Vanda, FDA Clash Over Animal Testing Requirements
Vanda Pharmaceuticals and FDA are asking a federal judge to resolve a dispute over the agency's partial clinical hold on a yearlong trial of tradipitant for gastroparesis, with the company arguing that FDA's insistence on additional animal toxicity testing violates the FDA Modernization Act 2.0 and the agency defending the hold on both safety and efficacy grounds.
In a 56-page brief filed 10/28, Vanda argues that FDA improperly rejected 11 reports of nonanimal testing studies and continues to treat a nine-month dog toxicity study as a mandatory prerequisite for extended human trials, despite Congress' 2022 legislation recognizing alternative nonclinical testing methods.
FDA, in its 9/30 opposition and cross-motion for summary judgment, argues that the legislation permits sponsors to submit nonanimal testing data but does not require the agency to accept studies that fail to adequately characterize a drug's safety risks.
The agency said it reviewed Vanda's in vitro studies, including liver cell cultures and a four-organ microphysiological system, but determined that studies lasting one to four weeks could not reliably characterize the risks of daily tradipitant exposure over 12 months.
FDA also questioned the studies' limited coverage of potential toxicities, noting that they examined the liver, kidneys, heart and brain, while conventional nonrodent studies permit examination of more than 40 organs and tissues.
Vanda counters that FDA has failed to adequately explain why its nonanimal studies are insufficient and that requiring sponsors to demonstrate that alternatives perform at least as well as a nine-month animal study effectively perpetuates the animal-testing requirement.
The dispute extends beyond toxicology. FDA argues that Vanda's proposed Phase 3 study, Trial VP-VLY-686-3305, is inadequately controlled because it would compare tradipitant with variable standard-of-care treatments in an open-label design.
The agency also cites the failure of Vanda's earlier Phase 3 Trial 3301, involving 200 patients, to demonstrate a statistically significant improvement in gastroparesis symptoms. FDA maintains that the earlier results strongly suggest tradipitant lacks effectiveness for gastroparesis and that the proposed study would not provide a reliable assessment of treatment effects. Vanda disputes the agency's interpretation and argues that its new trial is principally intended to evaluate long-term safety.
The parties also disagree over FDA's reliance on the International Council for Harmonisation's M3(R2) nonclinical safety guidance. Vanda contends that FDA effectively treats the guidance's nine-month nonrodent testing recommendation as a binding requirement, while FDA argues that the guidance is nonbinding and that its clinical hold rests on independently established regulatory grounds.
FDA further points to a 2020 district court decision rejecting Vanda's earlier challenge to a tradipitant clinical hold and argues that the company is barred from relitigating the guidance issue. Vanda maintains that the FDA Modernization Act 2.0 changed the applicable legal framework and permits reconsideration.
The clinical hold case, Vanda Pharmaceuticals Inc. v. FDA, No. 1:26-cv-01443, is pending before judge Amit P. Mehta in the U.S. District Court for the District of Columbia.