Vanda Pharmaceuticals Inc. has filed a complaint against the U.S. Food and Drug Administration after the agency requested an additional nine-month toxicity study in dogs to test the safety of tradipitant, placing the clinical trial for the therapy on hold in the meantime.
Washington, D.C.-based Vanda is refusing to conduct the animal study, saying the partial clinical hold was "illegally imposed," according to a Feb. 5 press release.
Tradipitant is under development to treat the inflammatory skin disorder atopic dermatitis and gastroparesis, a stomach condition that prevents the stomach from properly emptying. Vanda has an eight-week phase 3 study in atopic dermatitis underway and is planning an open-label extension study spanning 12 months for gastroparesis. The drug was purchased by Vanda from Eli Lilly and Co. in 2012.
The FDA's clinical hold bars Vanda from studying the drug in humans for more than 12 weeks until the animal study is completed, meaning the company cannot proceed with the gastroparesis trial as planned. Vanda said the nine-month study in dogs, which would involve euthanasia at the end of the study to analyze tissues, is not scientifically justified and thus "unethical and inhumane."
Beyond the animal rights concerns, the FDA's animal study requirement would delay the "urgently needed" gastroparesis treatment, Vanda said. The condition affects an estimated 6 million Americans. The company argued that the therapy has been shown to be safe in three previous extended test conducted on rats and dogs.
"Vanda believes that we all have an ethical responsibility to reduce, refine and replace animal experimentation to the maximum extent possible," the company said. "While the FDA purports to aspire to the same goals, its actions with respect to tradipitant and its inflexible demand that companies conduct toxicity studies that have been shown to serve little scientific purpose suggest otherwise."
The company has filed a lawsuit asking a federal court to lift the clinical hold and allow the clinical trial to proceed.
Non-negotiable
Last updated in 1997, the FDA's guidance on preclinical safety evaluation for biotechnology-derived pharmaceuticals recommends one to three months of animal dosing, with some cases requiring six months. The guidance also called for relevant animal species according to the drug and condition.
Vanda said tradipitant has been tested in three-month and six-month rat studies, plus a three-month dog toxicity study at doses up to 300 times the intended human equivalent dose. Those studies showed no safety concerns.
"If a company submits information to the FDA to show that further study in humans would be safe based on different information, the FDA is supposed to evaluate the company's proposal and make a case-specific, science-based determination as to whether it agrees," Vanda said. "In Vanda's case, the FDA did not do so. It has instead treated a non-binding recommendation that nine-month non-rodent toxicity studies should be conducted before a drug is studied in humans for longer than three months as a non-negotiable requirement."
According to Vanda, the nine-month toxicity study in non-rodents is "routinely" mandated, despite a lack of scientific evidence supporting such a need. The company called for fellow drugmakers, as well as animal advocacy organizations and members of the scientific community and public, to join in questioning the FDA's outdated guidance on long-term animal studies.
The U.S. Environmental Protection Agency in 2007, for instance, abolished a blanket requirement to conduct 12-month toxicity studies in dogs for pesticide registration, Vanda noted.
"Nine-month dog studies rarely, if ever, identify toxicities that were not already identified in three-month studies," Vanda said in a letter to the FDA.
A questionable approach
Shares of Vanda were down nearly 20% to $20.06 after market close Feb. 6.
Stifel analyst Derek Archila wrote in a Feb. 6 note that Vanda's legal approach to the partial clinical hold was "questionable," adding that conducting the animal study would be "cheap and easy to execute." Archila noted that tradipitant's developmental timeline likely will not be affected, as Vanda may proceed with planned studies as the lawsuit is ongoing.
However, Vanda has a separate product candidate, Hetlioz, for sleep disorder Smith Magenis syndrome, ready to be filed for approval.
"It's certainly not prudent to sue the FDA when you are about to file a [supplemental New Drug Application]," Archila wrote. "So this potentially increases the risk around this program since it would likely need enhanced FDA interaction."
The FDA did not respond to a request for comment as of publication.