A Bernese mountain dog is prepared for radiation treatment of a snout tumor at the Cancer Institute at Manhattan's Animal Medical Center.
Despite landmark advancements in human cancer treatments, oncology therapies for family pets remain woefully behind the curve, much to the chagrin of veterinarians in the field.
The advent of immuno-oncology drugs such as checkpoint inhibitors, which stimulate the immune system to fight cancer, has "added a whole new arsenal of immunotherapies for physicians" on the human side, according to veterinary oncologist Jenna Burton. Other innovations include chimeric antigen receptor T-cell, or CAR-T, therapy, which leverage a patient's own modified cells for treatment, and precision medicine.
Excitement is mounting on the animal side, with veterinary drug developers and researchers seeking to apply similar technologies to companion animals. But the market for animal cancer therapies is difficult to break through, as promising drugs are reallocated for human use, and the price tags can be too high for pet owners.
Dogs contract cancer at about the same rate as humans — about 1 in 4 overall are diagnosed, and about 50% of those are over the age of 10, according to the American Veterinary Medical Association. The AVMA noted that less information is available about cancer in cats, though lymphoma is more common for felines than dogs.
Zoetis Inc.'s small-molecule inhibitor drug Palladia — the first companion animal-specific anti-cancer agent — was approved by the U.S. Food and Drug Administration in 2009 to treat canine mast cell tumors.
Before Palladia, animals were treated exclusively by generic human chemotherapy medicines on an off-label basis, meaning veterinarians adapted human medicines and doses for use in animals even though they were not specifically approved for that indication by the FDA. Off-label use, also called extra-label use by veterinary oncologists, is a common practice among healthcare professionals when only limited treatment options exist.
Other animal cancer treatments include VetDC, Inc.'s recently approved chemotherapy drug Tanovea for canine lymphoma and Merial LLC's conditionally licensed therapeutic melanoma vaccine Oncept.
Veterinary Cancer Society president Timothy Fan, also a professor of veterinary clinical medicine at the University of Illinois at Urbana-Champaign, said the field of veterinary medicine is "wide open" for drug development.
The more options, the merrier
Pharmaceutical companies face an uphill battle when developing cancer therapies for human use — even when drug candidates demonstrate impressive efficacy — due to competition in the marketplace, Fan said. But the same is not true for the animal market, where only a handful of drugs are approved.
"People recognize that the pet industry is exploding across the board," VetDC CEO Steven Roy said. "It cuts across healthcare, insurance, pet products, pet services. So there's a lot of investor excitement in tapping into that."
For example, from 2012 to 2017, investments in pet-related startups increased by a whopping 334% to $291.8 million, according to market data provider Crunchbase. Privately held VetDC, meanwhile, raised about $2.1 million in its most recent disclosed round of growth funding.
Roy noted that the veterinary oncology field is growing at about 13% year over year, and he expects canine cancer treatments in particular to continue to climb. Pet owners are highly motivated to seek new, innovative options for their pets, he added.
The exact number of pets who receive cancer treatment is uncertain, as veterinarians do not have a centralized epidemiology database. According to Global Market Insights, a market research and management consulting company, pet cancer therapeutics account for over 80% of the overall companion animal industry's revenue in North America. Acumen Research reports that the global market will continue to swell at a compound annual growth rate of 10.6% through 2026.
One major barrier for pet owners is the cost of treatment. The hundred-thousand-dollar price tag commonly seen on innovative human medicines would not be feasible for pet owners. The cap, according to Roy, is more in the thousands of dollars. The cost for dogs' chemotherapy treatment typically ranges from $2,000 to $10,000, he said.
"We have many cases of people who are going to do anything they can for their dogs," Roy said. "And others that really make that decision: My dog's old, had a good life, was with us for a long time, and I really don't want to go through this or I can't afford to go through this."
Fan expects pet insurance rates to creep up over the next several years, adding that pet owners tend to prioritize reactionary care rather than preventative treatment.
Because of the cost, human drugs that would work for animals often cannot be adapted for veterinarian use until they reach the generic stage, which can take many years. And drugs found to be effective in animals in early clinical trials will often be deviated for human use.
For instance, Johnson & Johnson and AbbVie Inc.'s Imbruvica was first tested in dogs, but now the targeted blood cancer therapy, which blocks malignant cell signals, costs approximately $148,000 a year.
