Vanda Pharmaceuticals Sues FDA Over Tradipitant Hearing Delay – A Misplaced Battle?

This past week, Vanda Pharmaceuticals filed a federal lawsuit accusing the FDA of unlawfully delaying a hearing on the company’s new drug application (NDA) for tradipitant in gastroparesis. According to Fierce Biotech, the dispute stems from a Complete Response Letter (CRL) the FDA issued in September 2024 rejecting tradipitant as a gastroparesis treatment. Vanda contends the agency “generally disregarded” its evidence, and is now blaming FDA bureaucracy and mass layoffs for stalling the hearing. However, an examination of the facts suggests Vanda’s legal aggression is largely misdirected. The FDA’s cautious stance appears justified by the clinical data: the pivotal Phase 3 trial failed to meet its primary endpoint, and the company is left relying on post-hoc analyses to claim efficacy, which is not a substitute for a positive trial result.

Tradipitant and Gastroparesis: The Clinical Background

Gastroparesis is a chronic stomach motility disorder often marked by severe nausea and vomiting. Vanda’s investigational drug, tradipitant (an NK1-receptor antagonist), was tested in diabetic and idiopathic gastroparesis patients. The key Phase 3 trial (ClinicalTrials.gov NCT04028492) randomized 201 adults (about half diabetic, half idiopathic) to tradipitant 85 mg vs. placebo twice daily for 12 weeks. The primary endpoint was the change from baseline in daily nausea severity at 12 weeks. Secondary endpoints included other gastroparesis symptoms and patient-reported outcome measures.

The trial did not meet its primary endpoint. In the full intention-to-treat (ITT) analysis, the difference in nausea reduction between tradipitant and placebo was not statistically significant (P = .741)​. In fact, the overall results showed no significant improvement on nausea severity or other major symptoms. According to FDA briefing materials and Vanda’s own publications, both the primary and secondary endpoints failed to reach significance​. Vanda’s press release and a Healio report acknowledge that “the drug failed to meet statistically significant change in nausea severity at 12 weeks vs. placebo”​. These negative findings were the basis for the FDA’s CRL.

• Primary endpoint missed: Tradipitant did not significantly outperform placebo on nausea reduction at 12 weeks (P = .741).
• Secondary endpoints missed: Other symptom scores likewise showed no statistical benefit over placebo​.
• Post-hoc analyses only: Vanda performed subgroups and sensitivity analyses (e.g. patients with high blood levels of drug or excluding certain “confounders”) that showed some improvement​. However, these were not pre-specified endpoints, and the official trial data remained negative.

Because the registered primary outcome was negative, the trial is conventionally considered “failed.” Vanda’s scientists point out that in post hoc subsets (for example, patients with adequate drug exposure) tradipitant appeared to reduce nausea significantly​. But regulatory agencies are very clear: post-hoc or exploratory findings cannot replace a prospectively powered success. The FDA expects sponsors to present all trial data, not just cherry-picked favorable subsets. As the FDA guidance states, submissions must include “all data or information relevant to an evaluation of…effectiveness” and avoid “selecting only those sources that favor a conclusion of effectiveness.” Any conflicting evidence must be explained by a compelling scientific rationale. Vanda’s reliance on post-hoc signal is precisely the sort of selective evidence that regulators warn against.

Regulatory Standards: When One Trial Fails

FDA’s drug approval standard under the U.S. Food, Drug, and Cosmetic Act requires “substantial evidence” of effectiveness, typically meaning at least two adequate and well-controlled trials each convincing on its own. In practice, the FDA may accept a single trial only if it is exceptionally persuasive and is backed by confirmatory evidence. But in this case, tradipitant’s lone Phase 3 trial produced a non-significant primary result. Under these rules, that trial generally does not qualify as adequate evidence on its own.

Key FDA guidelines reinforce this approach:

• FDA has long held that substantial evidence usually means two positive trials​, or one trial plus “convincing” confirmatory data​.
• A negative primary outcome is usually regarded as inconclusive: experts advise that a failed primary endpoint generally warrants additional trials (with better design or power) rather than reinterpreting existing data. In fact, Pocock and Stone’s NEJM review “The Primary Outcome Fails – What Next?” (2016) emphasizes that missing a primary endpoint should prompt new studies, not substitution by post-hoc findings.
• FDA guidance explicitly warns sponsors to present all data. Trials may be questioned if negative overall results are explained away by excluding unfavorable subsets without strong justification.

Furthermore, the FDA’s own Good Review Practices (GRPs) underscore that reviewers follow documented best practices – focusing on consistency, transparency, and rigor. These internal policies help ensure each application is handled fairly and methodically, not arbitrarily slowed. The agency pointed out that Vanda’s request involves 15,000 pages, including new analyses not in the original NDA, which justifies thorough review under GRPs.

