Tradipitant - Vanda Pharmaceuticals
Alternative Names: LY-686017; VLY 686Latest Information Update: 06 Dec 2023
At a glance
- Originator Eli Lilly and Company
- Developer Eli Lilly and Company; National Institute on Alcohol Abuse and Alcoholism; Vanda Pharmaceuticals
- Class Anti-inflammatories; Antipruritics; Antivirals; Anxiolytics; Behavioural disorder therapies; Chlorobenzenes; Gastrokinetics; Pyridines; Skin disorder therapies; Small molecules; Triazoles
- Mechanism of Action Neurokinin 1 receptor antagonists; Substance P inhibitors
-
Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
Highest Development Phases
- Preregistration Gastroparesis
- Phase III Atopic dermatitis; COVID 2019 infections; Motion sickness
- Phase II Pruritus
- Discontinued Alcoholism; Social phobia
Most Recent Events
- 04 Dec 2023 Preregistration for Gastroparesis in USA (PO)
- 04 Dec 2023 FDA assigns PDUFA action date of (18/09/2024) for tradipitant for Gastroparesis
- 21 Jun 2023 Pooled efficacy data from the phase III VP-VLY-686-3301 and VP-VLY-686-2301 trials in Gastroparesis presented at the Digestive Disease Week 2023 (DDW-2023)
Development Overview
Introduction
Tradipitant is a small molecule neurokinin 1 (NK1) receptor antagonist, being developed by Vanda Pharmaceuticals for the oral treatment of gastroparesis, pruritus, atopic dermatitis, COVID-2019 infections and motion sickness. Tradipitant blocks substance P from acting on NK1 receptors in the brain. Substance P is released in response to stress and gives rise to anxiety. Blocking the NK1 receptor from Substance P may be useful in treating a variety of conditions, including anxiety, substance dependence, nausea and vomiting, pruritus and heterotopic ossification. Candidate is under review for gastroparesis in the US. Clinical development for atopic dermatitis, COVID-2019 infections, pruritus and motion sickness is underway in the US and Germany.
Tradipitant was undergoing phase II development with Eli Lilly, as LY 686017, for the treatment of alcoholism and social phobia. However, development was discontinued and the rights were transferred to Vanda for further development. Phase I development for pruritus was conducted in Switzerland. However, no recent reports of development were identified.
Company Agreements
In April 2012, Vanda Pharmaceuticals acquired an exclusive worldwide license to develop and commercialise tradipitant for all human indications from Eli Lilly. Under the terms of the agreement, Vanda paid an initial license fee of $US1.0 million and will be responsible to pay for all development costs. Eli Lilly will be eligible for payments based upon achievement of specified development and commercialisation milestones as well as tiered-royalties on net sales. These milestones include $US4.0 million for pre-NDA approval milestones and up to $US95.0 million for future regulatory approval and sales milestones [1] .
Key Development Milestones
Gastroparesis
In December 2023, US FDA accepted the filing of Vanda's New Drug Application (NDA) for tradipitant for the treatment of symptoms of gastroparesis. The FDA has set September 18, 2024 as the target date for its decision under the Prescription Drug User Fee Act (PDUFA). In support of this application, the FDA accepted for review Vanda's non-animal preclinical toxicology data derived from microphysiological systems that was provided by Vanda in the absence of a nine-month toxicity dog study [2] . In August 2022, Vanda held a pre-NDA meeting with the US FDA to discuss the planned New Drug Application (NDA) submission for tradipitant in the short-term treatment of nausea in gastroparesis. In August 2020, Vanda Pharmaceuticals reported completion of additional preclinical efficacy and safety studies to support prospective submission of a New Drug Application (NDA) with the US FDA to treat patients for 12 weeks or less with nausea in gastroparesis. Based on complete data package, the US FDA has communicated to Vanda that it is considering treatment of tradipitant for the short-term relief of nausea in gastroparesis. Also, The US FDA has advised the Vanda to collect safety data from a 9-month non-rodent chronic toxicity study, in order to expand treatment in clinical trials beyond 12 weeks [3] [4] .
In April 2019, Vanada declared that additional chronic toxicity studies demanded by the FDA in order to lift the partial clinical hold were unjustified, and the company has already submitted the required information, in accordance with applicable law and FDA regulations, regarding the safety of tradipitant, to the FDA to support the continued study of tradipitant in patients beyond 12 weeks. The company has announced this, when even after the re-evaluation, the US FDA indicated that partial clinical hold will continue, until the company provides data from chronic toxicity studies in canines, monkeys or minipigs. Followed by a lawsuit filed by Vanda, in February 2019, against the FDA in the United States District Court, for the District of Columbia (DC District Court), challenging the FDA's legal authority to issue the partial clinical hold, and seeking an order to set it aside, the US FDA had filed a motion for voluntary remand to the agency and for a stay of the case. In March 2019 the DC District Court had approved the FDA's request for voluntary remand and returned the matter to the FDA for further consideration. Thus, again in April 2019, Vanda and the FDA filed a Joint Motion for extension of time to propose a scheduling order for this matter, and in response, the DC District Court has granted the motion, thereby extending the deadline until May 2019, for the FDA and Vanda to file proposals regarding a scheduling order [5] [6] .
As of May 2022, Vanda Pharmaceuticals released data from completed pooled analysis of two clinical studies of tradipitant in gastroparesis consisting of 342 patients [7] .
As at August 2020, Vanda Pharmaceuticals had resumed the gastroparesis programme, that was earlier suspended due to the COVID-2019 pandemic [8] .
In February 2022, Vanda Pharmaceuticals released data for the phase III study for the continued treatment of gastroparesis with tradipitant and reported that the trial did not meet its prespecified primary endpoint which was the difference between drug and placebo on the change of the severity of nausea from baseline at week 12 of treatment (VP-VLY-686-3303; NCT04474990) [9] . In July 2020, Vanda Pharmaceuticals reported that the US FDA authorised a single patient in USA, under an Individual Patient Expanded Access protocol for the continued treatment of gastroparesis with tradipitant. The patient had participated in phase III trial [see below]. The patient has been granted an expanded access to the drug for an additional 6 months with the potential to renew upon written request containing additional safety information collected during those 6 months. The company will not collect the safety data from this cohort of expanded access patients and include the data in New Drug Application (NDA) for gastroparesis. Partial clinical hold that US FDA has placed, does not apply to this individual-patient protocol [4] [10] [11] .
In May 2023, efficacy data from combined phase III VP-VLY-686-3301 trial (see below) and phase II VP-VLY-686-2301 trials (see below) were presented at Digestive Disease Week 2023 (DDW-2023) [12] .
In July 2019, Vanda Pharmaceuticals initiated a phase III trial to investigate the safety and efficacy of tradipitant versus placebo in relieving symptoms of gastroparesis (NCT04028492; VP-VLY-686-3301). The randomised, double-blind, placebo-controlled trial intends to enrol approximately 200 patients in the US [13] . Earlier, in May 2019, Vanda Pharmaceuticals conducted a meeting with the US FDA to confirm the pathway for regulatory approval of tradipitant for the treatment of gastroparesis [14] . As at August 2020, 30% of targeted enrolment was completed in the trial. Enrolment in the study is expected to be completed in the first half of 2021 [4] [8] . In May 2021, Vanda Pharmaceuticals announced its intention to complete enrolment of patients in the second quarter of 2021 [15] . In July 2021, Vanda Pharmaceuticals announced that the phase III study of tradipitant in gastroparesis is nearing completion with 95% of the target 200 patients already enrolled [16] . In November 2021, Vanda Pharmaceuticals announced completion of enrollment in phase III study [17] . In February 2022, results from the trial were released by Vanda Pharmaceuticals [18] . In August 2022, efficacy data from the trial were presented at the 30th United European Gastroenterology Week (UEGW-2022) [19] [20] .