From humans to dogs, dogs to humans
Rob Rebhun, associate professor and researcher of surgical and radiological sciences at the University of California, Davis Center for Companion Animal Health, said that much can still be learned to create a drug for dogs after a therapy has moved to human trials, but resources can be difficult to come by for development.
Leveraging already-approved human medicines for animals is more common than the other way around, according to Rebhun, but researchers are recognizing that pet dogs could be good models for trialing immunotherapies — especially compared to using mice, which can be immunocompromised and unreliabile predictors for human efficacy.
Dogs that have naturally developed a disease have a normal immune system more closely reflecting that of humans, and pet dogs also share the same environment as humans, Rebhun said. Scientists have a better understanding of the dog genome and biology, and dogs are big enough for biopsies and blood work, unlike cats and smaller companion animals.
This means dogs are ideal candidates to test out drugs — but clinical trials for pets that provide a therapeutic benefit are a sharp contrast from traditional preclinical research for human drugs that would involve breeding dogs or other animals specifically for research, and then sacrificing them for tissue analysis.
Burton, the veterinary oncologist, said that for pet owners, "there's a very fine line between animal research and clinical trials in pets." She emphasized that pets are protected while in clinical trials and overseen by clinical trial review boards and committees, similar to human trials. Burton is an associate professor, researcher and assistant research scientist of surgical and radiological sciences at UC Davis.
For Burton and other veterinary oncologists, clinical trials for pets would ideally benefit both dogs and humans, by protecting dogs' welfare and finding better treatment options for both species.
"A lot of our owners recognize their pets may not benefit, but they're doing it for the greater good and the possibility that this could help other dogs in the future," Burton said.
A robust pipeline
The limited drugs available specifically for animal oncology is not for a lack of research and development, according to Rebhun.
Roy and Fan noted that immunotherapies are a primary source of excitement in the field. Cancer vaccines, which are mostly in preclinical development for human use, and monoclonal antibodies have also generated buzz in animal oncology. Monoclonal antibodies are engineered proteins that can bind to substances in the body including cancer cells.
A labrador uses an underwater treadmill to recover from knee surgery at Manhattan's Animal Medical Center's Cancer Institute.
VetDC is one of the companies adapting failed human medicines for animals rather than re-inventing the wheel, Rebhun said. The company is developing an inhibitor of two proteins that play central roles in cancer growth — PI3kinase, or PI3K, and MTOR — for animal use. The oral inhibitor, VDC-597, is first being tested in dogs with a blood vessel cancer called hemangiosarcoma, and could potentially treat other tumors.
PI3K and MTOR therapies are also in development at Novartis AG and Roche Holding AG's Genentech Inc. for human cancers.
Aratana Therapeutics Inc. is conducting studies on a canine osteosarcoma vaccine live listeria virus, or COVLLV, which has a conditional license from the U.S. Department of Agriculture's Center for Veterinary Biologics. Osteosarcoma, one of the most common cancers in dogs, is a bone cancer typically treated by veterinarians with amputation and chemotherapy.
Both Aratana and VetDC are working with one of the largest animal health companies, Elanco Animal Health Inc., to develop their therapies. Aratana Therapeutics was acquired by Elanco in April 2019 for about $245 million, while at the same time, VetDC signed a partnership to continue developing and commercializing Tanovea.
Rebhun is also testing an inhaled cytokine drug in a phase 1 trial for osteosarcoma and melanoma, another common dog cancer, in canines with advanced-stage disease that has spread to the lungs. Essentially no standard of treatment exists for dogs with these conditions, he said.
The study involves a class of cancer drugs called interleukin therapies and is funded by the National Institutes of Health with the aim of finding ways to reduce side effects and predicting who might benefit from the therapy — that is, which humans might benefit. But Rebhun said the trial could lead to additional possibilities for treating dogs as well. Interleukin therapies, also in early-stage human trials, are another form of immunotherapy.
Meanwhile, Burton is leading a preventative cancer vaccine study in healthy dogs, which could also ultimately treat humans. According to Burton, the vaccine's developer, Arizona State University professor Stephen Johnston, has already worked with the USDA Center for Veterinary Biologics to ensure data from the five-year trial can be used to gain conditional approval for use in dogs.
The vaccine aims to prevent a range of eight common cancers found in dogs.
"The bottom line is two separate vaccines, similar mechanism of action, but one for humans, one for dogs," Burton explained.