Molidustat Sodium

Erythropoietic effects of molidustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, occur in anemic cats with chronic kidney disease (CKD).

To evaluate the effectiveness and safety of molidustat in managing anemia in cats with CKD.

Seventy-five client-owned anemic cats with CKD in the effectiveness and safety phase and 64 in the safety continuation phase.

Multicenter, randomized, double-masked, placebo-controlled field study. Cats in the 28-day effectiveness and safety phase received 5 mg/kg of molidustat (n = 40) or a control product (CP; n = 35), once daily for 28 days. During the 20-week safety continuation phase, all cats received 5 mg/kg molidustat in 28-day treatment cycles once PCV declined to < 28%. Individual cat treatment success, defined as a ≥ 4% point increase in hematocrit (HCT) compared to baseline, was evaluated on day 28. Safety was assessed throughout both phases.

Proportion of molidustat-treated cats with treatment success on day 28 (68% ± 7.4%; 95% CI, 51.45-80.28) was significantly higher compared to CP cats (17% ± 6.4%; 95% CI, 7.80-33.59; P < .001). During the safety continuation phase, median treatment cycle duration was 28 days with treatment intermission medians ranging from 11 to 18 days. There was no evidence of adverse effects attributed to molidustat when administered alone or in combination with other medications.

Molidustat significantly increased HCT values in treated cats compared to CP cats. Repeated 28-day treatment cycles were well-tolerated. Molidustat is an effective and safe treatment for long-term management of anemia in cats with CKD.

Airborne RNA viruses of the Paramyxoviridae family are major human pathogens. These include measles virus (MeV) and Nipah virus (NiV), the latter being on the World Health Organization's blueprint list due to its high case-fatality rate and critical risk of emergence. Although an effective vaccine is available for MeV, this is not the case for NiV. Moreover, there is no cure for MeV- or NiV-infected patients that prevents the acute respiratory syndrome or lethal encephalitis. To identify new host factors to target for inhibiting viral growth, a library of metabolic modulators was screened for activity against MeV using an in vitro infection model. Results showed that Molidustat, a pharmacological inhibitor of Prolyl-Hydroxylase Domain (PHD) enzymes, inhibits MeV infection in a Hypoxia-Inducible Factor (HIF)-dependent manner. We then tested the antiviral effect of Molidustat in organotypic cultures of hamster cerebellum. Molidustat induced the hypoxia-response pathway in this ex vivo model as assessed by transcriptomic analysis, and inhibited MeV infection. A similar antiviral effect was observed with Roxadustat and Daprodustat, two PHD enzyme inhibitors chemically unrelated to Molidustat. Finally, we showed that Molidustat inhibits NiV infection in organotypic cultures of hamster cerebellum and lung, thereby validating its effect in the two organs mainly targeted during infection. Taken together, our results provide evidence that pharmacological activation of the hypoxia-response pathway restricts MeV and NiV infections, highlighting HIF-inducing drugs as promising candidates to consider in the development of treatments.