Vanda Blames 'Migration To The Mean' As Nereus Vomiting Cut Falls To 27% From 50%
Management says an extreme-vomiter subgroup, 81% in Phase 3 and 83% in Phase 2, shows the drug's effect is reproducible.
Vanda Pharmaceuticals, a drugmaker whose products include the motion-sickness drug Nereus, defended a weaker late-stage result for the drug in GLP-1-induced vomiting on its third-quarter earnings call Wednesday. CEO Mihael Polymeropoulos said the Phase 3 reduction in vomiting was 27%, against 50% in the smaller Phase 2 study, a gap he attributed to variability rather than a loss of effect.
Variability, not a failed drug
An Oppenheimer analyst asked what explains the gap and whether the supplemental application will rest on the primary endpoint or on post hoc data about extreme vomiting. The primary endpoint counted any single vomiting episode in the week after a semaglutide injection, the same measure used in Phase 2.
Polymeropoulos called the shortfall a "very well understood migration to the mean," noting that positive Phase 2 studies often shrink in Phase 3. He said placebo rates were nearly identical in both studies, at 58%, so the difference sat in the drug arm: 29% in Phase 2 versus 42% to 43% in Phase 3.
In patients with more than 10 vomiting episodes in the week after injection, he said, rates were close: 81% in Phase 3 and 83% in Phase 2. "The result remains very robust and reproducible," he said. A post hoc analysis the company published put extreme vomiting at 2.8% on Nereus versus 14.6% on placebo.
The filing plan and the timeline
The declared primary endpoint will anchor the supplemental application, Polymeropoulos said, supported by the Phase 2 study, pooled analyses and a key secondary endpoint, vomiting with severe nausea, which he said also succeeded.
Asked by an H.C. Wainwright analyst about priority review, he said "it's hard to speculate." Without it, he said, review would take about 12 months after filing, pushing any decision beyond late 2027. Vanda plans to meet the FDA first to settle the package.
The Phase 3 study used a single 1 mg semaglutide dose, a strong stimulus chosen to produce many episodes. Polymeropoulos said a pharmacokinetic model suggests similar relative reductions at lower semaglutide exposures.
A launch still small
Vanda develops and sells prescription drugs including Fanapt, HETLIOZ and PONVORY. Nereus reached the US market in the second quarter for motion-sickness prevention, and the GLP-1 use would be a second indication. Nereus net sales were $1.6 million in the third quarter, up 60% from $1 million in the second, and management expects full-year Nereus revenue below $10 million.
Total third-quarter revenue was $69.8 million, up 24% from a year earlier. The net loss was $22.6 million, and cash stood at $140.5 million at September 30.
Vanda's market value was $241 million at the time of the report, and its next dated catalyst is the FDA's December 12 decision date on its Quimilza application.
Sources
- Vanda Pharmaceuticals GAAP EPS of -$0.37 beats by $0.31, revenue of $69.82M beats by $0.7M (NASDAQ:VNDA) | Seeking Alpha — seekingalpha.com
- Vanda: Q3 Earnings Snapshot | 9news.com — Associated Press
- Vanda Pharmaceuticals Targets Major GLP-1 Market Challenge with Positive Trial Outcomes - Vanda Pharmaceu — benzinga.com
- Vanda Pharmaceuticals Announces Positive Results from Study 3601 of NEREUS™ (tradipitant) for Prevention of GLP-1-Induced Vomiting – Company Announcement - FT.com — Financial Times
- Vanda Pharmaceuticals Reports Third Quarter 2026 Financial Results — prnewswire.com
