Mode of Action Information
Why is Synovetin OA™ considered a device?
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.
Why was Tin-117m selected for use in canine OA?
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.
How does Synovetin OA™ work to treat OA?
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).
Effect on OA Pain and Inflammation
How long will it take to see pain relief following a Synovetin OA™ injection?
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.
How does Synovetin OA™ compare with NSAIDs regarding effectiveness?
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.
What effectiveness and safety criteria were measured in the clinical studies?
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.
What percentage of client-owned study dogs responded favorably to the label dose of Synovetin OA™?
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.
Safety of Synovetin OA™
Was radionecrosis observed in the studies?
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.
Does Tin-117m negatively affect chondrocytes?
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).
Were there any adverse events related to the Tin-117m in Synovetin OA™?
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.
Do the particles in Synovetin OA™ migrate into tissue outside the treated joint?
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.
Are there special instructions the veterinary hospital needs to follow to administer Synovetin OA™?
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.
Can a dog treated with Synovetin OA™ be released from the clinic the same day as administration?
Yes, following measurement of activity at 1m and documentation that levels are below established release guidelines.
Clinical Study Information
Why were canine elbows the focus of Synovetin OA™ clinical trials?
The elbow was selected because it is arguably the most complex and challenging canine OA joint for treatment of degenerative joint disease and has fewer options available for treatment than the hip and stifle. Canine elbow OA affects up to 20%+ of dogs, many at a young age, causing a lifetime of pain and immobility and a poor quality of life.
How many studies in total have been conducted with Synovetin OA™?
In dogs, Exubrion has completed 4 studies covering 74 dogs and 97 treated elbows, including:
- 5 normal dog safety and autoradiography study
- 12-month client dog safety and efficacy study in which the subjects presented with naturally-occurring Grade 1 or 2 elbow OA
- 12-month client dog study in which the subjects had Grade 3 elbow OA and both elbows were treated, if indicated
- 12-month client dog study in which a previously injected elbow was reinjected
In addition, there have been 7 preclinical studies in more than 340 laboratory rats.
Dosing and Administration
What is the recommended dose of Synovetin OA™?
Synovetin OA™ is dosed by weight, with the specific dose customized to the individual patient. The maximum joint injection for dogs 110 lbs and larger is 3 millicuries (mCi) (0.75–1.5 cc). For dogs less than 110 lbs, the clinic is instructed to administer Synovetin OA™ following guidelines in the product dosing chart. The maximum total one-time dose is 6 mCi to treat 2 joints.
What is the retreatment dose?
Synovetin OA™ can be readministered at a 12-month interval and at the same dose (providing the patient has not changed weight).
How does the administering hospital receive Synovetin OA™ and what is its storage life?
Synovetin OA™ will be sent via FedEx in a specially marked package for the specific patient from Theragenics, the manufacturing facility located in Buford, Georgia.
Synovetin OA™ should be administered on the designated treatment day. However, if necessary, the dose can be administered the day before or the day after the prescribed treatment day without changing the dosage administered.
What is the licensing process for prescribing Synovetin OA™ and is it state-specific?
A veterinary facility will need a radioactive materials (RAM) license to handle Synovetin OA™.
If a facility already has a RAM license for Iodine-131, it will need an amended RAM license that includes Tin-117m, which is a simpler process than obtaining the original RAM license. For a facility without a RAM license, the requirements to register Tin-117m are less stringent than those for Iodine-131.
Exubrion has an extensive complimentary RAM Navigator Program in place to help a practice amend an existing RAM license or apply for a new RAM license to handle Tin-117m. More information is available from your Exubrion sales representative.
Information for Pet Parents
What is the benefit of Synovetin OA™ for pet parents?
Synovetin OA™ is a safe and effective treatment for long-term relief of the pain and inflammation associated with chronic OA.
- Just one injection gives up to one full year of pain relief.
- The treatment can be repeated yearly.
- It is easy for pet parents to comply with treatment because there is no need for multiple injections or daily dosing of medication.
- There are no clinically significant local or systemic adverse effects.
What specific discharge instructions do pet parents need?
After the Synovetin OA™ procedure, the treated dog can go home the same day.
- The dog will not need to be restrained, and pet parents can let him or her return to whatever level of activity he or she is comfortable with.
- As with any medical procedure, there are some simple release instructions to follow at home.
- Contact your Exubrion sales representative for information about release instructions.
Synovetin OA™ delivers sustained OA pain relief.1
Synovetin OA™ provides targeted, non-systemic therapy.2
- Data on file, Exubrion Therapeutics.
- Donecker JM, Fox SM. Safety and effectiveness of Synovetin OA™: Results of three randomized trials evaluating treatment of naturally occurring canine elbow osteoarthritis. Exubrion Therapeutics, July 2019.