Prior to October 2021, Vanda Pharmaceuticals initiated an open label extension of the phase II trial in patients with gastroparesis. The patients who completed the randomized, double blind, placebo controlled phase II trial [see below NCT02970968], were invited to enter the open label extension phase for an additional eight week [21] . In April 2018, Vanda had submitted a protocol amendment to the FDA, proposing a 52-week open-label extension (OLE) period for patients who had completed a phase II study in gastroparesis. On the basis of the feedback from the FDA, in May 2018, Vanda amended the protocol limiting the duration of treatment in the study to a total of three months, while continuing to seek further dialogue with the FDA on extending the study duration to 52-weeks. In September 2018, Vanda submitted a new follow-on 52-week OLE protocol to the FDA (2302) for patients who had completed a phase II study and no patients were enrolled in any study beyond 12 weeks [6] . In October 2021, Vanda Pharmaceuticals released efficacy data from an open label extension of phase II trial at the 29th European Gastroenterology Week (UEGW-2021) [22] .
In July 2020, Vanda Pharmaceuticals completed a phase II trial that evaluated the efficacy and safety of tradipitant in patients with gastroparesis (VP-VLY-686-2301; NCT02970968). The randomised, double blind trial was initiated in November 2016, and enrolled 152 patients in the US. In December 2018, Vanda Pharmaceuticals presented positive efficacy and safety results from the trial and announced that tradipitant met the primary endpoint of nausea, the significant increase in nausea free days, and the reported overall symptom improvement in patients with gastroparesis. Results from the study showed that tradipitant was well tolerated with comparable rates of adverse events between the tradipitant and placebo groups. In October 2019, the company presented the efficacy data at the 27th United European Gastroenterology Week (UEGW-2019) [23] . In May 2020, Vanda Pharmaceuticals presented the clinical data at the Digestive Disease Week 2020 (DDW-2020) [24] [25] [26] [27] [28] .
Atopic Dermatitis
In October 2020, Vanda Pharmaceuticals completed the phase III EPIONE 2 trial that was designed to evaluate the efficacy of tradipitant in patients with atopic dermatitis (VP-VLY-686-3102; NCT04140695). The randomised, double-blind, placebo-controlled trial was initiated in October 2019 and enrolled 87 patients in the US [29] [30] . As at August 2020, recruitment in the atopic dermatitis programme was on hold, due to the COVID-2019 pandemic [8] .
In February 2020, Vanda Pharmaceuticals completed the EPIONE 1 phase III trial that evaluated the efficacy of tradipitant in patients with atopic dermatitis (VP-VLY-686-3101; NCT03568331). The primary outcome of the study was reduction of worst itch in atopic dermatitis measured by Numerical Rating Scale at week 8.The multi-center, randomised, double-blind, placebo-controlled study was initiated in June 2018 and recruited 375 patients in the US [30] [31] . In the same month, the company released efficacy data of tradipitant which failed to meet the primary endpoint of reduction of pruritus in patients with atopic dermatitis [32] . In April 2021, efficacy and safety data from the trial were presented at American Academy of Dermatology Virtual Meeting Experience 2021 (AAD-VMX-2021) [33] .
Alcoholism
Eli Lilly and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) conducted a phase II trial to evaluate tradipitant in 75 patients with alcohol dependence (NCT00310427). Patients were randomised to receive either 50mg of tradipitant or placebo every morning for 28 days. In the last week of the study, patients underwent functional magnetic resonance imaging (fMRI) to evaluate blood flow to brain structures thought to be involved in craving and anxiety. Craving for alcohol was also evaluated using rating scales and the Trier Social Stress Test.
COVID-2019 infections
In August 2021, Vanda Pharmaceuticals announced that enrollment was closed in the ODYSSEY trial because the trial met the pre-defined futility criteria, indicating that it is unlikely to succeed in its pre-specified primary endpoint. Earlier, in April 2020, Vanda Pharmaceuticals initiated the phase III ODYSSEY trial and enrolled first patient to investigate the efficacy and safety of tradipitant 85 mg orally given twice daily to treat inflammatory lung injury associated with severe or critical COVID-2019 infections (NCT04326426; VLY-686-3501). The trial intended to enrol approximately 300 patients aged 18-90 with severe COVID-2019 infection suffering from pneumonia in the US. Earlier, Vanda received the US FDA permission to proceed with the study for the treatment and prevention of pneumonia associated with COVID-2019. In August 2020, Vanda Pharmaceuticals released interim analysis data from the trial [34] [35] [36] [37] [38] .
Motion sickness
In June 2023, Vanda Pharmaceuticals initiated a phase III trial (Motion Serifos) to evaluate the efficacy of tradipitant in the treatment of motion sickness (NCT05903924, VP-VLY-686-3404). The multi-center, randomised, parallel, double-blind, placebo-controlled trial intends to enroll approximately 300 patients in the US (PO) [39] .
In February 2023, Vanda Pharmaceuticals initiated a phase III Motion Delos trial to evaluate the efficacy and safety of tradipitant for the treatment of motion sickness (NCT06138613 ; VP-VLY-686-3403). The open label trial intends to enroll approximately 300 patients in the US
As of August 2021, phase III development of tradipitant in the treatment of motion sickness is underway in the US (Vanda Pharmaceuticals pipeline, August 2021). Earlier, Vanda Pharmaceuticals announced that, plans to initiate a phase III trial of tradipitant for the treatment of motion sickness. The plan for the study was discussed with the FDA in a previously held end of phase II meeting, wherein the FDA deemed the programme design to be sufficient for a potential regulatory submission [8] [40] [41] [42] .
As at August 2020, Vanda Pharmaceuticals has resumed preparations in order to commence the motion sickness programme, that is suspended due to the COVID-2019 pandemic [4] [8] .
In January 2019, Vanda Pharmaceuticals initiated a phase II Motion Sifnos trial to evaluate the efficacy of tradipitant in patients with motion sickness (VP-VLY-686-2401; NCT03772340). This randomised, double-blinded trial intends to enrol approximately 250 patients in the US [43] . In July 2019, positive results from the trial were released by Vanda Pharmaceuticals [42] .
Pruritus
In September 2017, Vanda Pharmaceuticals completed a phase II trial that evaluated the safety and efficacy of tradipitant, in patients with treatment-resistant chronic pruritus associated with atopic dermatitis (Study-2102; VP-VLY-686-2102; NCT02651714). Patients received tradipitant 85 mg or placebo orally twice daily. The randomised, double-blind, placebo-controlled trial was initiated in January 2016, and enrolled 168 patients in the US [44] [45] . In September 2017, Vanda Pharmaceuticals released results for the trial, which demonstrated that tradipitant improved itch, and disease severity in atopic dermatitis patients [46] . In February 2018, the company presented interim results of the study at the 76th Annual Meeting of the American Academy of Dermatology (AAD-2018) [47] .
