from rising above limits. For HD patients, only molidustat starting doses of 75 and 150 mg once daily were effective.
Most adverse events with molidustat were mild or moderate in severity. No serious thromboembolic events were related to treatment.
Studies of other HIF-PH inhibitors, including vadadustat, roxadustat, and daprodustat, have also demonstrated efficacy.
“In conclusion, results of these phase 2b studies indicate that the overall efficacy/safety profile of molidustat enables further development in both patients with CKD who are not on dialysis and those with CKD who are on dialysis,” the authors wrote.
The DIALOGUE trials were funded by Bayer AG.
Dr Macdougall's team acknowledged study limitations that included low patient number in each treatment arm and relatively short duration of treatment contributing to changes in Hb levels observed following start of treatment. They pointed out, however, that these limitations are customary for phase 2 trials, “which serve to provide data from which to design larger, longer phase 3 trials.”
DIALOGUE 1 included 121 patients (101 and 20 in the molidustat and placebo arms, respectively), DIALOGUE 2 included 124 patients (92 and 32 in the molidustat and darbepoetin arms, respectively), and DIALOGUE 4 included 199 patients (157 and 42 in the molidustat and epoetin arms, respectively).
Macdougall IC, Akizawa T, Berns JS, Bernhardt T, and Krueger T. Effects of Molidustat in the treatment of anemia in chronic kidney disease. Clin J Am Soc Nephrol. DOI:10.2215/CJN.02510218