Answers to frequently asked questions—

The therapeutic Tin-117m particles in Synovetin OA™ are suspended within a colloid, and following injection into the joint, more than 99% are retained within the joint. After decaying to harmless, inert tin, the particles are transported to nearby lymph nodes and removed from the body. The mode of action of Synovetin OA™ involves no chemical or metabolic processes occurring, which is why Synovetin OA™ is considered a device.

Tin-117m emits discrete (0.3 mm radiation range), low-energy (158 keV maximum) therapeutic conversion electron energy. Particles are retained in the canine joint space following injection. This gives it distinct benefits in canine OA, including optimal duration at the synovial target site due to a long half-life and a long-lasting therapeutic effect—up to 1 year with just 1 intra-articular injection.

Synovetin OA™ targets synovitis, the inflammation that precedes radiographic OA and drives the development of chronic degenerative joint disease. Synovetin OA™ breaks the inflammatory cycle that causes progressive joint damage by eliminating pro-inflammatory macrophages (the source of inflammation) and activated synoviocytes (the source of synovial hyperplasia).

Patient response to Synovetin OA™ will vary depending on the stage of OA. In a clinical trial of dogs with grade 1 or 2 (radiographic) elbow OA, 75% (9/12) improved at one month when compared to the baseline Canine Brief Pain Inventory values (CBPI). Many dogs were reported to have responded within a week or sooner.

There have been no head-to-head comparisons of Synovetin OA™ and NSAIDs for clinical effectiveness. NSAIDs were developed for acute pain use, not the management of a long-term, chronic disease; hence there are no long-term studies for NSAIDs, unlike Synovetin OA™. Synovetin OA™ can be used for cases of OA in which dogs are refractory to NSAIDs or there are safety concerns with NSAID use. In clinical trials, there were no clinically significant local or systemic adverse effects associated with treatment with Synovetin OA™. Synovetin OA™ can also be used in conjunction with NSAIDs as part of a multimodal treatment plan.

Extensive data points were collected at study baseline and 1, 3, 6, 9, and 12 months. Data such as force plate gait analysis, clinician lameness exam scores, pet owner assessments using the validated Canine Brief Pain Inventory instrument (CBPI), radiographs, CT, fused PET/MRI imaging data, CBC, chem screen, joint fluid analysis, additional medication usage, and a number of other parameters were collected and statistically reviewed.

The efficacy of Synovetin OA™ was demonstrated in a multi-center study. Sites included Gulf Coast Veterinary Specialists, Louisiana State University School of Veterinary Medicine, and University of Missouri College of Veterinary Medicine. 3 validation metrics confirm formidable and durable treatment effect:

Clinician’s lameness assessment: Dogs with grade 1 & 2 elbow OA given the label dose had a mean reduction in overall lameness score from baseline at each post-treatment interval—1, 3, 6, 9, and 12 months. There were statistically significant improvements seen at 9 and 12 months. Dogs with grade 3 elbow OA had a mean reduction in lameness score from baseline at 3, 6 and 9 months.

Forced plate gait analysis: 82% of dogs with grade 1 & 2 elbow OA treated with the label dose showed significant increase in peak vertical force and/or vertical impulse after just 1 injection. Measurements were taken at 1, 3, 6, 9, and 12 months. Treatment Success was defined as an improvement in peak vertical force and/or mean vertical impulse during follow-up visits compared to baseline.

Canine brief pain inventory tool: Pet parents reported 12 months of sustained efficacy in dogs with grade 1 & 2 and grade 3 elbow OA treated with the label dose. In grade 1 & 2 OA, the mean pain severity score and pain interference score both showed statistically significant improvement at all time intervals compared to baseline. Furthermore, there was statistical agreement between clinician and pet parent assessments.

No radionecrosis was seen either when administered appropriately or when mis-administered (inadvertent periarticular injection); nor was it seen in the laboratory rat model, where much larger dose-to-weight radiation doses were delivered. Furthermore, deliberate misadministration in rats showed no necrosis.

In the 5 normal dog study, no differences were detected between treated and untreated joints. No damage to any joint adnexal structures were found by Alison Bendele, DVM, PhD, DACVP, of Bolder BioPATH, Inc., Boulder, CO, in her analysis of both histologic sections from the 5 normal dog study and in earlier laboratory rat studies (carried out to 10 weeks).

Laboratory, excretion, and dosimetry results were unremarkable for all 74 dogs treated (97 elbows). Furthermore, no significant adverse effects were noted and no unforeseen safety issues were identified by either pet parents or medical personnel.

Based on the results of the clinical study program, therapeutic conversion electron energy is limited to the injected joint only. The Tin-117m particles are small enough to be phagocytized by synovial macrophages but large enough to avoid leakage outside the joint.

Yes, as with any medical isotope there are some special instructions for administering Synovetin OA™. Exubrion provides comprehensive training to hospitals for the proper handling and use of Synovetin OA™. There is no need to quarantine the dog after the injection and there is no significant excretion of Tin-117m, so interactions with treated dogs are largely unrestricted compared to those for cats treated with Iodine-131 for feline hyperthyroidism.

Yes, following measurement of activity at 1m and documentation that levels are below established release guidelines.