In sum, the regulatory framework suggests that FDA’s request for additional data and its cautious timetable are not arbitrary delays but adherence to standard procedures. A single failed pivotal trial simply does not meet the substantial-evidence bar. According to these criteria, the CRL was scientifically grounded.

When a Primary Outcome Fails

Statisticians and regulators agree: if a trial misses its primary outcome, the conservative path is to consider the study negative (or at best inconclusive) and plan further research. Pocock and Stone’s NEJM review makes this clear. They argue that a non-significant primary result generally means the experiment didn’t prove efficacy; turning to retrospective subgroups or alternative endpoints without a new trial risks false-positive “findings.” In practical terms, a missed endpoint should lead to redesigning studies or confirming any hints of effect in fresh data. Simply reanalyzing the same data to “find” significance is discouraged.

FDA guidance mirrors this stance. Even when one trial shows some favorable signal, the agency demands that confirmatory evidence come from independent sources (for example, a second trial or external data). Confident conclusions require evidence that is not retrospectively cherry-picked. In Vanda’s case, the company essentially trimmed its data after the fact (excluding patients and focusing on those with higher drug exposure) to claim a positive result​. By FDA and statistical standards, that strategy is insufficient. It falls short of the clear, prospectively defined success needed to approve a new treatment.

The Lawsuit and Vanda’s Claims

Vanda’s lawsuit is technically about FDA’s timing: the company alleges the FDA is unlawfully delaying a regulatory hearing on its NDA and related disputes. According to Fierce Biotech, FDA told Vanda it would not schedule the hearing until September 2025 because of the case’s complexity, the new material submitted, and even unrelated litigation and staff layoffs​. Vanda responded by suing, accusing the FDA of stonewalling it and even blaming the agency’s Commissioner and hiring cuts.

In parallel, Vanda is fighting on multiple fronts: it has also challenged FDA rules on its insomnia drug, on clinical holds for other tradipitant studies, and more. The Fierce article notes that Vanda has pressed FDA to hold a hearing within 120 days of its January 2025 request, as the company believes is its right.

However, all these battles circle back to the core issue: tradipitant’s failed data. The CRL that triggered the hearing request was grounded in the negative phase 3 results. In public statements, Vanda’s CEO complained that FDA “generally disregarded” the evidence — but that “evidence” was largely the same trial data and post-hoc arguments that regulators found unconvincing​. The FDA’s position is that the application needed additional study, in line with scientific norms.

A Misplaced Blame

It’s understandable that Vanda is frustrated: developing new drugs is costly, and delays eat into patents and investor patience. But blaming the FDA’s procedures overlooks the science. The data from the major gastroparesis trial simply didn’t demonstrate clear efficacy. In drug development, a failed trial is a standard setback, not usually a basis for litigation. Lawsuits over process cannot overcome the fact that the trial was negative by its own primary analysis.

Regulatory experts would likely say that calling for more trials is the correct outcome. As FDA guidance and statistical authorities emphasize, when a primary endpoint is missed, one doesn’t put lipstick on the dataset to make it pass. Instead, one either finds a new, adequately powered study design or gathers stronger confirmatory evidence. Vanda’s focus on legal maneuvers and after-the-fact data trimming comes across as deflecting from this core reality.

In the meantime, the FDA is merely following its structured review timelines and good practice guidelines. Delays stem from legitimate reasons (volume of material, outside litigation, workforce changes), not from any conspiracy to stall Vanda unfairly.

Ultimately, Vanda’s case serves as a reminder that science should drive decision-making, even amid disputes. The trial evidence—supported by FDA and statistical guidance—points to one conclusion: traditionpitant’s efficacy was not established by the trial as conducted. Vanda may see a silver lining in exploratory data, but regulators are right to hold the company to proven standards. Suing over process, in this instance, appears like a costly distraction from the real task: generating reliable clinical proof for tradipitant.

References:

• FDA guidance “Demonstrating Substantial Evidence of Effectiveness With One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence” (2023)
• FDA guidance “Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products “ (2019)
• Carlin et al (2024) The Efficacy of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Phase 3 Randomized Placebo-Controlled Clinical Trial, Clin. Gastroenterol. Hepatol.
• Pocock & Stone (2016) The Primary Outcome Fails - What Next?  NEJM
• FDA internal “Good Review Practice: OND Review Management of INDs and Marketing Applications for Nonprescription Drug Products “
• FDA internal ““Good Review Practice: Statistical Review Template”