(Page 3 of 4)
observing and reporting how their pets are responding to treatments. “We have no idea with [laboratory] rats and mice, frankly. They’re caged. It’s a very artificial situation,” Kauffman says. “Dogs are in domestic situations. Their owners are extremely attentive.”
One of the pet owners who volunteered her dog for the Karyopharm study is also the study’s lead investigator, Cheryl London, associate professor of canine medicine at Ohio State University. London noticed the same side effect in her dog, a foxhound named George, that other participants in the study were reporting: the dogs lost their appetites on Karyopharm’s experimental cancer pill, KPT-335. “When my dog quit eating, he quit eating for days,” London says. “It took a long time for his appetite to come back.” (George was suffering from lymphoma and ultimately died of a complication of conventional chemotherapy, London says.)
London has since dropped the dose of KPT-335 being used in the dog trial, which she says has helped alleviate the appetite issues. Karyopharm’s Kauffman says that in addition to running the lymphoma trial at Ohio State, the company is working with Texas A&M’s veterinary school to study KPT-335 in osteosarcoma, a form of bone cancer that strikes children and dogs. The company is also gearing up to test the human version of the drug, KPT-330, in non-Hodgkin’s lymphoma, multiple myeloma, leukemia, and solid tumors.
Kauffman says he was inspired to test Karyopharm’s technology in dogs by London’s success with a cancer pill called toceranib phosphate (Palladia), which was developed by New York-based Pfizer alongside a human version, sunitinib (Sutent). Both drugs inhibit proteins called receptor tyrosine kinases, and London led the charge to test the power of the technology in pet dogs. Toceranib phosphate, which hit the market in 2009, is the first and so far only cancer drug approved by the FDA specifically for dogs. Prior to its approval, veterinarians had no choice but to use the same chemo and radiation drugs given to people.
Sales estimates are hard to come by in veterinary medicine, but Kauffman says he has learned enough about the demand for effective cancer treatments in pets to convince him KPT-335 is worth pursuing. “We do think there’s a market there,” he says. “And the investment required for approval in veterinary medicine is substantially lower than what’s required for humans,” which helps make it feasible for cash-poor startups to pursue the companion-animal market, he adds.
“Science as Serendipity”
For Lexington, MA-based Synta, dog trials have been essential to fine-tuning an emerging class of drugs called heat shock protein 90 (Hsp90) inhibitors. Hsp90 is what’s known as a chaperone protein, says Synta scientist David Proia, because it shuttles thousands of other proteins around inside cells—including some that cause cancer.
In studies, Synta has shown that its lead drug, ganetespib, accumulates in cancerous tissues, but is rapidly cleared out of normal cells, which may help lessen toxicities, Proia says. Determining the best dosing schedule to achieve a response has been challenging, though. So Proia has been working with Ohio State’s London to study what’s called a “pro-drug” of ganetespib—a separate molecule that is converted in the bloodstream to something that’s equivalent to the actual drug.
One of the dogs that participated in the early Synta dog trials at Ohio State demonstrated both the perils and promise of working with canines. The dog, a high-strung Belgian Teruven, was supposed to get a one-hour infusion of the drug into a vein. But he was so frisky that he pulled his catheter out, and the drug ended up going under his skin, London recalls.
Much to London’s surprise, the rowdy dog was the only one in the trial whose cancer responded well to Synta’s drug.
With the help of London, scientists at Synta figured out that giving Synta’s drug outside of the vein completely changes its behavior in the body. “This is science as serendipity,” London says. “To me, the challenge lies in figuring out how … Next Page »