A prospective, randomized, double-blind, placebo-controlled multisite, parallel-group field study in dogs with osteoarthritis conducted in the United States of America evaluating bedinvetmab, a canine anti-nerve growth factor monoclonal antibody.

OBJECTIVE: Bedinvetmab, a fully canine anti-nerve growth factor monoclonal antibody, was evaluated in dogs for control of osteoarthritis-related pain in a study conducted to support registration in the USA. STUDY DESIGN: Randomized, double-blind, placebo-controlled, multicenter, parallel-group study. ANIMALS: General practice client-owned dogs with osteoarthritis (n = 272). METHODS: Dogs were block randomized 1:1 to placebo (saline, n = 137) or bedinvetmab (n = 135; 0.5-1.0 mg kg-1) administered subcutaneously, once monthly. The primary end point, day 28 Canine Brief Pain Inventory (CBPI) treatment success (TS), required pain severity score (PSS; 0-10) decrease ≥1 and pain interference score (PIS; 0-10) decrease ≥ 2. CBPI TS rates [and number needed to treat (NNT)], change in scores [and standardized effect size (ES)], change in quality of life (QoL) and bedinvetmab half-life were calculated. RESULTS: Significant (p < 0.05) improvement with bedinvetmab over placebo occurred (days 28, 42, 56, 84) for CBPI TS. Of cases evaluable for day 28 CBPI TS (placebo, n = 131; bedinvetmab, n = 128), success rates were 36.6% and 47.4%, respectively (p = 0.0410) (NNT, 9.3; PSS and PIS ES, 0.3). CBPI TS increased after the second dose in both groups, plateaued for bedinvetmab at day 42 and decreased for placebo beginning day 84. Day 84 NNT (4.3), PSS (0.4) and PIS (0.5) showed continued improvement with monthly dosing. After the first dose, mean (± standard deviation) bedinvetmab half-life was 19.1 (8.3) days. Adverse events were similar between groups and not considered treatment-related. There was a significant effect of bedinvetmab versus placebo on all CBPI components (PIS, PSS, QoL). CONCLUSIONS AND CLINICAL RELEVANCE: These results corroborated those previously reported and provide further support of safety and effectiveness of bedinvetmab (0.5-1.0 mg kg-1) administered subcutaneously at monthly intervals to dogs for control of osteoarthritis-related pain.

VANGUARD®crLyme: A next generation Lyme disease vaccine that prevents B. burgdorferi infection in dogs.

Lyme disease, a public health threat of significance to both veterinary and human medicine, is caused by the tick (Ixodes) transmitted spirochete, Borreliella burgdorferi. Here we report on the immunogenicity and efficacy of VANGUARD®crLyme (Zoetis), the most recent canine Lyme disease vaccine to be approved by the United States Department of Agriculture. VANGUARD®crLyme is a subunit vaccine consisting of outer surface protein A (OspA) and a recombinant outer surface protein C (OspC) based-chimeric epitope protein (chimeritope) that consists of at least 14 different linear epitopes derived from diverse OspC proteins. The combination of OspA and the OspC chimeritope (Ch14) in the vaccine formulation allows for the development of humoral immune responses that work synergistically to target spirochetes in both ticks and in mammals. Immunogenicity was assessed in purpose-bred dogs. A two-dose vaccination protocol resulted in high antibody titers to OspA and Ch14 and vaccinal antibody reacted with 25 different recombinant OspC variants. Efficacy was demonstrated using an Ixodes scapularis -purpose bred dog challenge model. Vaccination with VANGUARD®crLyme provided protection against infection and prevented the development of clinical manifestations and histopathological changes associated with Lyme disease.

Field safety study of VANGUARD®crLyme: A vaccine for the prevention of Lyme disease in dogs.

Here we report the results of a large-scale pre-license safety study in which two serials of VANGUARD®crLyme, a vaccine for canine Lyme disease, were tested in its target population (dogs) under the conditions of its intended use. Six-hundred and twenty dogs, from three distinct geographic regions of the United States were enrolled in this study with each receiving two doses of vaccine by subcutaneous injection 3 to 4 weeks apart. Approximately one-third of the dogs were of minimum age (≤8 weeks of age) to meet regulatory requirements. Safety was evaluated by observation of local and systemic reactions for at least 10 days after each vaccination. Abnormal health events (AHEs) occurred at low frequencies and no serious AHEs were observed. The results demonstrated that VANGUARD®crLyme is safe for use in healthy dogs 8 weeks of age or older.

Efficacy of a novel oral formulation of sarolaner (Simparica™) against five common tick species infesting dogs in the United States.