In September 2017, Vanda intends to meet with the FDA to further define and confirm the clinical development path towards registration of tradipitant in the treatment of patients with atopic dermatitis. The company plans to hold an end of Phase II meeting with the US FDA in the first quarter of 2018 [48] [46] .
The primary endpoint defined as overall effect of the pre-defined dose of tradipitant on itch, as measured by a 100mm visual analogue scale was not met in a phase II trial (VP-VLY686-2101; EudraCT2013-002931-25; NCT02004041). In March 2015, Vanda completed the randomised, double-blind, placebo-controlled, proof-of-concept phase II trial, assessing the efficacy of tradipitant in patients with treatment-resistant pruritus associated with atopic dermatitis. The trial that was initiated in November 2013, enrolled 68 patients in Germany [49] [50] [51] [52] . Top-line results were released in March 2015 [53] .
Vanda initiated a randomised, double-blind, placebo-controlled, crossover phase I trial in August 2013, to investigate the efficacy of tradipitant in preventing or reducing pruritus in healthy male volunteers after intradermal injections with Substance P (VP-VLY686-1101; NCT01919944). The primary endpoints were itch severity scores on the Verbal Rating Scale and Visual Analogue Scale, 20 minutes after challenge. The trial enrolled 12 subjects in Switzerland, and was completed in November 2013 [54] .
In August 2014, Vanda filed an IND application with the US FDA [55] .
Social phobia
Eli Lilly completed a phase II trial in the US to test the efficacy of tradipitant compared with paroxetine in the treatment of social anxiety disorder (NCT00191022). The primary endpoint of the study was superiority, defined as a statistically greater reduction from baseline to week 12 in the Liebowitz Social Anxiety Scale (LSAS) total score. The study was initiated in December 2004.
Phase I trials
In February 2021, Vanda Pharmaceuticals initiated a phase I trial to evaluate the effects of tradipitant on satiation, gastric volume, gastric accomodation and gastric emptying in healthy volunteers (VP-VLY-686-1301; NCT04849559). The randomised, single center, double blind, placebo controlled trial will enrol approximately 24 participants in the US. In May 2022, the pharmacodynamic data from the study was presented at Digestive Disease Week, 2022 (DDW-2022) [56] [57] .
In February 2016, Vanda Pharmaceuticals completed a phase I trial that assessed the effect of multiple doses of tradipitant, on CYP3A4 using midazolam as a substrate in healthy volunteers (VP-VLY-686-1102; NCT02621385). The pharmacokinetics, single-group, open-label trial was initiated in November 2015 and enrolled 24 volunteers in Switzerland and the US [58] .
In August 2020, Vanda Pharmaceutical reported completion of additional preclinical studies comprising efficacy and a 2-year carcinogenicity study in which tradipitant was safe and well tolerated. There were no significant safety signals were observed in these studies that would be both predictive of clinical safety and would preclude all further clinical development. Also, The US FDA has advised the Vanda to collect safety data from a 9-month non-rodent chronic toxicity study, in order to expand treatment in clinical trials beyond 12 weeks. Currently clinical trials protocols are limited for 12 week treatment with tradipitant. However, Vanda is not in agreement with the agency with respect to conducting 9-months non-rodent chronic toxicity study, on ground of animal ethics. Vanda is working with the FDA to resolve this disagreement. The company will use the safety and efficacy data from the completed studies to support prospective New Drug Applications (NDAs) in multiple indications that require 12 weeks or less treatment. Also in additional safety data from the clinical studies, tradipitant was well tolerated in individuals who received daily doses ranging from less than 50 mg/day to over 170 mg/day [4] .
Financing information
In August 2013, Vanda Pharmaceuticals announced the sale of shares of common stock, with net proceeds expected to total approximately $US48.3 million. Vanda intends to use the proceeds for commercial launch activities for tasimelteon [see separate profile], research and development activities and for general corporate purposes [59] .
Patent Information
In December 2022, Vanda Pharmaceuticals announced that Lilly owned the NCE patent as well as patent applications directed to polymorphic forms of, and methods of making tradipitant. This patent protection was sought in the US and in other countries worldwide. These patents and patent applications have been licensed to Vanda Pharmaceuticals. The NCE patent covering tradipitant will expire in April 2023, except in the US, where it expires normally in June 2024, subject to any extension that may be received under the Hatch-Waxman Act. Vanda Pharmaceuticals filed additional patent applications based on discoveries made during recent studies with tradipitant [60]
The patent protection covering new chemical entity patent for tradipitant expires in June 2029 in the US based on an anticipated Hatch-Waxman patent term extension, and April 2023 elsewhere. Lilly owns patent applications for polymorphic forms of, and methods of making tradipitant worldwide (Vanda pharmaceuticals form 10-k, March 2017) [1] .
Drug Properties & Chemical Synopsis
- Route of administration PO
- Formulation Capsule, unspecified
- Class Anti-inflammatories, Antipruritics, Antivirals, Anxiolytics, Behavioural disorder therapies, Chlorobenzenes, Gastrokinetics, Pyridines, Skin disorder therapies, Small molecules, Triazoles
- Target Neurokinin 1 receptor; Substance P
- Mechanism of Action Neurokinin 1 receptor antagonists; Substance P inhibitors
-
WHO ATC code
A03A (Drugs for Functional Bowel Disorders)
A03F-A (Propulsives)
D04A-X (Other antipruritics)
J05 (Antivirals for Systemic Use)
N05B (Anxiolytics)
N07B-B (Drugs used in alcohol dependence)
-
EPhMRA code
A3 (Functional Gastro-Intestinal Disorder Drugs)
A3F (Gastroprokinetics)
D4A (Anti-Pruritics, Including Topical Antihistamines, Anaesthetics, etc)
J5 (Antivirals for Systemic Use)
N5B (Hypnotics/Sedatives)
N7E (Drugs Used In Alcohol Dependence)
- Chemical name 1-[2-[1-[3,5-Bis(trifluoromethyl)benzyl]-5-(4-pyridyl)-1H-1,2,3-triazol-4-yl]pyridin-3-yl]-1-(2-chlorophenyl)-methanone
- Molecular formula C28 H16 Cl F6 N5 O
- SMILES C1C=C(C=CN=1)C1=C(N=NN1CC1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)C1C(=CC=CN=1)C(=O)C1C=CC=CC=1Cl
-
Chemical Structure
- CAS Registry Number 622370-35-8
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
cOVID 2019 infections |
Outcome Measure |
Interleukin-6 (IL-6) |
|
|
COVID-19 pneumonia |
Outcome Measure |
Interleukin-6 (IL-6) |
|
|
pruritus |
Brief Summary |
CYP3A4 |
|
|
pruritus |
Brief Title |
tachykinin, precursor 1 Substance P CYP3A4 |
|
|
pruritus |
Official Title |
tachykinin, precursor 1 Substance P CYP3A4 |
|
|
pruritus |
Outcome Measure |
tachykinin receptor 1 |
|
|
social phobia |
Eligibility Criteria |
Thyroid stimulating hormone beta (TSH) |
|
|
urticaria |
Brief Title |
tachykinin, precursor 1 Substance P |
|
|
urticaria |
Official Title |
tachykinin, precursor 1 Substance P |
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Tradipitant - Vanda Pharmaceuticals | CYP3A4 | Brief Summary, Brief Title, Official Title |
| gamma-glutamyltransferase 2 | Outcome Measure | |
| gamma-glutamyltransferase light chain 3 | Outcome Measure | |
| GGT | Outcome Measure | |
| GGTLC4P | Outcome Measure | |
