The US Food and Drug Administration has approved NEREUS (tradipitant), an oral neurokinin-1 receptor antagonist, for the prevention of motion-induced vomiting in adults. The approval represents the first new pharmacologic treatment for motion sickness in more than 40 years.
Efficacy data from two phase 3 real-world provocation studies conducted aboard boats demonstrated substantial reductions in vomiting incidence. In Motion Syros (n = 365), vomiting occurred in 18% to 20% of patients receiving tradipitant versus 44% receiving placebo. In Motion Serifos (n = 316), vomiting rates ranged from 10% to 18% with tradipitant versus 38% with placebo, yielding risk reductions of 50% to 70%. Across the pivotal program, tradipitant consistently demonstrated statistically significant reductions in vomiting and a favorable safety profile consistent with short-term use.
"This approval underscores the strong scientific evidence in the antiemetic effects of NEREUS in motion sickness. For the first time in over 40 years, patients have access to a novel therapy grounded in modern neuropharmacology, offering effective prevention without the limitations of existing options," said Mihael H. Polymeropoulos, MD, President and Chief Executive Officer and Chairman of the Board of Vanda Pharmaceuticals.
Mechanism of Action
Tradipitant acts as a potent and selective neurokinin-1 receptor antagonist, directly targeting the substance P pathway involved in motion-induced nausea and vomiting.
Safety Profile
In placebo-controlled trials, the most commonly reported adverse reactions were somnolence (6% at 85 mg; 12% at 170 mg) and fatigue (6% at 85 mg; 8% at 170 mg). The prescribing information warns that tradipitant may impair mental and physical abilities required for driving or operating machinery. Concomitant use of central nervous system depressants or strong CYP3A4 inhibitors may potentiate this effect.
Strong CYP3A4 inhibitors may increase drug exposure and adverse reaction risk, as tradipitant is a CYP3A4 substrate. Use should be avoided in patients with severe renal impairment (estimated glomerular filtration rate ≤29 mL/min/1.73 m2) or any degree of hepatic impairment (Child-Pugh class A to C), as the drug has not been studied in these populations. Safety and effectiveness have not been established in pediatric patients. No contraindications are listed.
Disease Burden
Approximately 25% to 30% of US adults—an estimated 65 million to 78 million patients—experience motion sickness symptoms during travel by car, plane, or boat. Worldwide, as many as one-third of patients demonstrate high susceptibility. Although most cases are mild, an estimated 5% to 15% of the population experiences severe, recurrent symptoms that can affect quality of life, either through inadequate control with existing therapies or complete avoidance of motion-provoking activities.
Ongoing Development
Vanda continues clinical development of tradipitant for gastroparesis, a chronic disorder characterized by delayed gastric emptying and persistent nausea and vomiting, as well as for preventing nausea and vomiting induced by glucagon-like peptide-1 receptor agonists—a common adverse effect affecting adherence in obesity and diabetes treatment. The company anticipates commercial launch in the coming months.
Source: Vanda Pharmaceuticals Inc.
