Adeno-associated virus-vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease.

Abstract

BACKGROUND: A treatment of chronic kidney disease (CKD)-associated anemia in cats is needed. SB-001 is an adeno-associated virus-vectored (AAV)-based gene therapeutic agent that is administered intramuscularly, causing the expression of feline erythropoietin. HYPOTHESIS/OBJECTIVE: We hypothesized that SB-001 injection would lead to a sustained increase in PCV in cats with CKD-associated anemia. ANIMALS: Twenty-three cats with International Renal Interest Society (IRIS) Stage 2 to 4 CKD-associated anemia were enrolled at 4 veterinary clinics. METHODS: In a prospective clinical trial, cats were treated with 1 of 3 regimens of SB-001 (Lo 1.2&#x2009;&#xd7;&#x2009;10genome copies [GCs] on Day 0; Lo&#x2009;&#xb1;&#x2009;Hi [supplemental 2nd dose of 3.65&#x2009;&#xd7;&#x2009;10GC on Day 42]; Hi 3.65&#x2009;&#xd7;&#x2009;10GC IM on Day 0) and followed for 70&#x2009;days. RESULTS: A response to SB-001 at any time between Day 28 and Day 70 was seen in 86% (95% confidence interval 65, 97%) of all cats. There was a significant (P&#x2009;<&#x2009;.003) increase in PCV from Day 0 to Day 28 (mean increase 6&#x2009;&#xb1;&#x2009;6 percentage points [pp]; n&#x2009;=&#x2009;21), Day 42 (8&#x2009;&#xb1;&#x2009;9&#x2009;pp; n&#x2009;=&#x2009;21), Day 56 (10&#x2009;&#xb1;&#x2009;11&#x2009;pp; n&#x2009;=&#x2009;17), and Day 70 (13&#x2009;&#xb1;&#x2009;14&#x2009;pp, n&#x2009;=&#x2009;14). Twelve cats were hypertensive at baseline, 4 of which developed encephalopathy during the study. An additional 6 cats became hypertensive during the study. CONCLUSIONS AND CLINICAL IMPORTANCE: Results of this study suggest that SB-001 therapy represents a suitable single injection treatment that can address nonregenerative anemia in cats with CKD. It was generally well tolerated; however, hypertension and encephalopathy developed in some cats as previously described in association with erythropoiesis-stimulating agent therapy.