Vanda Pharmaceuticals has failed to persuade the FDA to approve its gastroparesis candidate on the strength of a phase 3 trial that missed its primary endpoint. The biotech came out swinging after the knock-back, accusing the agency of sending a complete response letter that generally disregarded the evidence.
Vanda CEO Mihael Polymeropoulos, M.D., had voiced frustrations with the approval process in the run-up to the PDUFA date, using an earnings call in July to tell investors the FDA was yet to schedule an advisory committee meeting despite the biotech’s “repeated requests.” The agency had told Vanda that it had found deficiencies in its filing but was yet to respond to a request for clarification, Polymeropoulos said at the time.
The FDA’s identification of issues that precluded talks about labeling and post-marketing requirements suggested Vanda’s filing may have been in for a bumpy ride. That suggestion was confirmed Thursday morning when the biotech revealed it had received a complete response letter. Vanda, a company with a history of challenging the FDA, isn’t taking the setback lying down.
“The CRL was conclusory in nature, generally disregarded the evidence provided and instead suggested that Vanda conduct additional studies with a design and duration inconsistent with the advice of key experts in the field and not appropriate based on the scientific understanding and natural course of the disorder,” the biotech said in a statement.
Vanda also took aim at the alleged tardiness of the FDA, stating the agency’s action “was delayed by more than 185 days and fails to satisfy the requirements specified by the Food, Drug and Cosmetic Act.” The biotech said the act requires the regulator to provide either an approval or an opportunity for a hearing within 180 days of submission. In this case, Vanda said, “the FDA failed to do either.”
The biotech plans to continue to pursue marketing authorization for the molecule, the NK-1R antagonist tradipitant and support an expanded access program that it said is serving “several dozen” people. The persistence reflects Vanda’s view that the evidence from across its phase 2, phase 3 and open-label trials supports the use of the drug in the gastric emptying disorder.
Tradipitant was no better than placebo at reducing the severity of nausea across 12 weeks of treatment in Vanda’s phase 3 trial. However, the biotech identified a baseline imbalance of rescue medication use between the treatment arms and some poor compliance with the study drug as a potential cause of the flop. Excluding patients Vanda deemed to be confounders, the study hit its primary endpoint.
Vanda’s inability to get the FDA to approve the drug on the strength of a failed phase 3 further extends a long-running effort to get tradipitant to market. The biotech licensed the molecule from Eli Lilly in 2012 and had paid the drugmaker $5 million in upfront fees and milestones as of the end of 2023. Lilly started a phase 2 trial in alcohol craving in 2006.
The biotech tried—and failed—to establish the molecule in eczema but kept going in other indications. Vanda is planning to file for approval in the prevention of vomiting in motion sickness this year, giving it a second crack at authorization even if it fails to find a way forward in gastroparesis.
Shares in Vanda fell 13% to $4.28 in premarket trading Thursday morning.