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. 2023 Nov-Dec;37(6):2200-2210.
doi: 10.1111/jvim.16900. Epub 2023 Oct 17.

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

Shelly L Vaden  1 , Allison R Kendall  1 , Jonathan D Foster  2 , Heidi L New  3 , Jane S Eagleson  4 , Jacky L May  5 , Anne M Traas  5 , Matthew J Wilson  5 , Beth H McIntyre  6 , Christian J Hinderer  7 , Lauren K Olenick  5 , James M Wilson  7
Affiliations

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

Shelly L Vaden et al. J Vet Intern Med. 2023 Nov-Dec.

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 × 109 genome copies [GCs] on Day 0; Lo ± Hi [supplemental 2nd dose of 3.65 × 109 GC on Day 42]; Hi 3.65 × 109 GC IM on Day 0) and followed for 70 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 < .003) increase in PCV from Day 0 to Day 28 (mean increase 6 ± 6 percentage points [pp]; n = 21), Day 42 (8 ± 9 pp; n = 21), Day 56 (10 ± 11 pp; n = 17), and Day 70 (13 ± 14 pp, n = 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.

Keywords: AAV; cats; red blood cells; renal disease.

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Conflict of interest statement

Shelly Vaden serves as Associate Editor for the Journal of Veterinary Internal Medicine. She was not involved in the review of this manuscript. Anne Traas, Jacky May, Lauren Olenick and Matt Wilson are employees and shareholders of Scout Bio, Inc, the company that is developing SB‐001. Jim Wilson and Christian Hinderer are also shareholders in Scout Bio. Beth Oman is a paid consultant for Scout Bio. James M. Wilson is a paid advisor to and holds equity in iECURE, Scout Bio, Passage Bio, and the Center for Breakthrough Medicines (CBM). James M. Wilson also holds equity in the former G2 Bio asset companies. James M. Wilson has sponsored research agreements with Amicus Therapeutics, CBM, Elaaj Bio, FA212, former G2 Bio asset companies, iECURE, Passage Bio, and Scout Bio, which are licensees of Penn technology. Christian J. Hinderer holds equity in Scout Bio and a former G2 Bio asset company. James M. Wilson and Christian J. Hinderer are inventors on patents that have been licensed to various biopharmaceutical companies and for which they might receive payments.

Figures

FIGURE 1
FIGURE 1
Individual PCV (%) values of all cats. Shaded areas represent the laboratory reference range of 28% to 53%. (A) Lo cats administered a dose of 1.2 × 109 GC on Day 0; (B) Lo ± Hi cats administered a dose of 1.2 × 109 GC on Day 0 that were not administered a supplemental dose; (C) Lo ± Hi cats administered a dose of 1.2 × 109 GC on Day 0 followed by a supplemental dose of 3.65 × 109 GC on Day 42; (D) Hi cats administered a dose of 3.65 × 109 GC on Day 0.
FIGURE 2
FIGURE 2
Histogram of cats in each cohort achieving the primary (PCV in reference range), secondary (PCV increased ≥5 percentage points), or either goal at Day 42, Day 70, or at any time from Day 28 to Day 70. *The last value was carried forward for cats with final data points before the listed day.
FIGURE 3
FIGURE 3
(A) Kaplan‐Meier survival curve all cats by cohort; (B) Kaplan‐Meier survival curve by response determined any time from D28 to D70, primary goal; (C) Kaplan‐Meier survival curve by response determined any time from D28 to D70, either primary or secondary goal; (D) Kaplan‐Meier survival curve by response determined at Day 42, primary goal; (E) Kaplan‐Meier survival curve by response determined at Day 42, either primary or secondary goal.
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