As described in the peer-reviewed journal BMC Veterinary Research, ranevetmab is a PETized™ monoclonal antibody (mAb) that inhibits the activity of canine nerve growth factor (NGF). Nexvet is developing ranevetmab as a treatment to control pain associated with canine osteoarthritis.
As a PETized mAb, ranevetmab is “100% species-specific”, meaning it has been designed to be recognized by the canine immune system as “native”, reducing the likelihood of an adverse “immunogenic” immune reaction in patients.
A pivotal field safety and efficacy study of ranevetmab met its primary endpoint as agreed under protocol concurrence with the U.S. FDA's Center for Veterinary Medicine: a statistically significant benefit over placebo, 28 days after a single subcutaneous injection of ranevetmab, as assessed by owners using a validated pain scoring protocol.
Nexvet and global animal health company Virbac have signed a collaboration and distribution agreement based on an equal profit-share in territories outside the United States and Canada, where Virbac will be ranevetmab’s distributor. Nexvet will retain sole distribution rights within the United States and Canada.
In 2015, Nexvet received notification from the United States Adopted Name (USAN) Council that it had approved the generic name “ranevetmab” for NV-01, its former name.
Ranevetmab inhibits the activity of nerve growth factor (NGF). NGF is elevated in the joints of dogs with osteoarthritis, and is produced by a variety of cells. It acts on pain-sensing nerve fibers to increase their excitability and increase the sprouting of new nerve fibers into inflamed tissues. Human mAbs targeting NGF have been extensively studied in humans through to Phase 3 clinical studies and have been shown to be effective in managing osteoarthritic pain in patients.
In a proof-of-concept study, ranevetmab was given to nine client-owned dogs with chronic lameness due to osteoarthritis and was shown to reduce canine brief pain inventory (CBPI) pain scores, with a duration of action of at least four weeks. CBPI is an owner assessment tool for measuring pain severity and pain interference that is recognized by the FDA. This study’s data was published in the peer-reviewed American Journal of Veterinary Research. Ranevetmab was well tolerated in all of the dogs.
A randomized, placebo-controlled study in 26 client-owned dogs also confirmed that ranevetmab could significantly reduce pain scores at two and four weeks following a single administration. This study used both CBPI and the Client Specific Outcome Measures (CSOM), another owner assessment tool recognized by the FDA. The magnitude of the effect seen following a single injection of ranevetmab was comparable to that observed in the literature with daily administration of non-steroidal anti-inflammatory drugs (NSAIDs) at two and four weeks using CBPI. This study was published in the peer-reviewed journal BMC Veterinary Research in April 2015. Once again, ranevetmab was well tolerated in all patients.
Nexvet received positive results from a pivotal safety and efficacy study of ranevetmab. The study met its primary endpoint as agreed under protocol concurrence with the Center for Veterinary Medicine (CVM) at the U.S. Food and Drug Administration (FDA). The primary endpoint achieved was a statistically significant (p<0.05) improvement over placebo in the assessed level of pain as measured using changes in Client-Specific Outcome Measures (CSOM) score between enrolment and day 28. Additionally, ranevetmab was found to be safe and well-tolerated with no significant adverse safety signals observed in the study.
Clinically meaningful magnitudes of benefit and statistically significant differences over placebo were also achieved for the majority of the secondary endpoints measured in the study. These included pain assessments measured using the validated pain scoring protocols CSOM and CBPI (Canine Brief Pain Inventory) at various points in time. Collectively, the results of this study constitute a substantial body of efficacy data that Nexvet intends to use as the basis of its planned submissions for marketing authorizations in both the U.S. and Europe.
This pivotal, multi-center, placebo-controlled, randomized, double blind study was conducted at 12 sites (6 in the U.S. and 6 in Europe). Protocol concurrence was received from the FDA CVM in August 2014. The final number of dogs enrolled in the study was 262, with dogs randomly assigned to treatment or placebo on a 2:1 ratio. Dogs participating in the study received a subcutaneous injection of NV-01 once per month for three months. Nexvet plans to publish the final study report in a peer-reviewed journal in due course.
A placebo-controlled multi-site field safety and efficacy study evaluated various doses and dosing regimens of ranevetmab in 176 dogs. In March 2016, Nexvet announced the results of this study further supported ranevetmab's efficacy and safety profile.
You may find at this link a presentation summarizing the clinical studies of ranevetmab, with particular focus on the design and outcomes of its pivotal efficacy and field safety study. This presentation was given to an audience of 242 veterinarians at the American College of Veterinary Internal Medicine (ACVIM) Forum, in June 2016.
The treatment of chronic pain in dogs
The U.S. canine pain market is currently dominated by several NSAIDs, which accounted for over 83% of pain medication sales in 2015. NSAIDs are often given as daily medications, and owner compliance with long-term daily dosing is a recognized issue, which Nexvet believes would be addressed by a monthly dose administered by a veterinarian.
NSAIDs account for the largest number of adverse drug events reported to the United States Food and Drug Administration (FDA), including vomiting, gastrointestinal bleeding, diarrhea and liver and kidney toxicities. We believe that the limitations of NSAIDs create a significant commercial opportunity for the development of a novel, long-acting treatment for chronic pain that has comparable efficacy to NSAIDs but without their adverse events.
Between 93% and 97% of 390 veterinarians in a proprietary survey reported they would use a product such as ranevetmab for the treatment of chronic pain in dogs.