| GGTLC5P | Outcome Measure | |
| Interleukin-6 (IL-6) | Outcome Measure | |
| Substance P | Brief Title, Official Title | |
| tachykinin receptor 1 | Outcome Measure | |
| tachykinin, precursor 1 | Brief Title, Official Title | |
| TF | Outcome Measure | |
| Thyroid stimulating hormone beta (TSH) | Eligibility Criteria |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Alcoholism | - | - | Discontinued (II) | USA | PO / Capsule | Eli Lilly and Company, National Institute on Alcohol Abuse and Alcoholism | 01 Oct 2009 |
| Atopic dermatitis | - | - | Phase III | USA | PO / Capsule | Vanda Pharmaceuticals | 01 Jun 2018 |
| COVID 2019 infections | pneumonia due to COVID-19 infections | - | Phase III | USA | PO / unspecified | Vanda Pharmaceuticals | 02 Apr 2020 |
| Gastroparesis | - | - | Preregistration | USA | PO / Capsule | Vanda Pharmaceuticals | 04 Dec 2023 |
| Motion sickness | - | In adults, In the elderly | Phase III | USA | PO / Capsule | Vanda Pharmaceuticals | 25 Aug 2021 |
| Pruritus | - | Treatment-experienced | Phase II | Germany, USA | PO / Capsule | Vanda Pharmaceuticals | 01 Jan 2016 |
| Pruritus | - | In volunteers | No development reported (I) | Switzerland | PO / Capsule | Vanda Pharmaceuticals | 04 Nov 2017 |
| Social phobia | - | - | Discontinued (II) | USA | PO / Capsule | Eli Lilly and Company | 01 Oct 2009 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Eli Lilly and Company | Originator | USA |
| Eli Lilly and Company | Owner | USA |
| Vanda Pharmaceuticals | Licensee | World |
| National Institute on Alcohol Abuse and Alcoholism | Collaborator | USA |
Credit Suisse Market Status
| Indication | Region | Company | Phase | Expected Launch Year | Probability of Success% | Patent Expiry Year | Expected Generic Entry | Last Update |
|---|---|---|---|---|---|---|---|---|
| Alcohol Dependence | Wrld (50% US) | - | Development Stopped | - | - | - | - | 05 Nov 2023 |
Scientific Summary
Pharmacokinetics
A significant correlation between blood levels of tradipitant and the VAS change from baseline (p < 0.05) was seen during a phase II trial in pruritus. A separate analysis of the time of pruritus assessment revealed that approximately half the patients in the study came in for morning visits for their pruritus assessments and these patients also had higher blood levels of tradipitant than those who came in the afternoon. Patients with a VAS score of greater than 70mm were randomized to receive either 100mg of tradipitant (n = 34) or placebo (n = 35) once a day in the evening, for four weeks in the double-blind trial [62] .
Adverse Events
In phase III EPIONE trial, during 8 weeks of treatment, tradipitant was well-tolerated by all participants and although worst itch was not improved over placebo in the overall study population. There was a large and rapid antipruritic effect in the subset of patients with mild AD [33] [31] .
Results of phase III study for the continued treatment of gastroparesis demonstrated that tradipitant was safe and well-tolerated. Patients treated with tradipitant experienced a similar number of treatment emergent adverse events as patients receiving placebo. The most common adverse event for tradipitant group was diarrhoea, with the frequency higher than placebo group [9] [11] .
In a phase II trial, tradipitant was safe and well tolerated with minimal adverse events recorded. The 8-week, randomised 1:1, double-blind trial is designed to investigate the safety and efficacy of tradipitant 85mg bid in 168 patients with treatment-resistant pruritus associated with atopic dermatitis [46] [45] .
Tradipitant 100 mg was safe and well-tolerated and indicated an adverse event profile that was mild and similar to placebo. Patients with a VAS score of greater than 70mm were randomized to receive either 100mg of tradipitant (n = 34) or placebo (n = 35) once a day in the evening, for four weeks in the double-blind trial [62] .
In VLY-686-2301 study, treatment with tradipitant was well tolerable in patients with gastroparesis. Improvements in core gastroparesis symptoms were observed including nausea, vomiting, bloating, and fullness after meals consistent with an overall improvement. No worsening of any of the core symptoms were observed. Results were reported from a randomised placebo-controlled phase II study [25] [28] .
In clinical studies, tradipitant was well tolerated in individuals who received daily doses ranging from less than 50 mg/day to over 170 mg/day [4] .
Preclinical studies
In preclinical toxicity studies, including a 2-year carcinogenicity study, tradipitant was safe and well tolerated. There were no significant safety signals were observed in these studies that would be both predictive of clinical safety and would preclude all further clinical development [4] .
Pharmacodynamics
As per the results of a phase I study in healthy volunteers, there were no significant effects of tradipitant (85mg) administered for 9 days compared to placebo on gastric emptying (GE), gastric volume, satiation, or symptoms 30 minutes after maximum tolerated volume suggesting that tradipitant does not significantly affect gastric motor functions and GE retardation [56] .
Therapeutic Trials
Updated results of the randomised, double-blind, phase II trial of tradipitant demonstrated a clinically meaningful and statistically significant improvement in measures of itch, disease severity and quality of life in 168 patients with with chronic pruritus associated with atopic dermatitis, refractory to treatment with antihistamines or corticosteroids. Patients receiving tradipitant observed improvment in the Worst Itch VAS scale, when compared with placebo (-44.2 versus -30.6, p = 0.019), the total SCORAD index (-21.3 versus -13.6, p = 0.008), objective SCORAD (-13.3 versus -7.2, p=0.005), the Clinician Global Impression of Change (CGI-C) scale (2.6 versus 3.3, p = 0.007), the Patient Global Impression of Change (PGI-C) scales for itch (2.6 versus 3.2, p = 0.025), Patient Global Impression of Change (PGI-C) scales for disease (2.7 versus 3.5, p = 0.007) and the Patient Benefit Index (PBI) scale (1.7 versus 1.2, p = 0.038). Improvements favouring tradipitant were also observed for Average Itch VAS, subjective SCORAD, and SKINDEX 16, but the differences did not reach significance for these measures [47] . Interim results demonstrated that tradipitant treatment caused significant and clinically meaningful improvement in the intensity of the worst itch patients experienced, and atopic dermatitis disease severity. Tradipitant also exhibited significant effects in a responder analysis for Worst Itch in patients who achieved improvements of ≥ 40 points improvement from baseline in Worst Itch VAS scores (p = 0.037) or ≥ 30 points (p = 0.049). On the pre-specified primary endpoint of Average Itch VAS, tradipitant demonstrated improvement over placebo, which was not significant due to high placebo effect and the lack of sensitivity of this measure. Consistent with the observed improvements in Worst Itch, which is associated with scratching behaviour, tradipitant also showed disease modifying properties by showing significant improvement in the total SCORAD scale (p = 0.008) and objective SCORAD scale (p = 0.005). Tradipitant showed significant improvements in several clinical features of severity of atopic dermatitis, including excoriation, erythema, oozing and dryness. In sub-population of 23 patients who had filaggrin (FLG) loss-of-function (LOF) variant mutation, 3/9 (33%) patients treated with tradipitant responded to the treatment (p = 0.047) [63] [46] [45] .
