U.S. Study Demonstrates Positive Effect of Settle® on Endometrial Cups

22 November 2022

Napanee, Ontario, Canada – NovaVive Inc. announces that data from a study with its immunotherapy for the treatment of equine endometritis – Settle® - has been presented at the American Association of Equine Practitioners (AAEP) Annual Convention in San Antonio, TX. The study, “Decreased equine chorionic gonadotropin secretion following hysteroscopic-guided injection of an immunomodulator”, was conducted by researchers at the Gluck Equine Research Center at the University of Kentucky in collaboration with Rood & Riddle Equine Hospital and was presented by Dr. Maria Schnobrich (Rood & Riddle).

Endometrial cups are specialized placental tissues that invade the uterine lining and secrete the hormone equine chorionic gonadotropin (eCG). This hormone results in the prolonged suppression of estrus and false pregnancy in the mare. Pregnancy loss after the development of endometrial cups often leads to the inability to breed mares back for the remainder of the breeding season. To date, no treatment has been found effective in the early reduction/elimination of endometrial cups following pregnancy loss.

In this study, pregnancy was established in nine mares (n=9) before PGF2a-induced abortion was performed at 45 days of gestation. Ten days later, hysteroscopic-guided injection of either treatment (6ml of Settle diluted and extended to a 20ml volume with LRS; n=5) or placebo (LRS; n=4) occurred, with mares randomly assigned into groups. Treatment involved intra-endometrial injection (1ml/endometrial cup, with any excess volume being injected peripherally into the endometrial stroma surrounding the cups). Blood was obtained prior to hysteroscopy, in addition to weekly post-treatment to measure eCG as a marker of endometrial cup viability, and this continued for eight weeks. In follow-up research, a regimen of two injections of a larger dose of Settle one week apart was shown to significantly improve outcomes and the majority of treated returned to heat. Further research is planned to validate these outcomes.

Hysteroscopic-guided injection of the immunomodulator MCWF (Settle®) led to a significant reduction of eCG concentration in comparison to placebo-treated mares. This reduction in eCG concentration was most pronounced at seven days following treatment, with a diminished response noted throughout the remainder of the study. Return to cyclicity could not be assessed under the confines of this study, as mares were treated in late fall of Central Kentucky, and therefore became acyclic due to winter anestrus. Researchers have determined that further research is merited to determine the clinical ramifications of this decrease in eCG concentrations following treatment with the immunomodulator MCWF. 

In other research studies, Settle has proven effective for persistent breeding-induced endometritis (PBIE), for the production of uterine nitric oxide, as an anti-inflammatory in susceptible mares, for pathogenic endometritis, as a non-antibiotic antibacterial in mares with uterine infection, for post-partum endometritis and for improving fertility in the mare.

Settle is manufactured using the NovaVive Mycobacterium cell wall fraction (MCWF) technology. It is approved in the USA, Australia, New Zealand and UAE as an aid in the treatment of equine endometritis caused by Streptococcus zooepidemicus, the hardest to treat cause of the disease. When administered by IV injection or intrauterine (IU) infusion, Settle stimulates the mare’s immune system to fight the infection.

About NovaVive Inc.

NovaVive is a private company founded in July, 2014. The Company has an advanced veterinary immunotherapeutic platform based on mycobacterium cell wall fraction (MCWF) technology with 5 regulator-approved products in the USA. One formulation has been developed as an anticancer therapy in dogs and horses. Other formulations have demonstrated the capability of reducing the reliance on antibiotics in the treatment of bacterial diseases of horses and cattle or effectively treating viral equine respiratory disease.

For more information, please contact Graeme McRae (Graeme.McRae@NovaVive.ca) or Jennifer Shea (Jennifer.Shea@NovaVive.ca).

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