Having gone from biotech start-up to industry disruptor in what has seemed the blink of an eye, Nexvet is counting down the months until it changes the vet medicine landscape for good. By Chris Sheedy
FEW DISCOVERIES OR INNOVATIONS have altered the human medical world as decisively as monoclonal antibodies. The fact that particular proteins already existing within our bodies can be cloned then used to specifically target disease-causing proteins or organisms in the body has meant effective medicines with far fewer side effects have been developed for cancer treatment, autoimmune diseases and several other applications.
Monoclonals as a class are generally more specific and safer and have a longer duration and action than traditional small-molecule medicines. It’s no surprise then that they have completely revolutionised how multiple human conditions are treated, and are a massive focus for research and development. So why aren’t they also being used in animals? Some time from 2017, they will be.
Biotechnology company Nexvet, launched in 2010 by biochemists Dr Mark Heffernan and Professor David Gearing, is fast-tracking the testing of monoclonal drugs for use on dogs and cats.
“There has long been a great need for such solutions for companion animals,” says Dr Heffernan, who in 2003 moved from Melbourne to Dublin to launch a business developing human monoclonal antibodies. “Nobody had previously pioneered or focused on the field of monoclonal antibodies for animals. I saw that as an open opportunity. I could take my skills and expertise on the commercial and research side with monoclonals and combine that with the knowledge of one of our co-founders, David Gearing.”
Prof Gearing, now the chief scientific officer of Nexvet, developed a platform of technology called ‘PETisation’, a quick and robust single-step process that takes a monoclonal antibody from one species (say human or mouse) and from that creates a version 100 per cent tailored to another species, say dogs, cats or horses.
“We are the only company in the vet market that can claim at this stage to be 100 per cent capable of such intra-species conversion,” says Dr Heffernan, Nexvet’s CEO. “We have created an opportunity that could have an impact on issues such as pain and atopic dermatitis in dogs and cats, which is poorly served by the current therapies.”
Veterinarian Dr Ralph Webster from Melbourne’s Southpaws Specialty Surgery for Animals has been running tests with Nexvet’s first drug, known as NV-O1. It’s a treatment for chronic pain in dogs, a fully caninised monoclonal antibody that targets a key mediator in the pain pathway in dogs. NV-O1 has successfully completed multiple safety, efficacy, immunogenicity and pharmacokinetic studies. The drug will now be progressed through increasingly larger trials of efficacy in the treatment of osteoarthritic pain in dogs.
Dr Webster’s original trial centred around 11 dogs suffering pain and lameness despite the use of non-steroidals. The dogs were followed over six to 12 weeks, with their volunteer owners not knowing exactly when the drug was administered.
“From the data we received, it looks like the treatment (a single injection) worked very well for four weeks and then started to tail off towards five or six weeks,” says Dr Webster. “The dogs were much less lame and in much less pain. At six weeks their health was still better than at the beginning of the study but not as good as it had been at four weeks.”
“We also didn’t see any side effects, and we know the current medicines in the market can have some serious side effects. All of the dogs in our study had a positive response, so it worked on all of them. Of course, I imagine the drug will not have the exact same magnitude of effect in all dogs. Just like humans, individual dogs will react differently to various drugs.”
Nexvet’s website hosts links to published papers regarding two trials, including Dr Webster’s. These papers can be viewed on Nexvet’s website at www.nexvet.com/products.
Why do these particular monoclonals work so well? It’s because Nexvet’s therapeutics are 100 per cent customised to their target species, Dr Heffernan says. The fact that dogs and cats, as with humans, already have antibodies as part of their immune systems means the body doesn’t recognise Nexvet’s pet-customised antibodies as foreign, as something that needs to be rejected. Finally, the monoclonal is very specific to targets within the animal’s body, rather than taking a scattergun approach and causing ‘collateral damage’.
So what difference are such drugs likely to make in the lives of pet owners and vets? Dr Heffernan says the changes will be noticed on several levels.
“Currently owners are giving their pets non-steroidal drugs that must be taken daily, typically by pill,” he says. “So one simple issue is convenience. It’s easy to forget to give the pill, and it can be difficult to administer a pill. Also, there are quite frequent gastrointestinal side effects—such as ulceration, bleeding and diarrhoea, as well as liver and kidney toxicity—in up to 30 per cent of patients.
“With our product you’d go to the vet once every four to six weeks and get a single injection. Pet owners would see in their animals an improvement comparable to the effect non-steroidals would have but without the long-term issues.”
An advantage for the vets themselves is more frequent contact with the owner and the pet, meaning the pet’s wellbeing, and the pain it has been suffering, is able to be monitored more regularly. The vet is able to check out the existing health problem, and monitor for other issues, during that monthly to six-weekly visit.
“This also means there will be more of an opportunity for vets to educate owners about the wellbeing and general health of their pets, which is a win for everybody—especially the pet,” Dr Heffernan says.
In terms of timeline, the next key point the Nexvet team is looking towards is the end of 2015 when they aim to complete large efficacy and safety studies for NV-O1, essential for regulatory filing. A second product (NV-O2), addressing the current problem of a lack of support for the alleviation of chronic pain in cats, is next in the pipeline, along with others.
“How will we know we’ve succeeded?” asks Dr Heffernan. “Call me again in a couple of years when we hope to have finished major testing, have built the business in the US, and be nearing market launch, in Australia too, and we have the attention of the major animal health companies. The world’s biggest pet care market is in the US—it’s about 40 to 50 per cent of the companion animal market internationally—followed by Europe, Japan and Australia. They’re the four territories we’ll be focused on.”