Guest post by Ingrid R Niesman, MS PhD
While we don’t really know the extent of pain cats actually experience, we do know that they are masters at masking their discomfort, leaving cat parents guessing. This is especially true with arthritis pain. Just like humans, cats’ joints take a lifetime of abuse and display similar arthritic tendencies with age. Humans can avoid suffering with medications and joint replacements. Our cats with chronic osteoarthritis (OA) or degenerative joint disease (DJD) have fewer options.
A new option to control feline pain
In January of this year, the FDA approved the first-in-its-class feline-specific anti-pain medication. Marketed by Zoetis under the trade name Solensia, this monthly injectable treatment is scheduled to arrive in veterinary clinics later this year. This can be game changing for many aging cats. Although there are two NSAIDs (non-steroidal anti-inflammatory drug) approved overseas for cats, none are approved for use in the US. NSAIDs in general are tough on kidneys, making them questionable choices for chronic feline use, even if considered marginally safe.
What is Solensia and why is it different?
Solensia (frunevetmab) is a biologic therapy, as opposed to common medications that are small molecule drugs. A biologic is a protein or lipid molecule derived from natural sources. In the case of Solensia, this therapy is derived from a single rat hybridoma cell clone, something cell engineers call a monoclonal antibody.
Hybridoma cells are a fusion of two reactive immune cells; one that was exposed to a specific reactive protein – in the case of Solensia, nerve growth factor (NGF); the other an antibody producing B-cell. These fusion cells are then selected for the best antibody that “sees” the specific reactive protein, for example NGF, the target of Solensia.
To make this rat antibody safe for cats, the molecule had to be reengineered into a typical feline antibody class, while leaving the part that could neutralize NGF intact. This fully felinized anti-NGF monoclonal antibody is now Solensia.
How does Solensia work?
NGF has two opposing sides to its biological function. On one hand, this protein is critical in the development of brain connections in infancy and neuronal survival in early childhood. But later in adulthood, NGF takes a modulatory role in pain sensations, favoring stimulating rather than suppressing nerve endings.
In order to affect biological processes, a protein like NGF must first bind to another surface protein, enter a cell, be transported to a cell nucleus and communicate that something needs to change in a cell’s current status. Many drugs block, modify or switch this delicate dance of cell signaling in some way. Solensia works by preventing NGF from binding to its membrane receptor – TrkA; and blocking cell entry. No signaling means no pain response from the neuron.
OA and DJD can cause an increase in localized NGF. The cells that keep synovial fluid flowing and cartilage healthy are damaged in OA progression and pump out increasing amounts of NGF. Pain and discomfort ensue.
Will this be effective in treating my cat’s OA or DJD pain?
Effective pain control is one of the biggest conundrums in modern medicine. If a drug works, it can be addictive or lose efficacy over time. Considering the biological role NGF plays in pain modulation, there has been considerable work dedicated to developing therapies that could block its action.
Sadly, early attempts in treating humans with anti-NGF therapies resulted in rapidly accelerating OA or DJD progression and nerve ending damage, especially when combined with NSAIDs. The FDA halted all human clinical trials in 2010. Interest in renewed development occurred when anti-NGF monoclonal antibodies were shown to have significant pain reducing properties for knee and hip OA in human trials.
The good news for cats is that in recent placebo-controlled proof of concept and safety clinical trials of Solensia, cat mobility improved over baseline activity, as reported by home questionnaires. B. Duncan Lascelles, Ph.D, FRCVS, DACVS from North Carolina State University College of Veterinary Medicine and investigator on three of the published Solensia trials, describes the results as dramatic. “In our initial trial, this was the first time I had seen obvious beneficial pain reduction results during the study. In studies of other therapeutics, we get our answer on whether a therapeutic is efficacious when we do the data analysis; but in this study we were seeing obvious signs of pain reduction in patients during the study. Clients reported cats becoming kittens again … jumping back on counters. These same results held up through the next two larger trials.”
In addition to client reported results, investigators used accelerometry data (no, cats do not carry iPhones!) to back up subjective data with precision measurements. Although all cats had some decrease in activity, there were considerable differences between the treated and control cats.
What about safety for my older cat?
Hip and spinal arthritis is mainly a disease of aging felines. Therefore, how will this therapy be tolerated by senior cats? The published data describe a doubling of vomiting issues when cats are injected with Solensia. However overall, cat parents expressed satisfaction with the results on their cat’s response to treatment.
My main concern after reviewing US-lead trials and the European FDA summary is a lack of long-term monitoring for rapid degeneration of joints. Rapidly progressive osteoarthritis (RPOA) is a known condition that increased in incidence in trials of human anti-NGF monoclonal antibodies, particularly when larger doses were given, or NSAIDs were used at the same time. “Obviously we are all aware of and watching for anything similar in cats, but as far as I am aware, the condition of RPOA has never been described in either cats or dogs, and nothing similar has been seen in the Solensia studies,“ said Dr. Lacelles. “This condition, RPOA, may be a unique human pathology.” More data will be collected once Solensia becomes available commercially.
When questioned about chronic use by client cats, Dr. Lascelles raised an interesting point. “Pain adversely affects the entire body, not just the localized site. But once we treat pain, everything gets better – all parts of the body and the pain transmission system all become more normal. Once this happens – once pain is under control – the time between dosing may be able to be lengthened. We are already hearing reports of this from colleagues in the EU where the drug has been in clinical use.”
No daily pills
Pilling a cat daily is daunting for most cat parents, even with pill hiding treats. Dr Lascelles shared with me that he had not appreciated the burden associated with pilling a cat until he had to pill his own cats! A once-a-month injection is a tantalizing option. However, putting your cat in the carrier and driving to the vet office may also be an obstacle for many.
With the US approval of Solensia and the arrival in vet clinics coming soon, now is a good time to evaluate the health of your aging cat. Do you see signs of mobility loss or quality of life declining? If so, contact your veterinarian and discuss what a treatment plan with Solensia could do to improve overall health. Once my cats reach that point, I will be asking the same questions.
Ingrid R. Niesman MS PhD is the Director of the SDSU Electron Microscope Imaging Facility at San Diego State University. She graduated from Utah State University and received her MS from the University of Illinois-Urbana-Champaign. After 30 years of technical electron microscopy, cell biology, neuroscience and infectious disease research, Dr. Niesman completed her PhD in the UK at the University of Sunderland. Her work experience includes time at LSU Medical School, Washington University, UAMS in Little Rock, UCSD, TSRI and a postdoctoral year at CALIBR in La Jolla, CA. She has worked for at least two National Academy of Science members and is credited with over 50 publications. She can be reached at iniesmanphd@gmail.com