In phase-III VP-VLY-686-3301 trial, tradipitant showed significant and similar reductions when compared with placebo from baseline at 1.55 and 1.49, respectively. Comparison between treatment arms did not reach statistical significance in this measure. However, in the patient global impression of change (PGI-C) scale, more tradipitant treated patients demonstrated response when compared with placebo both at week 2 (74% v. 58%, p=0.019) and at week 12 (78% v. 66%, p=0.065). Similarly, in the overall patient benefit (OPB) scale, more tradipitant treated patients demonstrated response as compared to placebo both at week 2 (81% v. 62%, p=0.0003) and week 12 (86% v. 71%, p=0.011). Results from a patient responder analysis of PGI-C and OPB score in the Baseline Severity Inflation subgroup showed improvements in nausea, PGI-C, and OPB score at week 2 and week 12 in a larger proportion of patients treated with tradipitant. In the PGI-C scale more tradipitant treated patients demonstrated improvement as compared with placebo at week 2 (86% vs. 53%, p=.002) and at week 12 (84% vs. 65%, p=0.056). For the OPB scale, more tradipitant treated patients demonstrated benefit compared with placebo at week 2 (95% vs. 68%, p=.003) and week 12 (92% vs. 68%, p=.009) [19] [20] [13]
In VLY-686-2301 study, treatment with tradipitant in patients with gastroparesis showed significant improvements in the primary endpoint of change of nausea score as measured by patient daily diaries (-1.2 for tradipitant versus -0.7 for placebo, p = 0.0099). The drug also met the endpoint (p = 0.0160) of improvement in the number of nausea free days. Improvement in the number of nausea free days was 28.8% in tradipitant group while 15.0% in placebo group. Patients receiving tradipitant had a significant decrease in their average nausea score compared with placebo with LS mean difference (95% CI) of -0.53 (-0.92, -0.13, p=0.0099). A clinically meaningful response of 1-point or more improvement on the GCSI total score was observed in 46.0% of patients on tradipitant compared with 24.2% of patients on placebo. Tradipitant also showed significant improvement in scales reflecting overall gastroparesis symptoms including the Gastroparesis Symptom Index (GCSI) (p = 0.0223); Patients Assessment of Upper Gastrointestinal Disorders–Symptoms (PAGI-SYM) (p = 0.0497); and Patient Global Impression of Change (PGI-C) (p = 0.0429) as well as a Clinician Global Impression of Severity (CGI-S) (p = 0.0207). In a subgroup analysis of patients that experienced both nausea and vomiting at baseline (n = 101), tradipitant showed highly significant effects on the primary endpoint of change in nausea score (change of -1.4 for tradipitant versus -0.4 for placebo, p = 0.00002) as well as the number of nausea free days (an addition of 32.3% for tradipitant versus 7.6% for placebo, p = 0.0003). At week 4 compared to baseline a significant increase in nausea free days as measured by GCSDD (28.8% increase on tradipitant vs 15.0% on placebo p=0.0160). Results were reported from a randomised placebo-controlled phase II study [24] [25] [28] .
In the phase II Motion Sifnos trial in participants with prior history of motion sickness, significantly fewer patients on tradipitant vomited than those on placebo. In the overall population (n=126), 39.7% of participants experienced vomiting in the placebo arm as compared to 17.5% of tradipitant arm (p = 0.0039). The Motion Sickness Severity Scale (MSSS) Worst score endpoint was favorable to tradipitant, but the difference did not reach statistical significance, 3.75 versus 3.4, (p= 0.293). In an exploratory analysis under the rough sea condition (n=19), 15.8% of tradipitant arm participants experienced vomiting as compared to 72.2% of the placebo treated arm (p = 0.0009). A significant effect was also seen under the rough sea conditions in the MSSS Worst score of 3.19 for tradipitant arm and 4.57 for placebo (p = 0.0235). Under the calm sea condition (n=44), 18.2% of participants experienced vomiting compared to 26.7% of placebo arm. A similar MSSS Worst score was seen between the two groups, 3.32 and 3.40, for placebo and tradipitant respectively (not significant) [42] [43] .
Efficacy data obtained from an open label extension of a phase II trial indicated -1.74 (1.263, P < 0.0001) as the combined mean standard deviation (SD) change in average daily nausea from baseline to week eight. For patients who originally received tradipitant had the mean SD change in average daily nausea from baseline to week eight was reported to be -1.78 (1.116) compared to -1.71 (1.389) in patients who originally received placebo. For patients who were originally treated with tradipitant or placebo, reported a mean SD of nausea free days of 48.13% (36.5%) and 40.24% (41.61%) respectively [22] [21] .
Pooled analysis:
Combined efficacy data from phase II VP-VLY-686-3301 and phase II VP-VLY-686-2301 trial for tradipitant in patients (n=342) with gastroparesis demonstrated a clinically meaningful and statistically significant improvement in average nausea at week 4 (-1.15 for tradipitant v. -0.85 for placebo, P=0.0138). Significant improvement was seen in the number of nausea free days (20.96% improvement for tradipitant v. 12.52% for placebo, P=0.0085). Tradipitant also showed improvement in other gastroparesis symptoms as measured by the GCSI total score (-0.99 for tradipitant v. -0.76 for placebo, P=0.0265). Responder rates for patient global impression of change (PGI-C) were 79.3% on tradipitant versus 69% on placebo at week 4 (P value = 0.036). For the overall patient benefit, more patients improved on tradipitant versus placebo with 85.3% v. 71.2% at week 4 (P= 0.002). Sensitivity analysis adjusting for drug compliance confirmed the PK population (tradipitant blood levels ≥ 140ng/mL) in the pooled data set (n=284). In the pooled PK Population, tradipitant significantly improved average nausea at week 4 with -1.38 for tradipitant v. -0.85 for placebo (P=0.0001) [12] .
Pooled analysis
In pooled analysis data from two clinical studies in gastroparesis consisting of 342 patients, tradipitant was to found to be superior to placebo in key clinical parameters. In week 4, in intent to treat population, improvement in DD-Nausea (primary endpoint parameter), percent nausea free days, patient global impression scale change (PGI-C), overall benefit score and gastroparesis cardinal symptom index (GCSI) score with tradipitant (n = 175) against placebo (n = 167) was -1.15 vs -0.85, 20.96 vs12.52, 2.72 vs 3.00, 1.13 vs 0.88 and -0.99 vs -0.76, respectively [7] .
Results of the phase III study for the continued treatment of gastroparesis with tradipitant did not meet its prespecified primary endpoint which was the difference between drug and placebo on the change of the severity of nausea from baseline at week 12 of treatment. Both treatment arms showed significant improvements from baseline on nausea as well as the other core symptoms of gastroparesis. Strong evidence of a drug effect across several symptoms and across the duration of study, including a significant and meaningful effect at the prespecified primary endpoint of nausea change at week 12, was noted [9] [11] .
Results from the phase III trial in gastroparesis demonstrated that the trial did not meet its prespecified primary endpoint, but significant treatment effects were observed when adjusting for confounding factors [18] [13] .
