Novel niclosamide prodrug shows promise against canine osteosarcoma

A small feasibility study recently published in the American Journal of Veterinary Research tested an intravenous (IV), modified niclosamide stearate prodrug therapeutic (mNSPT) in client-owned dogs with naturally occurring osteosarcoma and found encouraging pharmacokinetics and survival signals that support further trials. The formulation achieved consistent plasma exposure of both the prodrug and released niclosamide, and treated dogs had longer-than-expected times to metastasis and overall survival in this small group. These results are preliminary but suggest the approach is worth additional study.

What the drug is and why it matters

Niclosamide is an old antiparasitic with documented anticancer activity in laboratory models, but its clinical use for cancer has been limited by poor solubility and bioavailability. The authors developed a stearate prodrug packaged as nanoparticles for IV infusion so that the active drug is released in the bloodstream. That approach raises systemic niclosamide levels to concentrations that exceed those needed to kill osteosarcoma cells in vitro while offering a path to scalable IV dosing.1

Related: A new tool treating canine osteosarcoma

Key results veterinarians should know

Ten dogs were enrolled in the feasibility trial; all underwent tumor resection and received 4 cycles of carboplatin as part of standard care. Seven dogs went on to receive up to 4 weekly infusions of mNSPT at 10 mg/kg. Pharmacokinetic analysis showed a mean peak plasma concentration of approximately 135 µg/mL for the prodrug and 23 µg/mL for released niclosamide, with terminal half-lives of approximately 4.6 hours and 3.2 hours, respectively. Among the 7 treated dogs, the median time to metastasis was approximately 510 days, and the median overall survival was about 632 days. Three treated dogs survived beyond 4 years. The authors emphasize these are small, nonrandomized observations and that some dogs developed metastases before they could receive mNSPT.1

Safety and infusion precautions

Infusion-related effects included transient liver enzyme elevations, episodes of severe panting, fever, and 1 emergency cooling event. Hepatopathy was usually transient. Based on the study experience, practical steps for clinics considering involvement in future trials or compassionate use programs include the following1:

• Monitor temperature and respiratory rate closely during and for several hours after infusion, and be prepared to slow or stop the infusion if signs develop.
• Have cooling measures, oxygen, and emergency protocols in place for rapid intervention.
• Obtain baseline and serial hepatic panels and consider more frequent monitoring in the first 1 to 2 weeks after infusion.

Next research steps

The paper is clear that the feasibility study is an early step and that several specific research efforts are needed before broader clinical use should be considered. The authors call for the following next steps:

Dose-finding study to determine the maximum tolerated dose

The authors recommend an expanded dose-finding clinical trial in dogs to determine the true maximum tolerated dose of mNSPT. This is a prerequisite for designing larger efficacy trials and for translating the dosing to human studies.

Larger randomized efficacy trial in dogs

If a safe dose is established, the authors state that a much larger, randomized, prospective phase 3 clinical trial in dogs is needed to corroborate the survival and metastasis delay signals seen in this small feasibility cohort. This would address biases inherent in historical comparisons and small sample sizes.

More complete pharmacokinetic and exposure sampling

The feasibility study was limited to brief pharmacokinetic sampling (2 hours) because of logistics with client-owned dogs. The authors note that more extensive pharmacokinetic sampling and analysis will be necessary to fully characterize exposure, metabolism, and interpatient variability. Those data will help link exposure to both efficacy and toxicity.

Confirm tumor-level drug delivery and target engagement

Although the nanoparticle design is intended to increase tumor uptake, the authors point out that this remains a theoretical benefit in the current work. Future studies should attempt tumor-level confirmation, such as tumor sampling, imaging approaches, or other measures, to demonstrate drug delivery to cancer tissue and confirm pharmacodynamic effects.

Safety mitigation and infusion optimization

Given the infusion-related events observed (rapid-onset panting, hyperthermia, and transient hepatopathy, including 1 life-threatening hyperthermia event), the authors suggest that safety strategies be explored. Those include evaluating infusion rate, premedication regimens, prophylactic hepatoprotectants, and clearly defined stop or dose-reduction criteria in dose-finding work. The team also began using a prophylactic liver supplement during the trial and notes that further work is needed to define best practices.

Translation planning for human trials

The authors explicitly frame the dog model as a translational, large-animal platform. They propose that, after dose-finding and randomized canine efficacy trials, the data could be used to inform human clinical trial planning.

Takeaway

The study shows that an IV niclosamide prodrug can reach potentially therapeutic plasma levels and produce promising survival observations in a very small group of dogs. The signal is encouraging enough to justify dose-finding and randomized trials, but wider clinical adoption will require larger controlled studies and clearer tumor-target engagement data.

Reference

1. Eward WC, Pavic K, Spasojevic I, et al. Novel niclosamide stearate prodrug therapeutic shows potential efficacy against naturally occurring canine osteosarcoma in a clinical feasibility study. Am J Vet Res. 2025;87(1):ajvr.24.06.0176. doi:10.2460/ajvr.24.06.0176