Originally posted by Chemical & Engineering News
“The two of us stood gazing at the gleaming rows without any idea that it was nearly all useless and that the days of the old medicines were nearly over. Soon they would be hustled into oblivion by the headlong rush of the new discoveries.”
So wrote country veterinarian James Herriot about the bottles in his practice’s drug dispensary during the 1930s. Although the discoveries he referred to—human antibiotics, sulfa drugs, and steroids—would change his practice immensely, they were not designed for animals.
Even today, animal-specific drugs are uncommon, especially in the areas of cancer and pain. And that’s true even though about 65% of U.S. households own at least one pet, which adds up to 86 million cats and 78 million dogs, among other animals, according to the American Pet Products Association.
The $7.5 billion-per-year animal health market is dominated by large companies, such as the former Pfizer business Zoetis. Although most of these firms have big pharma ties, they often don’t target diseases but rather viruses, parasites, and infections, often for livestock. Seeing a gap, a new breed of biotech start-ups is developing small-molecule and biologic drugs for pets by leveraging the science around human medicines.
“The companion animal space is where the human biotech space was maybe 30 years ago,” says Richard Chin, founder and chief executive officer of California-based Kindred Biosciences. He and others in the emerging field hope that it reaches a similar level of success.
Enabling the growth of animal health are the right tools, accessible therapies, and seemingly few regulatory hurdles. But the fledgling firms are just starting to work with regulators and have yet to see if pet owners will buy more modern, and expensive, medicines.
In recent years, the declining cost of manufacturing and a more receptive investor base have allowed human and animal health to converge. Pfizer’s $2.2 billion spin-off of Zoetis in 2013 sparked interest and, in turn, helped a handful of start-ups quickly go public. But the most important driver has been the shifting attitudes of pet owners.
Eighty years ago, Herriot, who tended mostly to farm and working animals, was shocked when Mrs. Pumphrey christened him “uncle” to her pampered Pekingese Tricki Woo. Today, 95% of pet owners consider their animals a family member, according to a 2015 Harris Poll. In addition to spending $1 billion per year on costumes and gifts, pet owners are willing to pay hefty sums for veterinary care.
Many animal biotech company founders are pet owners who came to realize, after losing furry companions, that treatments are limited. Not just softhearted animal lovers, they leveraged impressive pedigrees in human biotech to recruit former regulators and executives from traditional animal health firms. As a result, their companies quickly identified licensable products, advanced development, and started navigating the regulatory scene.
Around 2009, investor Steven St. Peter began exploring how to apply the human drug development approach to pet medicines. Now, the company he heads, Kansas-based Aratana Therapeutics, has nearly 20 small molecules and antibodies in the pipeline. “We hope next year to have three products through the Food & Drug Administration and three through the U.S. Department of Agriculture,” St. Peter says.
Since 1913, USDA has overseen animal vaccines as well as biologics that act through the immune system. FDA handles small molecules and other drugs. Either way, regulators require that animal drugs are safe and show substantial evidence of effectiveness. Drug manufacturing also must meet quality standards, but USDA’s are not necessarily as rigorous as FDA’s requirements.
In contrast with human drugs, animal drugs can be tested immediately in the target species. Clinical trials are smaller, usually consisting of a “pilot” study of as little as a few dozen animals followed by a “pivotal” study of a few hundred for full approval.
Aratana has full USDA approval for a canine anti-CD20 antibody for treating B-cell lymphoma, which is the target of the human drug Rituxan. And the company has conditional approval for its anti-CD52 antibody against T-cell lymphoma in dogs, which allows it to enter the market while pivotal trials are run.
In 2014, Aratana struck a $45 million deal to license four immunotherapies from the human biotech firm Advaxis, which had done preclinical testing in dogs. Aratana hopes to win approval of a treatment for canine osteosarcoma by 2016.
Working with small molecules, Aratana is developing capromorelin to stimulate appetite and grapiprant for osteoarthritis-related pain in dogs. It licensed both compounds from Japan’s RaQualia Pharma. And to treat postsurgical pain in dogs, Aratana licensed a bupivacaine liposome injectable from Pacira Pharmaceuticals.
Translating a therapy from human to animal has to make medical and commercial sense. For instance, preclinical testing for human small-molecule drugs can generate a substantial amount of valuable data. If collected in dogs, those data are “almost directly applicable to form the basis of a safety submission for regulatory approval in animal health,” says Steven Roy, CEO of VetDC.
A spin-off from Colorado State University and its animal cancer research center, VetDC looks to human drug candidates that may have those data but were shelved in development. As a result, it can get compounds for “a good price and move them forward pretty quickly,” Roy says. “Economically, I don’t think we could make the model work to start from scratch.” The firm has a lymphoma drug, Tanovea™-CA1 (rabacfosadine), awaiting FDA approval that came from Gilead Sciences.
Brad Loncar, a private investor and stock pundit who follows and invests in animal health, warns that “there are no shortcuts.” Companies have to take development seriously, and those that think the translation from humans to pets is easy risk failing. For example, he says, “you have to run pilot studies and get dosing right,” because humans and animals respond differently.
There are fewer shortcuts to tempt companies developing pet antibody drugs because the firms can’t easily leverage human data. Even if human and animal disease targets are the same, antibodies must be species-specific to be effective and nonimmunogenic. As a result, animal health biotechs all have their own methods for making the required structural changes.
Kindred makes such changes, Chin says, but it “isn’t reinventing the wheel.” It is developing the canine equivalent of the arthritis drug Orencia, the anti-inflammatory Enbrel, and the allergy medicine Xolair.