Tradipitant did not meet the primary endpoint of overall effect on itch, as measured by a 100mm visual analogue scale due to a large placebo effect, during a phase II trial in pruritus. Improvement from baseline for tradipitant was 40.5nm, compared with 36.5nm seen in the placebo arm (p < 0.0001). Analysis of patients who came in for morning visits indicated VAS change was -54mm in the tradipitant arm, compared with -30.3 in the placebo arm (p < 0.01) and VRS change was -1.46, compared with -0.67 (p < 0.05). CGC-C and PBI values were 2.46 and 1.47, relative to 3.61 and 0.73, respectively (p < 0.05). SCORAD subjective analysis in the tradipitant and placebo arms were -9.58 and -4.36, respectively (p < 0.01). Patients with a VAS score of greater than 70mm were randomized to receive either 100mg of tradipitant (n = 34) or placebo (n = 35) once a day in the evening, for four weeks in the double-blind trial [62] .
In the phase III EPIONE 1 trial, tradipitant did not meet its primary endpoint of mean improvement in WI-NRS (baseline to week 8) (P = 0.567). However, robust antipruritic effect was observed in mild AD patients (rated 1 or 2 at baseline by the validated Investigator Global Assessment for Atopic Dermatitis, P = 0.015). This result was confirmed by daily diary (P = 0.001) and observed after one full day of treatment (P = 0.0457). The trial enrolled 375 patients with atopic dermatitis [33] . In the phase III EPIONE 1 trial, treatment with tradipitant demonstrated improvement in pruritus as measured by the Worst Itch Numeric Rating Scale (WI-NRS), in patients with atopic dermatitis. The magnitude of improvement were reported to be greater with tradipitant than placebo. A significant interaction was reported between baseline disease severity (IGA 1-4) and treatment (p=0.0004). A significantly larger improvement in WI-NRS was reported with tradipitant at the pre-specified endpoint of Week 8 in the full trial population (p=0.0217). Similar effects were reported throughout the treatment periods at all post-randomisation visits comprising weeks 2, 4, 6 and 8. Also a subgroup analysis reported that patients with mild disease severity (23% of study patients, IGA 1, 2) reported the largest improvement over placebo. A 72.5% of tradipitant patients reported clinically meaningful response as compared to 33.3% of placebo patients, as per categorical WI-NRS responder analysis (>4 point improvement [32] [31] .
In interim data from the phase III ODYSSEY trial, 14 day treatment with tradipitant demonstrated statistically significant treatment accelerated clinical improvement by day 7 (HR = 2.55, p = 0.0375) in 60 patients with inflammatory lung injury associated with severe or critical COVID-2019 infections. The benefit was generally consistent among patients of varying degree of severity at baseline. Tradipitant showed numerically improved median time to clinical improvement by day 28 (HR = 1.55, p = 0.2254) when compared with placebo, with median time to improvement 10 days for tradipitant and 28 days for placebo. Overall rates of improvement were similar for both treatment arm and placebo arm and was observed in 57% of patients treated with tradipitant and 50% for placebo.The mortality rate was also similar between the treatment groups with 14.2% for tradipitant and 16.6% for placebo [35] [38]
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 18 Sep 2024 | Regulatory Status | FDA assigns PDUFA action date of (18/09/2024) for tradipitant for Gastroparesis [2] | 06 Dec 2023 |
| 30 Jun 2023 | Regulatory Status | Vanda Pharmaceuticals plans to file a NDA for Gastroparesis in USA in the first half of 2023 [61] | 07 Nov 2022 |
| 31 Dec 2022 | Trial Update | Vanda Pharmaceuticals plans a phase II trial for Functional dyspepsia (In adults, In the elderly) in USA (PO, Capsule) in December 2022 (NCT05653310) (700359637) | 08 Jan 2023 |
| 31 Dec 2021 | Regulatory Status | Vanda Pharmaceuticals plans to launch tradipitant for Gastroparesis in USA, in the second half of 2021 [4] | 04 Sep 2020 |
| 31 Dec 2020 | Regulatory Status | Vanda Pharmaceuticals announces intention to file an NDA with the US FDA for Motion sickness in 2020 [42] | 28 Feb 2020 |
| 31 Mar 2020 | Trial Update | Vanda plans a second phase III trial for Atopic dermatitis in the first quarter of 2020 [6] | 15 Feb 2019 |
| 31 Dec 2019 | Trial Update | Vanda Pharmaceuticals plans a phase III trial in Motion Sickness [14] | 25 Aug 2021 |
| 30 Jun 2019 | Regulatory Status | Vanda plans a meeting with the US FDA to define and confirm the approval path of Tradipitant for Gastroparesis in the second quarter of 2019 [6] | 02 Aug 2019 |
| 30 Jun 2019 | Trial Update | Vanda plans a phase III trial for Gastroparesis in the second quarter of 2019 [6] | 02 Aug 2019 |
| 30 Jun 2018 | Trial Update | Vanda Pharmaceuticals plans a phase III trial for Atopic dermatitis in USA in the first half of 2018 [48] | 04 Jul 2018 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 04 Dec 2023 | Phase Change - Preregistration | Preregistration for Gastroparesis in USA (PO) [2] Updated 06 Dec 2023 |
| 04 Dec 2023 | Regulatory Status | FDA assigns PDUFA action date of (18/09/2024) for tradipitant for Gastroparesis [2] Updated 06 Dec 2023 |
| 05 Nov 2023 | Financial Update | Credit Suisse financial data update Updated 05 Nov 2023 |
| 21 Jun 2023 | Scientific Update | Pooled efficacy data from the phase III VP-VLY-686-3301 and VP-VLY-686-2301 trials in Gastroparesis presented at the Digestive Disease Week 2023 (DDW-2023) [12] Updated 29 Jun 2023 |
| 05 Jun 2023 | Trial Update | Phase-III clinical trials in Motion sickness in USA (PO) (NCT05903924) Updated 20 Jun 2023 |
| 27 Feb 2023 | Trial Update | Vanda Pharmaceuticals initiates enrolment in a phase III Motion Delos trial in Motion sickness in USA (PO, Capsule) (NCT06138613) Updated 22 Nov 2023 |
| 31 Dec 2022 | Patent Information | Vanda Pharmaceuticals files patent applications for tradipitant [60] Updated 14 Mar 2023 |
| 31 Dec 2022 | Patent Information | Vanda Pharmaceuticals in-licenses patent and patent applications for tradipitant from Eli Lily in the US and in other countries worldwide [60] Updated 14 Mar 2023 |
| 16 Dec 2022 | Trial Update | Vanda Pharmaceuticals plans a phase II trial for Functional dyspepsia (In adults, In the elderly) in USA (PO, Capsule) in December 2022 (NCT05653310) Updated 08 Jan 2023 |
| 02 Nov 2022 | Regulatory Status | Vanda Pharmaceuticals plans to file a NDA for Gastroparesis in USA in the first half of 2023 [61] Updated 07 Nov 2022 |