The efficacy of a single oral treatment with sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was evaluated against five tick species known to infest dogs in the United States. A total of 10 laboratory studies, two against each species, were conducted using adult purpose-bred mongrels or Beagle dogs. In each study, 16 dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 unfed adult Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis or Rhipicephalus sanguineus ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs were treated with a placebo or a sarolaner tablet providing a minimum dose of 2 mg/kg. Tick counts were conducted 48h after treatment and after each subsequent weekly re-infestation. There were no treatment-related adverse reactions during any of the studies. Dogs in the placebo-treated group maintained tick infestations throughout the studies. Geometric mean live tick counts were significantly lower (P≤0.0001) in the sarolaner-treated group compared to the tick counts in the placebo group at all timepoints. Treatment with sarolaner resulted in ≥99.6% efficacy against existing infestations of all five tick species within 48h. The efficacy against weekly post-treatment re-infestations of all tick species was ≥96.9% for at least 35 days after treatment. Thus, a single dose of sarolaner administered orally at the minimum dosage of 2mg/kg, resulted in excellent efficacy within 48h against existing tick infestations, and against weekly re-infestations for 35 days after treatment. These studies confirmed that administration of the minimum dose of sarolaner will provide rapid treatment of existing infestations and give at least one month of control against re-infestation by the common tick species affecting dogs in the US.

Efficacy of sarolaner in the prevention of Borrelia burgdorferi and Anaplasma phagocytophilum transmission from infected Ixodes scapularis to dogs.

The efficacy of sarolaner (Simparica™, Zoetis) to prevent transmission primarily of Borrelia burgdorferi and secondarily of Anaplasma phagocytophilum from infected wild-caught Ixodes scapularis to dogs was evaluated in a placebo-controlled laboratory study. Twenty-four purpose-bred laboratory Beagles seronegative for B. burgdorferi and A. phagocytophilum antibodies were allocated randomly to one of three treatment groups: placebo administered orally on Days 0 and 7, or sarolaner at 2mg/kg administered orally on Day 0 (28 days prior to tick infestation) or on Day 7 (21 days prior to tick infestation). On Day 28, each dog was infested with approximately 25 female and 25 male wild caught adult I. scapularis that were determined to have prevalence of 57% for B. burgdorferi and 6.7% for A. phagocytophilum by PCR. In situ tick counts were conducted on Days 29 and 30. On Day 33, all ticks were counted and removed. Acaricidal efficacy was calculated based on the reduction of geometric mean live tick counts in the sarolaner-treated groups compared to the placebo-treated group for each tick count. Blood samples collected from each dog on Days 27, 49, 63, 77, 91 and 104 were tested for the presence of B. burgdorferi and A. phagocytophilum antibodies using the SNAP(®) 4Dx(®) Plus Test, and quantitatively assayed for B. burgdorferi antibodies using an ELISA test. Skin biopsies collected on Day 104 were tested for the presence of B. burgdorferi by bacterial culture and PCR. Geometric mean live tick counts for placebo-treated dogs were 14.8, 12.8, and 19.1 on Days 29, 30, and 33, respectively. The percent reductions in mean live tick counts at 1, 2, and 5 days after infestation were 86.3%, 100%, and 100% for the group treated with sarolaner 21 days prior to infestation, and 90.9%, 97.1%, and 100% for the group treated with sarolaner 28 days prior to infestation. Geometric mean live tick counts for both sarolaner-treated groups were significantly lower than those for the placebo group on all count days (P<0.0001). There were no adverse reactions to treatment with sarolaner. Transmission of B. burgdorferi to all eight placebo-treated dogs was confirmed by positive antibody (6 of 8 dogs), PCR (7 of 8 dogs), and/or culture (7 of 8 dogs). Similarly, transmission of A. phagocytophilum was confirmed by the presence of antibodies in four placebo-treated dogs. In contrast, treatment with a single dose of sarolaner prevented transmission of B. burgdorferi from infected ticks to dogs infested 21 or 28 days after treatment as demonstrated by negative antibody, PCR, and culture results. Prevention of transmission of A. phagocytophilum was demonstrated by negative antibody results in all sarolaner-treated dogs.

Comparative speed of kill of sarolaner (Simparica) and afoxolaner (NexGard) against induced infestations of Ctenocephalides felis on dogs.

