The FDA has declined to approve Vanda Pharmaceuticals' New Drug Application (NDA) for tradipitant, intended for the treatment of gastroparesis symptoms. The decision, communicated through a Complete Response Letter (CRL), indicates that the FDA requires additional studies, a move Vanda contests as inconsistent with expert advice and the scientific understanding of gastroparesis. This rejection marks a setback in the effort to address a condition with limited treatment options, impacting patients who suffer from severe nausea, vomiting, and difficulty in completing meals.
Clinical Trial Data and FDA Concerns
Vanda's application for tradipitant included data from two placebo-controlled studies. One phase 2 study (VP-VLY-686-2301) demonstrated statistically significant improvements in overall gastroparesis symptoms, particularly a reduction in nausea (P = .0099) and an increase in nausea-free days (P = .0160). Secondary endpoints, including the Gastroparesis Cardinal Symptom Index (GCSI) (P = .0223) and Patient Assessment of Gastrointestinal Disorders – Symptoms (PAGI-SYM) (P = .0497), also showed significant improvement.
However, the subsequent phase 3 study (VP-VLY-686-3301) did not achieve statistical significance in the primary endpoint of nausea reduction. Although more patients treated with tradipitant showed response on the PGI-C scale at weeks 2 (74% vs 58%; P = .019) and 12 (78% vs 66%; P = .065), the FDA deemed the overall evidence insufficient. Post-hoc analyses suggested potential confounders, such as rescue medication use and poor compliance, may have masked the drug's beneficial effects.
Vanda's Response and Future Plans
Vanda has expressed strong disagreement with the FDA's decision, asserting that the tradipitant application meets the substantial evidence of efficacy standard and presents a favorable benefit-risk profile. The company highlighted that the FDA's action was delayed by more than 185 days, violating the Food Drug and Cosmetic Act (FDCA) requirements. Vanda also noted that repeated requests to convene an expert advisory committee were denied.
Despite the rejection, Vanda remains committed to pursuing marketing authorization for tradipitant and will continue to support its expanded access program for gastroparesis patients. Additionally, the company plans to submit a separate NDA for tradipitant for the prevention of vomiting in motion sickness later this year.
The Unmet Need in Gastroparesis Treatment
Gastroparesis is characterized by delayed gastric emptying, leading to symptoms such as nausea, vomiting, and difficulty finishing meals. It is often associated with diabetes but can also occur in non-diabetic individuals and has recently been linked to GLP-1 inhibitors. The condition significantly impacts patients' daily lives, and there has been a lack of new FDA-approved treatments in over 40 years.
Regulatory Context and Ongoing Concerns
The FDA has imposed a partial clinical hold on tradipitant clinical protocols exceeding 12 weeks due to safety concerns. This hold, along with the CRL, raises questions about the drug's long-term safety and potential for chronic use. Patients currently treated with tradipitant have filed a citizen petition urging the FDA to approve the treatment, underscoring the urgent need for new therapeutic options.
