ProHeart® 12, a moxidectin extended-release injectable formulation for prevention of heartworm (Dirofilaria immitis) disease in dogs in the USA for 12 months

Abstract

Background The efficacy of an extended-release injectable moxidectin (0.5 mg/kg) suspension (ProHeart® 12) (PH 12) in preventing the development of Dirofilaria immitis in dogs for 12 months was investigated in laboratory and field studies in the USA. Methods In each of two laboratory studies, 20 dogs ≥ 12 months of age were randomly allocated to receive a subcutaneous injection of saline or PH 12 on Day 0 and were then inoculated with 50 D. immitis third-stage larvae (L 3 ) on Day 365. All dogs were necropsied ~ 5 months post-inoculation for adult worm counts. The field efficacy study included dogs ≥ 10 months of age from 19 veterinary clinics in the USA treated with either 20 monthly doses of Heartgard® Plus (HG Plus) (296 dogs) or two doses of PH 12 (297 dogs) on Days 0 and 365. Efficacy was determined on Days 365, 480 and 605 using adult HW antigen and microfilaria testing to assess adult HW infection. Results PH 12 was 100% effective in preventing HW disease in all three of these studies. In the laboratory studies, no PH 12-treated dogs had any adult HWs, whereas all control dogs in both studies had adult HWs [geometric mean, 30.2 (range, 22–37) for Study 1 and 32.6 (22–44) for Study 2]. In the field study, all dogs treated with PH 12 tested negative for adult HW infection on all test days (Days, 365, 480 and 605), whereas four dogs receiving HG Plus (positive control) tested positive for HWs during the study (three dogs on Day 365 and one dog on Day 480). All four dogs treated with HG Plus that subsequently tested positive for HWs during the field study were from the lower Mississippi River Valley region, where HW resistance to macrocyclic lactone preventives has been confirmed to occur. PH 12 was significantly better than HG Plus in preventing heartworm disease in the field study ( P = 0.0367). PH 12 was well-tolerated in both laboratory and field studies. Conclusions A single dose of ProHeart® 12 was 100% effective in preventing heartworm disease in dogs for a full year in both laboratory and field studies.

Preventive efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of Heartgard® Plus or Interceptor® Plus against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs

“…The presence of microfilaremia in this dog after receiving an ML for 11 consecutive months strongly supports that this dog was infected with a ML-resistant D. immitis strain [17,18]. Another recent clinical field study [19] which was also conducted in heartworm-endemic regions of the USA, including the LMRV, showed that moxidectin in an extended-release injectable formulation (ProHeart ® 12; Zoetis) provided 100% heartworm prevention in 236 dogs compared to the 98.8% efficacy provided in the 218 dogs treated monthly with Heartgard ® Plus. Of the four Heartgard ® Plus dogs that were positive for D. immitis antigen in that study, three were also positive for D. immitis microfilariae with confirmed monthly compliance; this also supports the likelihood that these dogs were infected with an ML-resistant strain of D. immitis.…”

Efficacy of semi-annual therapy of an extended-release injectable moxidectin suspension and oral doxycycline in Dirofilaria immitis naturally infected dogs

“…ProHeart ® 12 and ProHeart ® SR-12 are brand names of the same extended-release microsphere formulation of moxidectin, the former being marketed in the USA and the later in Australia, Japan, southeast Asia and Brazil. Recently published studies report the efficacy of a single administration of injectable moxidectin at 0.5 mg/kg (1 ml/20 kg) by subcutaneous (SC) injection as a heartworm preventative and safety of 1×, 3× and 5× the dose every six months for three treatments in normal beagles beginning at six months of age and as high as 5× the use rate in reproducing animals, ivermectin-sensitive dogs, and heartworm-positive dogs [16,22].…”

“…Moxidectin was selected for testing here primarily due to its higher intrinsic potency against filarial nematodes when plasma concentrations provide a longer parasite exposure to the drug compared with other ML, including against ML-resistant heartworm strains [ 16 – 18 ]. Pharmacokinetic characteristics of moxidectin, including its high distribution in lipid tissues, reduced metabolism, and long half-life, contribute to its accumulation and high potency [ 18 , 19 ].…”

Safety of an extended-release injectable moxidectin suspension formulation (ProHeart® 12) in dogs

“…Given the comparability between the PH 6 PV profile and that of PH 12 internationally, that owner non-compliance continues to be an issue with monthly-use heartworm preventative products, and that the once-yearly dose interval for PH12 provides inherently superior compliance, Zoetis elected to seek approval for marketing of PH 12 in the USA. The safety objectives for PH 12 studies outlined in this article and in McTier et al [1] were extended as feasible to elucidating the origin and incidence of hypersensitivity-related responses if any should be observed.…”

“…At the site of injection, the tissue response and the morphologic characteristics of degrading microspheres were carefully evaluated for the type and character of inflammation. Due to the anticipated low incidence of these reactions, the study of McTier et al [1] was doubled in size with hope that hypersensitivity-related reactions might be observed and more carefully described.…”