FDA formally refuses to approve Vanda's tradipitant for gastroparesis after protracted regulatory battle

The FDA on March 26, 2026 formally refused to approve tradipitant, Vanda Pharmaceuticals' NK-1 receptor antagonist for the treatment of gastroparesis symptoms, following an unusually contentious 30-month regulatory dispute. The decision, issued by Principal Deputy Commissioner Sara Brenner and published in the Federal Register, denied Vanda's request for a hearing and concluded the proceedings that began with a Complete Response Letter in September 2024.

Tradipitant works by blocking the neurokinin-1 (NK-1) receptor, through which substance P triggers nausea and emesis via the nucleus tractus solitarius. In gastroparesis specifically, NK-1 antagonism may offer a dual mechanism: modulating gastrointestinal motility peripherally while suppressing central nausea signalling. Vanda originally licensed the compound from Eli Lilly and positioned it as a potential first-in-class oral treatment targeting gastroparesis-associated nausea.

The FDA's refusal centred on two deficiencies. First, one of Vanda's Phase III studies failed to demonstrate a statistically significant improvement in nausea severity versus placebo—the application's primary efficacy endpoint. Second, the agency deemed the available safety database inadequate, requesting longer-term data and additional studies. Vanda disputed both conclusions, arguing that a pre-specified pooled analysis of two Phase III trials met the primary endpoint with statistical significance, and that the safety database was sufficient for the proposed indication.

The regulatory timeline between the initial CRL and the final refusal was marked by exceptional friction. Vanda publicly accused the FDA of issuing a "conclusory" CRL more than 185 days past the statutory deadline and subsequently sued the agency for unlawfully delaying a hearing. The FDA cited workforce reductions; Vanda countered that the cuts did not affect scientific reviewers. The dispute included formal hearing requests, competing legal filings, and a brief collaborative pause, before the final refusal brought the process to a close.

Gastroparesis—delayed gastric emptying in the absence of mechanical obstruction—affects an estimated 5 million Americans, with nausea being the most debilitating symptom. The only FDA-approved drug for the condition, metoclopramide, carries a black-box warning for tardive dyskinesia with prolonged use and is limited to 12 weeks of therapy. This leaves patients relying on off-label antiemetics, dietary management and, in severe cases, surgical interventions such as gastric electrical stimulation. The unmet need is substantial, and the failure of tradipitant to reach the market represents a significant setback for the gastroparesis community.

Vanda's broader portfolio offers some counterbalance: the FDA approved its atypical antipsychotic Bysanti (milsaperidone) in February 2026, and motion-sickness drug Nereus in late 2025. At the time of the decision, Vanda had not indicated whether it would pursue further legal action, initiate additional clinical studies, or end the programme.

Sources: Federal Register Decision; Vanda Pharmaceuticals; FDA.