Molidustat in the Management of Nonregenerative Anemia in Feline Chronic Kidney Disease
Sponsored by Elanco
In the Literature
Schmidt F, Ringeisen H, Fent G, Langston C, Collins R, Charles S. Effectiveness and long-term safety of repeated oral administrations of molidustat in the management of anemia associated with chronic kidney disease in cats. J Vet Intern Med. 2026;40(1):aalaf079. doi:10.1093/jvimsj/aalaf079
The Research ...
In cats, nonregenerative anemia related to chronic kidney disease (CKD) is common, especially as the disease progresses to International Renal Interest Society (IRIS) stages 3 and 4.1 Anemia may contribute to disease progression by reducing oxygen delivery to the kidneys and can cause weakness, lethargy, and reduced appetite.1 The IRIS guidelines recommend starting treatment when packed cell volume (PCV) is <25% or is persistently between 25% and 28% for >1 month; however, traditional options (ie, human recombinant erythropoietin and darbepoetin) have known risks, including pure red cell aplasia, iron deficiency, hypertension, and polycythemia.1,2
Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, increases endogenous erythropoietin production by inhibiting hypoxia-inducible factor alpha (HIFα) hydroxylation and degradation.1 This study evaluated effectiveness and safety of molidustat in client-owned cats with CKD-related anemia.
This multicenter study included a 28-day randomized, double-masked, placebo-controlled phase, followed by a 20-week unmasked continuation phase. Enrollment criteria included cats diagnosed with anemia (PCV <28%) associated with CKD based on historical data and baseline serum creatinine >1.8 mg/dL. Comorbidities had to be considered stable.
Cats were administered either an oil-based oral suspension of molidustat sodium at 5 mg/kg (0.2 mL/kg) daily or a placebo and were monitored on days 7, 14, 21, and 28 via hematology and body weight, as well as blood pressure and physical examination on days 14 and 28 and serum chemistry and urinalysis on day 28. In addition, owners completed quality-of-life scoring on days 0 and 28.
Once completing the initial 28-day effectiveness and safety phase, the study was unmasked, and all cats (either on molidustat or placebo) with PCV <28% continued to the unmasked safety continuation phase and received molidustat for ≤4 additional 28-day cycles, with a procedural 7-day pause between each cycle. Safety and effectiveness assessments were monitored periodically throughout.
Seventy-five cats (molidustat, n = 40; placebo, n = 35) completed the initial effectiveness and safety phase. In the initial phase, 68% of cats treated with molidustat achieved success (ie, ≥4% point increase in hematocrit, overall 25% increase in hematocrit, or combination of both) on day 28 as compared with 17% in the placebo group. Mean hematocrit increased by 5.25 points in the molidustat group as compared with decreasing by 0.21 points in the placebo group. There was no significant difference in the rate of adverse effects or euthanasia from progression of CKD between groups. These results confirmed molidustat’s ability to safely stimulate production of erythrocytes in client-owned anemic cats with CKD.
Thirty-two cats per group continued on into the unmasked safety continuation phase. Treatment success per cycle ranged from 43% to 71% across timepoints during the continuation phase. The most frequently reported adverse event was emesis (34.4% of all adverse events observed), which is common in cats with CKD. There was no evidence that any adverse events, including serious ones (ie, diabetic ketoacidosis, adenocarcinoma of the palate, pancreatitis), were related to molidustat. The authors concluded that prolonged and repeated administration of molidustat to anemic cats with CKD was safe when given alone or in combination with medications often necessary for CKD or its comorbidities over a period of 6 months.
... The Takeaways
Key pearls to put into practice:
Molidustat was shown to be safe and effective in the management of anemia in CKD cats at a daily dose of 5 mg/kg as an oil-based oral suspension.
Molidustat was well-tolerated across repeated 28-day cycles (with a 7-day pause between cycles) and remained effective over 6 months.
Although molidustat addresses anemia, its impact on underlying CKD progression is unknown and warrants further study.
The study population included cats with advanced CKD and numerous comorbidities, making evaluation of results inherently complex but representative of field conditions.
Unlike the continuous use of traditional erythrocyte-stimulating agents (ie, human recombinant erythropoietin and darbepoetin), which can lead to adverse effects such as pure red cell aplasia, iron deficiency, hypertension, and polycythemia,1,2 the long-term oral use of molidustat in cats did not result in any of these complications.
Varenzin™-CA1 (molidustat oral suspension) is conditionally approved by the FDA for the control of nonregenerative anemia associated with CKD in cats. Conditional approval is granted to drugs demonstrating a reasonable expectation of effectiveness and with a proven record of safety so that they may be used for treatment while further data is collected to provide substantial evidence of effectiveness.3
Indication
Varenzin-CA1 is indicated for the control of nonregenerative anemia associated with chronic kidney disease (CKD) in cats.
Important Safety Information
For oral use in cats only. Keep this drug, including used syringes, out of reach of children. Wash hands immediately after use. In case of accidental ingestion, seek medical advice immediately. Women who are pregnant or may become pregnant should administer the product with caution. Varenzin-CA1 should not be administered to cats that are pregnant, lactating or intended for breeding or to cats with known hypersensitivity to molidustat. Use with caution in cats with a history of seizures and in cats predisposed to thromboembolic disease. Hematocrit (HCT) or packed cell volume (PCV) levels should be monitored regularly as polycythemia may result from use of Varenzin-CA1. Varenzin-CA1 has not been evaluated in cats less than 1 year of age. The most common adverse reactions included vomiting, increases in systolic blood pressure and mild transient increase in serum potassium. For full prescribing information call 1-888-545-5973 or visit www.elancolabels.com/us/varenzin.
PM-US-26-0730
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