| 10 Aug 2022 | Scientific Update | Efficacy data from a phase-III Vp-Vly-686-3301 trial in Gastroparesis presented at the 30th United European Gastroenterology Week (UEGW-2022) [20] [19] Updated 24 Nov 2022 |
| 03 Aug 2022 | Regulatory Status | Vanda holds a pre-NDA meeting with the US FDA to discuss the planned NDA submission for tradipitant in Gastroparesis [3] Updated 08 Aug 2022 |
| 21 May 2022 | Scientific Update | Pharmacodynamics data from a phase I trial in healthy volunteers presented at the Digestive Disease Week, 2022 (DDW-2022) [56] Updated 18 Jul 2022 |
| 05 May 2022 | Scientific Update | Pooled data efficacy data from a clinical trials in Gastroparesis released by Vanada Pharmaceuticals [7] Updated 11 May 2022 |
| 23 Feb 2022 | Scientific Update | Efficacy data from a phase III trial in Gastroparesis released by Vanda Pharmaceuticals [18] Updated 25 Feb 2022 |
| 04 Feb 2022 | Scientific Update | Efficacy and safety data from a phase III trial in Gastroparesis released by Vanda Pharmaceuticals [9] Updated 08 Feb 2022 |
| 03 Oct 2021 | Scientific Update | Efficacy data from a phase II trial in Gastroparesis presented at the 29th United European Gastroenterology Week (UEGW-2021) [22] Updated 22 Dec 2021 |
| 03 Oct 2021 | Trial Update | Vanda Pharmaceuticals initiates an open label extension of a phase II trial in Gastroparesis in USA (PO), prior to October 2021 Updated 22 Dec 2021 |
| 25 Aug 2021 | Phase Change - III | Phase-III clinical trials in Motion sickness (In the elderly, In adults) in USA (PO) (Vanda Pharmaceuticals pipeline, August 2021) Updated 25 Aug 2021 |
| 03 Aug 2021 | Trial Update | Vanda Pharmaceuticals closes enrolment in its phase III ODYSSEY trial for pneumonia in COVID-2019 infections in USA because the trial met the pre-defined futility criteria [34] Updated 06 Aug 2021 |
| 23 Apr 2021 | Scientific Update | Efficacy and safety data from phase III EPIONE trial in Atopic dermatitis presented at American Academy of Dermatology Virtual Meeting Experience 2021 (AAD-VMX-2021) [33] Updated 27 Jun 2021 |
| 01 Feb 2021 | Trial Update | Vanda Pharmaceuticals initiates a phase I trial in volunteers in USA (PO, Capsules) (NCT04849559) Updated 26 Apr 2021 |
| 14 Oct 2020 | Trial Update | Vanda Pharmaceuticals completes a phase III trial in a phase III EPIONE 2 trial for Atopic dermatitis in USA (NCT04140695) Updated 20 May 2022 |
| 31 Aug 2020 | Regulatory Status | Vanda Pharmaceuticals plans to launch tradipitant for Gastroparesis in USA, in the second half of 2021 [4] Updated 04 Sep 2020 |
| 31 Aug 2020 | Scientific Update | Adverse events data from preclinical trials released by Vanda Pharmaceuticals [4] Updated 04 Sep 2020 |
| 31 Aug 2020 | Scientific Update | Adverse events data from clinical trials released by Vanda Pharmaceuticals [4] Updated 04 Sep 2020 |
| 18 Aug 2020 | Scientific Update | Interim efficacy data from the phase III ODYSSEY trial in COVID-2019 infections released by Vanda Pharmaceuticals [35] Updated 24 Aug 2020 |
| 18 Aug 2020 | Trial Update | Vanda Pharmaceuticals plans clinical trials in Influenza virus infections (with pneumonia) [35] Updated 24 Aug 2020 |
| 05 Aug 2020 | Trial Update | Vanda Pharmaceuticals withholds enrolment in a phase III EPIONE 2 trial for Atopic dermatitis in USA, due to the COVID-2019 pandemic [8] (NCT04140695) Updated 13 Sep 2020 |
| 05 Aug 2020 | Trial Update | Vanda Pharmaceuticals resumes the Gastroparesis and Motion sickness programmes [8] Updated 10 Aug 2020 |
| 05 Aug 2020 | Trial Update | Vanda Pharmaceuticals temporarily suspends enrolment in the Atopic dermatitis programme, due to the COVID-2019 pandemic, prior to August 2020 [8] Updated 10 Aug 2020 |
| 18 Jul 2020 | Trial Update | Vanda Pharmaceuticals completes a phase II trial in Gastroparesis in USA (PO) (NCT02970968) Updated 05 Aug 2020 |
| 15 Jul 2020 | Trial Update | Vanda Pharmaceuticals initiates an expanded-access programme for Gastroparesis in USA [10] (NCT04474990) Updated 15 Jul 2020 |
| 22 May 2020 | Scientific Update | Efficacy data from a phase II trial in Motion sickness presented at the Digestive Disease Week 2020 (DDW-2020) [24] Updated 31 Jul 2020 |
| 20 Apr 2020 | Biomarker Update | Biomarkers information updated Updated 02 Oct 2021 |
| 14 Apr 2020 | Trial Update | Vanda Pharmaceuticals initiates enrolment in the phase III ODYSSEY trial for pneumonia in COVID-2019 infections in USA (NCT04326426) [36] Updated 17 Apr 2020 |
| 02 Apr 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections in USA (PO) [37] Updated 08 Apr 2020 |
| 25 Feb 2020 | Scientific Update | Efficacy data from the phase III EPIONE trial in Atopic dermatitis released by Vanda Pharmaceuticals [32] Updated 28 Feb 2020 |
| 01 Feb 2020 | Trial Update | Vanda Pharmaceuticals completes the phase III EPIONE trial in Atopic dermatitis in USA (PO, Capsule) (NCT03568331) Updated 04 May 2020 |
| 21 Oct 2019 | Trial Update | Vanda Pharmaceuticals initiates the phase III EPIONE 2 trial for Atopic dermatitis in USA [30] (NCT04140695) Updated 15 Nov 2019 |
| 19 Oct 2019 | Scientific Update | Efficacy data from a phase II trial in Gastroparesis presented at the 27th United European Gastroenterology Week (UEGW-2019) [23] Updated 26 Feb 2020 |
| 30 Sep 2019 | Trial Update | Vanda Pharmaceuticals completes enrolment in the phase III EPIONE 1 trial for Atopic dermatitis in USA [30] Updated 15 Nov 2019 |
| 31 Jul 2019 | Trial Update | Vanda Pharmaceuticals plans a phase III trial in Motion Sickness [14] Updated 25 Aug 2021 |
| 23 Jul 2019 | Phase Change - III | Phase-III clinical trials in Gastroparesis in USA (PO) (NCT04028492) Updated 29 Jul 2019 |
| 16 Jul 2019 | Regulatory Status | Vanda Pharmaceuticals announces intention to file an NDA with the US FDA for Motion sickness in 2020 [42] Updated 28 Feb 2020 |
| 16 Jul 2019 | Scientific Update | Efficacy data from a phase II Motion Sifnos trial in Motion sickness released by Vanda Pharmaceuticals [42] (NCT03772340) Updated 18 Jul 2019 |
| 30 Apr 2019 | Regulatory Status | Vanda and the US FDA files a Joint Motion for extension of time to propose a scheduling order for partial clinical hold of tradipitant Updated 08 May 2019 |
| 26 Apr 2019 | Regulatory Status | The US FDA continues with the partial clinical hold on clinical studies of tradipitant after re-evaluation Updated 08 May 2019 |
| 13 Feb 2019 | Regulatory Status | Vanda plans a meeting with the US FDA to define and confirm the approval path of Tradipitant for Gastroparesis in the second quarter of 2019 [6] Updated 02 Aug 2019 |
