tradipitant (VLY-686) / Vanda, Eli Lilly - LARVOL DELTA

Vanda Pharmaceuticals Provides Regulatory Update on Tradipitant for Motion Sickness (The Malaysian Reserve) - "FDA requests, and Vanda agrees to, a brief extension (to December 5, 2025) for the expedited re-review of the partial clinical hold on long-term studies...Separately, FDA recently issued labeling comments, and labeling discussions have formally begun for the New Drug Application of tradipitant for the prevention of vomiting induced by motion (PDUFA target action date remains December 30, 2025)"

FDA event • PDUFA

Motion Delos: An Open Label Safety and Efficacy of Tradipitant in Participants Affected by Motion Sickness (clinicaltrials.gov) - P3 | N=705 | Active, not recruiting | Sponsor: Vanda Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=500 ➔ 705 | Trial completion date: Apr 2025 ➔ Jun 2026 | Trial primary completion date: Apr 2025 ➔ May 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date

Vanda Pharmaceuticals Reports Positive Results for Tradipitant in Preventing GLP-1 Induced Nausea and Vomiting (PRNewswire) - "This study, which pre-treated patients with either tradipitant or placebo before administering a 1 mg injection of Wegovy, a dose that normally takes 9 weeks of titration to reach, succeeded and met its primary endpoint, with only 29.3% of tradipitant-treated participants (17/58) experiencing vomiting compared to 58.6% on placebo (34/58) (p=0.0016), representing a 50% relative reduction. The study also met the key secondary endpoint of the proportion of participants with vomiting and significant nausea at 22.4% in the tradipitant group (13/58) versus 48.3% on placebo (28/58) (p=0.0039)....A Phase III program is anticipated to initiate in the first half of 2026, positioning tradipitant as a key adjunct to improve outcomes in GLP-1 agonist treatments."

P2 data • Obesity

A Study to Measure the Effects of Using Tradipitant on Nausea and Vomiting After GLP-1R Agonist Use (clinicaltrials.gov) - P2 | N=124 | Completed | Sponsor: Vanda Pharmaceuticals | Recruiting ➔ Completed | N=50 ➔ 124

Enrollment change • Trial completion • Genetic Disorders • Obesity

Comparative Efficacy of Pharmacologic Therapies for Gastroparesis: A Systematic Review and Network Meta-Analysis (ACG 2025) - "Interventions included prucalopride, cisapride, revexepride, metoclopramide, relamorelin, TZP-102, aprepitant, tradipitant, cannabidiol (CBD), and domperidone. A total of 21 trials comprising 2,452 patients were included in the study. For symptom improvement, 19 studies that compared 10 treatments contributed to the network. Cisapride (SMD, 1.88; 95% CI –2.71 to –1.06; SUCRA=0.98), relamorelin (SMD, 1.15; 95% CI –2.15 to –0.16; SUCRA=0.86), and aprepitant (SMD: 0.60; 95% CI –0.88 –0.32; SUCRA=0.76) significantly outperformed the placebo."

Retrospective data • Review • Gastrointestinal Disorder

Responder Analysis for the Efficacy of Tradipitant in Idiopathic and Diabetic Gastroparesis (ACG 2025) - "Nausea responders improved average nausea score significantly from baseline after 12 weeks tradipitant (improvement of -1.40 vs 1.67 at baseline, p< 0.0001). A significant improvement was also seen in the percent of nausea free days (an addition of 49.32% of days for tradipitant vs 28.57% at baseline, p< 0.0001). Significant improvement was also seen in other cardinal gastroparesis symptoms including average times vomited in the past 24 hours (improvement of -0.32 vs 0.40 at baseline, p< 0.0001), stomach fullness (improvement of -1.48 vs 2.86 at baseline, p< 0.0001), not being able to finish a normal-sized meal (improvement of -1.45 vs 2.47 at baseline, p< 0.0001), bloating (improvement of -1.36 vs 2.70 at baseline, p< 0.0001), and upper abdominal pain (improvement of -1.25 vs 1.99 at baseline, p< 0.0001). Tradipitant demonstrated statistically significant improvement from baseline in average nausea severity in this 12 week open label study in both..."

