Vanda Pharmaceuticals is set to challenge the FDA's rejection of its New Drug Application (NDA) for tradipitant, a neurokinin-1 receptor antagonist, aimed at treating gastroparesis. The FDA's decision, delivered via a Complete Response Letter in September 2024, cited a lack of substantial evidence of efficacy, a conclusion Vanda vehemently disputes.
Disagreement Over Efficacy Evidence
Vanda's NDA included data from two placebo-controlled studies. In Study 1 (152 patients), tradipitant showed a statistically significant improvement in nausea severity at week 4 (p = 0.0099). However, Study 2 (201 patients) did not demonstrate a statistically significant difference between tradipitant and placebo (p = 0.7411). The FDA also discounted evidence from a 600-patient open-label study showing statistically significant improvements from baseline, as well as data from an expanded access program.
The FDA's analysis of Study 1, which included 11 additional patients excluded per protocol, still showed a statistically significant improvement in nausea severity (p = 0.0359), albeit slightly less pronounced. Despite this, the FDA deemed the overall evidence insufficient.
Vanda argues that the FDA is applying an inappropriately high standard of evidence, requiring two statistically significant studies and clinically meaningful results, which Vanda contends is inconsistent with the statutory requirement for "substantial evidence."
Vanda Seeks a Hearing
Vanda has formally accepted the FDA's offer for a hearing, a process mandated by the Federal Food, Drug, and Cosmetic Act (FDCA) but rarely utilized by the agency. Vanda hopes that the FDA will adhere to the statutory timeline, which requires the hearing to commence within 120 days of the Notice of Opportunity for Hearing (NOOH).
"Vanda will continue to insist that the FDA apply proper legal criteria to Vanda's NDA to make its new therapy available to patients," the company stated, emphasizing its commitment to making tradipitant available to patients suffering from gastroparesis.
Gastroparesis: An Unmet Need
Gastroparesis, affecting an estimated 6 million people in the US, is characterized by delayed gastric emptying, leading to symptoms such as nausea, vomiting, bloating, and abdominal pain. Current treatments are often ineffective or poorly tolerated, and no new drugs have been approved for the condition in over 40 years.
Regulatory and Legal Context
In December 2024, the D.C. Circuit Court of Appeals affirmed the FDA's denial of fast-track approval for tradipitant, supporting the agency's discretion in considering the drug's development plan. This decision underscores the ongoing regulatory challenges faced by Vanda in its pursuit of approval for tradipitant.