BACKGROUND: Fleas are the most common ectoparasite infesting dogs globally. The many possible sequellae of infestation include: direct discomfort; allergic reactions; and the transmission of pathogens. Rapid speed of kill is an important characteristic for a parasiticide in order to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea infestation cycle. In this study, the speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica) against fleas on dogs was evaluated and compared with afoxolaner (NexGard) for 5 weeks after a single oral dose. METHODS: Twenty-four dogs were randomly allocated to treatment with a single oral dose at label rate of either sarolaner (2 to 4 mg/kg) or afoxolaner (2.5 to 6.8 mg/kg) or placebo, based on pretreatment flea counts. Dogs were combed and live fleas counted at 8, 12 and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs. RESULTS: There were no adverse reactions to treatment. A single oral dose of sarolaner provided ≥98.8% efficacy (based on geometric means) within 8 h of treatment or subsequent weekly re-infestations of fleas to Day 35. By 12 h, fleas were virtually eradicated from all dogs, with only two fleas recovered from a single sarolaner-treated dog on Day 7; efficacy was 100% at all other time points. Significantly greater numbers of live fleas were recovered from afoxolaner-treated dogs at 8 h on all days and at 12 h on Days 28 and 35 (P < 0.05). CONCLUSIONS: In this controlled laboratory evaluation, sarolaner had a significantly faster speed of kill against fleas than afoxolaner. This was noticeably more evident towards the end of the treatment period. The rapid and consistent kill of fleas within 8 to 12 h after a single oral dose of sarolaner over 35 days indicates that this treatment will provide highly effective control of flea infestations, relief for dogs afflicted with flea allergy dermatitis, and should reduce the risk of flea-borne pathogen transmission.

Comparative speed of kill of sarolaner (Simparica and fluralaner (Bravecto) against induced infestations of Ctenocephalides felis on dogs.

BACKGROUND: Fleas are the most common ectoparasite infesting dogs globally and cause direct discomfort, induce allergic reactions, and transmit pathogenic agents. Rapid speed of kill is an important characteristic for a parasiticide in order to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea life cycle. In this study, the speed of kill of a novel, orally administered isoxazoline parasiticide, sarolaner (Simparica), against fleas on dogs was evaluated and compared with fluralaner (Bravecto) over a 3-month period. METHODS: Based on pretreatment flea counts, 24 dogs were randomly allocated to treatment with oral sarolaner at the label rate (2 to 4 mg/kg), once a month for 3 months, or oral fluralaner (25 to 50 mg/kg), once per label directions, or placebo. Dogs were combed and live fleas counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 14, 29, 44, 59, 74 and 90. Efficacy was determined at each time point relative to counts for placebo dogs. RESULTS: There were no adverse reactions to treatment. Three monthly doses of sarolaner provided ≥97.6 % efficacy (based on arithmetic means) within 8 h of treatment or subsequent weekly re-infestations of fleas for 3 months. By 12 h, fleas were eradicated from all dogs (100 % efficacy). Significantly greater numbers of live fleas were recovered from fluralaner-treated dogs at 8 h on Days 74 and 90 (P ≤ 0.0043) when efficacy (based on arithmetic means) was only 80.7 and 72.6 %, respectively. CONCLUSIONS: In this controlled laboratory evaluation, sarolaner had a significantly faster speed of kill against fleas than fluralaner at the end of its claimed treatment period. The rapid and consistent kill of fleas within 8 to 12 h after monthly oral doses of sarolaner indicates that this treatment will provide rapid and highly effective control of flea infestations, and suggests that it will provide relief for dogs suffering from flea allergy dermatitis, and should reduce the risk of flea-borne pathogen transmission.

Comparison of effectiveness of cefovecin, doxycycline, and amoxicillin for the treatment of experimentally induced early Lyme borreliosis in dogs.

BACKGROUND: While Koch's postulates have been fulfilled for Lyme disease; causing transient fever, anorexia and arthritis in young dogs; treatment of sero-positive dogs, especially asymptomatic animals, remains a topic of debate. To complicate this matter the currently recommended antibiotic treatments of Lyme Disease in dogs caused by Borrelia burgdorferi require daily oral administrations for 31 days or longer, which makes non-compliance a concern. Additionally, there is no approved veterinary antimicrobial for the treatment of Lyme Disease in dogs in the USA and few recommended treatments have been robustly tested. In vitro testing of cefovecin, a novel extended-spectrum cephalosporin, demonstrated inhibition of spirochete growth. A small pilot study in dogs indicated that two cefovecin injections two weeks apart would be as efficacious against B. burgdorferi sensu stricto as the recommended treatments using doxycycline or amoxicillin daily for 31 days. This hypothesis was tested in 17-18 week old Beagle dogs, experimentally infected with B. burgdorferi sensu stricto, using wild caught ticks, 75 days prior to antimicrobial administration. RESULTS: Clinical observations for lameness were performed daily but were inconclusive as this characteristic sign of Lyme Disease rarely develops in the standard laboratory models of experimentally induced infection. However, each antibiotic tested was efficacious against B. burgdorferi as measured by a rapid elimination of spirochetes from the skin and reduced levels of circulating antibodies to B. burgdorferi. In addition, significantly less cefovecin treated animals had Lyme Disease associated histopathological changes compared to untreated dogs. CONCLUSIONS: Convenia was efficacious against B. burgdorferi sensu stricto infection in dogs as determined by serological testing, PCR and histopathology results. Convenia provides an additional and effective treatment option for Lyme Disease in dogs.