Clinical • Gastrointestinal Disorder

Exposure-Response Efficacy Analysis of Tradipitant in Idiopathic and Diabetic Gastroparesis (ACG 2025) - "Patients improved the average nausea score significantly from baseline after 12 weeks tradipitant (improvement of -1.01 vs 2.14 at baseline, p< 0.0001). A significant improvement was also seen in the percent of nausea free days (an addition of 51.76% of days for tradipitant vs. 19.62% at baseline, p< 0.0001)."

Clinical • Gastrointestinal Disorder

INTEGRATED ANALYSIS: TRADIPITANT EFFECTIVE IN THE PREVENTION OF VOMITING IN MOTION SICKNESS DURING SEA TRAVEL (UEGW 2025) - "The pooled analysis further demonstrates tradipitant's efficacy in the prevention of vomiting associated with motion sickness. Tradipitant could be of significant utility for motion sickness affected travelers in both civilian and military settings across air, land, and sea. Motion sickness remains a significant unmet medical need."

Dyspepsia

OPEN LABEL EFFICACY ANALYSIS OF TRADIPITANT IN IDIOPATHIC AND DIABETIC GASTROPARESIS [WITHDRAWN] (UEGW 2025) - "Tradipitant demonstrated statistically significant improvement from baseline in average nausea severity and percentage of nausea-free days in this 12 week open label study in both idiopathic and diabetic gastroparesis subjects. Additionally, a strong exposure response in nausea improvement was observed when comparing subjects with high drug exposure vs low drug exposure."

Clinical • Gastrointestinal Disorder

RESPONDER ANALYSIS FOR THE EFFICACY OF TRADIPITANT IN IDIOPATHIC AND DIABETIC GASTROPARESIS [WITHDRAWN] (UEGW 2025) - "Tradipitant demonstrated statistically significant improvement from baseline in average nausea severity in this 12 week open label study in both idiopathic and diabetic gastroparesis subjects. Notably, nausea responders on tradipitant also significantly improved in all cardinal gastroparesis symptoms including those unrelated directly to nausea such as abdominal pain. These results suggest tradipitant has the potential for comprehensive gastroparesis symptom relief in tradipitant responders."

Clinical • Gastrointestinal Disorder

VP-VLY-686-3301: Evaluating the Safety and Efficacy of Tradipitant vs. Placebo in Idiopathic and Diabetic Gastroparesis (clinicaltrials.gov) - P3 | N=992 | Completed | Sponsor: Vanda Pharmaceuticals | Recruiting ➔ Completed | N=201 ➔ 992

Enrollment change • Trial completion • Gastrointestinal Disorder

OPEN LABEL EFFICACY ANALYSIS OF TRADIPITANT IN IDIOPATHIC AND DIABETIC GASTROPARESIS (DDW 2025) - "Discussion : Tradipitant demonstrated statistically significant improvement from baseline in average nausea severity and percentage of nausea-free days in this 12 week open label study in both idiopathic and diabetic gastroparesis subjects. Additionally, a strong exposure response in nausea improvement was observed when comparing subjects with high drug exposure vs low drug exposure."

Clinical • Gastrointestinal Disorder

Vanda sues FDA over hearing delay as agency points to mass layoffs, other litigation with the biopharma (FierceBiotech) - "Vanda Pharmaceuticals is suing the FDA again, this time alleging the agency is unlawfully delaying a hearing to discuss the rejection of the biotech's stomach disorder drug last year. The FDA has asked the commissioner’s office to set a hearing by mid-September 2025 for Vanda's request, which was prompted by a complete response letter (CRL). In a letter to the biotech last week, the agency cited multiple reasons for the delay—including the company’s numerous ongoing legal cases with the agency, plus the recent mass federal layoffs. Vanda has filed a lawsuit against the federal agency for the 'unlawful delay' that is currently pending in Washington, D.C., courts, a Vanda spokesperson told Fierce. The drug at the heart of the dispute is tradipitant, an investigational NK-1R antagonist that the FDA rejected as a gastroparesis treatment in September 2024."

Corporate lawsuit • Gastrointestinal Disorder

Motion Syros: tradipitant effective in the treatment of motion sickness; a multicenter, randomized, double-blind, placebo-controlled study. (PubMed, Front Neurol) - P3 | "Tradipitant 170 mg and 85 mg have been confirmed to be effective in the prevention of vomiting associated with motion sickness across varied sea conditions. ClinicalTrials.gov, identifier NCT04327661."

Clinical • Journal

A Study to Measure the Effects of Using Tradipitant on Nausea and Vomiting After GLP-1R Agonist Use (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Vanda Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

Tradipitant Effective in the Reduction of Vomiting Associated with Motion Sickness Across Varied Sea Conditions (S3.003). (PubMed, Neurology) - "Dr. Polymeropoulos has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Vanda Pharmaceuticals ."

Clinical • Journal

A Study to Measure the Effects of Using Tradipitant on Nausea and Vomiting After GLP-1R Agonist Use (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Vanda Pharmaceuticals

New P2 trial • Genetic Disorders • Obesity

Vanda Pharmaceuticals Accepts FDA Opportunity for a Hearing on New Drug Application for Tradipitant in Gastroparesis (PRNewswire) - "Vanda Pharmaceuticals Inc...today provides an update on the tradipitant development program...Today, Vanda accepted FDA's offer of an opportunity for a hearing. Under the statute, a hearing must commence within 120 days after receipt of the NOOH. Vanda hopes that, in break from prior practice, the FDA will adhere to this statutorily mandated time frame. Regardless, Vanda will continue to insist that the FDA apply proper legal criteria to Vanda's NDA to make its new therapy available to patients."

FDA event • Gastrointestinal Disorder

Motion Serifos: a Study to Investigate the Efficacy of Tradipitant in Participants Affected by Motion Sickness (clinicaltrials.gov) - P3 | N=316 | Completed | Sponsor: Vanda Pharmaceuticals | Recruiting ➔ Completed

Trial completion

Open Label Efficacy Analysis of Tradipitant in Idiopathic and Diabetic Gastroparesis (ACG 2024) - "Patients improved the average nausea score significantly from baseline after 12 weeks tradipitant (improvement of -1.01 vs 2.14 at baseline, p< 0.0001). A significant improvement was also seen in the percent of nausea free days (an addition of 51.76% of days for tradipitant vs. 19.62% at baseline, p< 0.0001)."

Clinical • Gastrointestinal Disorder

Exposure-Response Analysis of Open Label Tradipitant in Idiopathic and Diabetic Gastroparesis in Study VP-VLY-686-3301 (ACG 2024) - "Patients in the High PK subgroup had statistically improved nausea severity at Week 12 compared to the Low PK subgroup (-1.19 vs. -0.78, respectively; p< 0.0001), including at baseline nausea severity scores of ≥2 (-1.61 vs. -0.98, respectively; p< 0.0001) and ≥2.5 (-1.77 vs."

Clinical • Gastrointestinal Disorder

OPEN LABEL EFFICACY ANALYSIS OF TRADIPITANT IN IDIOPATHIC AND DIABETIC GASTROPARESIS (UEGW 2024) - "Tradipitant demonstrated statistically significant improvement from baseline in average nausea severity and percentage of nausea-free days in this 12 week open label study in both idiopathic and diabetic gastroparesis subjects. Additionally, a strong exposure response in nausea improvement was observed when comparing subjects with high drug exposure vs low drug exposure."

Clinical • Gastrointestinal Disorder

MOTION SERIFOS: TRADIPITANT EFFECTIVE IN THE PREVENTION OF VOMITING IN MOTION SICKNESS DURING SEA TRAVEL (UEGW 2024) - "Tradipitant could be of significant utility for motion sickness affected travelers in both civilian and military settings across air, land, and sea. Given the adverse effects and incomplete efficacy of currently available therapies, there remains a need for a novel efficacious therapeutic with a desirable tolerability profile."

Late-breaking abstract • Pain

EXPOSURE-RESPONSE ANALYSIS OF OPEN LABEL TRADIPITANT IN IDIOPATHIC GASTROPARESIS IN STUDY VP-VLY-686-3301 (UEGW 2024) - "A significant exposure response was seen in idiopathic gastroparesis patients receiving open label tradipitant for 12 weeks. Patients with higher blood levels of tradipitant significantly improved in average nausea severity and in endpoints measuring overall gastroparesis symptoms compared to subjects with low drug blood levels."

Clinical • Gastrointestinal Disorder • Rare Diseases

VP-VLY-686-2301: Study to Assess the Efficacy of VLY-686 in Relieving Symptoms of Gastroparesis (clinicaltrials.gov) - P2 | N=152 | Completed | Sponsor: Vanda Pharmaceuticals | Unknown status ➔ Completed

Trial completion • Gastrointestinal Disorder