| 13 Feb 2019 | Trial Update | Vanda plans a phase III trial for Gastroparesis in the second quarter of 2019 [6] Updated 02 Aug 2019 |
| 13 Feb 2019 | Regulatory Status | Vanda plans to submit NDA to the US FDA for Gastroparesis [6] Updated 15 Feb 2019 |
| 13 Feb 2019 | Trial Update | Vanda plans a second phase III trial for Atopic dermatitis in the first quarter of 2020 [6] Updated 15 Feb 2019 |
| 05 Feb 2019 | Regulatory Status | Vanda Pharmaceuticals files a complaint against the US FDA for partial clinical hold on clinical studies of tradipitant [5] Updated 07 Feb 2019 |
| 31 Dec 2018 | Phase Change - II | Phase-II clinical trials in Motion sickness (In adults, In the elderly) in USA (PO) (NCT03772340) Updated 19 Dec 2018 |
| 19 Dec 2018 | Regulatory Status | US FDA imposes a partial clinical hold on Vanda Pharmaceuticals studies of tradipitant [5] [6] Updated 07 Feb 2019 |
| 03 Dec 2018 | Scientific Update | Efficacy and adverse events data from a phase II trial in Gastroparesis released by Vanda Pharmaceuticals [25] Updated 07 Dec 2018 |
| 30 Sep 2018 | Trial Update | Vanda Pharmaceuticals completes enrolment in a phase II trial in Gastroparesis in USA [26] Updated 15 Nov 2018 |
| 01 Jun 2018 | Phase Change - III | Phase-III clinical trials in Atopic dermatitis in USA (PO, Capsule) (NCT03568331) Updated 04 Jul 2018 |
| 16 Feb 2018 | Scientific Update | Interim efficacy data from a phase II trial in Pruritus presented at the 76th Annual Meeting of the American Academy of Dermatology (AAD-2018) [47] Updated 08 May 2018 |
| 07 Nov 2017 | Trial Update | Vanda Pharmaceuticals plans a phase III trial for Atopic dermatitis in USA in the first half of 2018 [48] Updated 04 Jul 2018 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Pruritus(In volunteers) in Switzerland (PO, Capsule) Updated 04 Nov 2017 |
| 13 Sep 2017 | Scientific Update | Efficacy and adverse events data from a phase II trial in Pruritus released by Vanda Pharmaceuticals [46] Updated 15 Sep 2017 |
| 01 Sep 2017 | Trial Update | Vanda Pharmaceuticals completes a phase II trial in Pruritus (Treatment-resistant) in USA (PO) (NCT02651714) Updated 14 Nov 2017 |
| 29 Mar 2017 | Patent Information | Eli lilly has patent protection for tradipitant worldwide (Vanda pharmaceuticals form 10-k, March 2017) Updated 07 Apr 2017 |
| 29 Mar 2017 | Patent Information | Eli lilly has patents pending for tradipitant worldwide (Vanda pharmaceuticals form 10-k, March 2017) Updated 07 Apr 2017 |
| 01 Nov 2016 | Phase Change - II | Phase-II clinical trials in Gastroparesis in USA (PO) (NCT02970968) Updated 20 Dec 2016 |
| 27 Jul 2016 | Trial Update | Vanda Pharmaceuticals plans a phase II trial in Gastroparesis [27] Updated 01 Aug 2016 |
| 01 Feb 2016 | Trial Update | Vanda Pharmaceuticals completes a pharmacokinetics phase I trial in Healthy volunteers in Switzerland and USA (PO) (NCT02621385) Updated 04 May 2016 |
| 01 Jan 2016 | Phase Change - II | Phase-II clinical trials in Pruritus (Treatment-resistant) in USA (PO) (NCT02651714) Updated 24 Feb 2016 |
| 01 Dec 2015 | Trial Update | Vanda Pharmaceuticals plans a phase II trial for Pruritus (Treatment resistant) in USA (NCT02651714) Updated 27 Jan 2016 |
| 01 Nov 2015 | Trial Update | Vanda Pharmaceuticals initiates a pharmacokinetics phase I trial in Healthy volunteers in Switzerland and USA (PO) (NCT02621385) Updated 08 Dec 2015 |
| 29 Jul 2015 | Trial Update | Vanda Pharmaceuticals plans a phase II trial for Pruritus (in patients with Atopic dermatitis) [44] Updated 06 Aug 2015 |
| 05 Mar 2015 | Scientific Update | Efficacy, safety and pharmacokinetics data from a phase II trial in pruritus released by Vanda Pharmaceuticals [62] Updated 29 Mar 2015 |
| 04 Mar 2015 | Trial Update | Vanda Pharmaceuticals completes a phase II trial in Pruritis (Treatment resistant) in Germany Updated 10 Mar 2015 |
| 28 Oct 2014 | Regulatory Status | Vanda Pharmaceuticals files an IND application with the US FDA for Puritis [55] Updated 15 Nov 2014 |
| 19 Nov 2013 | Trial Update | Vanda Pharmaceuticals completes a phase I trial in Pruritus in Switzerland (NCT01919944) Updated 26 Nov 2013 |
| 05 Nov 2013 | Phase Change - II | Phase-II clinical trials in Pruritus (treatment-resistant) in Germany (PO) Updated 18 Nov 2013 |
| 05 Nov 2013 | Trial Update | Vanda Pharmaceuticals completes enrolment in its phase I trial for Pruritis in Switzerland (NCT01919944) Updated 11 Nov 2013 |
| 06 Aug 2013 | Phase Change - I | Phase-I clinical trials in Pruritus in Switzerland (PO) Updated 12 Aug 2013 |
| 04 Apr 2013 | Trial Update | Vanda Pharmaceuticals plans a phase II trial for an unspecified indication Updated 30 Apr 2013 |
| 16 Apr 2012 | Licensing Status | Tradipitant licensed to Vanda Pharmaceuticals worldwide [1] Updated 17 Apr 2012 |
| 01 Oct 2009 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Alcoholism in USA (PO) Updated 21 Jan 2010 |
| 01 Oct 2009 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Social phobia in USA (PO) Updated 21 Jan 2010 |
| 31 Mar 2006 | Phase Change - II | Phase-II clinical trials in Alcoholism in USA (PO) Updated 19 Sep 2008 |
| 31 Dec 2004 | Phase Change - II | Phase-II clinical trials in Social phobia in USA (PO) Updated 19 Sep 2008 |
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An Open-Label Extension of a Phase II Clinical Trial assessing efficacy with tradipitant in improving nausea and overall symptoms in patients with gastroparesis
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Carlin JL, Fisher MA, Bagger MS, Madonick DS, Kupersmith CQ, Lascurain ML, et al. Tradipitant, a Novel Neurokinin-1 Receptor Antagonist, Showed Continued Improvement in Nausea and Other Symptoms Associated with Gastroparesis in an Open-Label Extension of a Phase II Clinical Trial. UEGW-2021 2021; abstr. MP111.
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Carlin J, Lieberman V, Dahal A, Keefe M, Xiao C, Birznieks G, et al. Tradipitant, a Novel Nk-1 Receptor Antagonist, Significantly Improved Nausea and Other Symptoms of Gastroparesis in a Phase II Trial. UEGW-2019 2019; abstr. OP137.
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Carlin JL, Lieberman VR, Keefe MS, Xiao C, Birznieks G, Polymeropoulos MH. Tradipitant Treatment Caused Clinically Meaningful and Significant Improvement in Nausea and Other Symptoms of Gastroparesis in a Phase II Study. DDW-2020 2020; abstr. 939.
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Vanda Announces Positive Phase II Study Results for Tradipitant in Patients with Gastroparesis.
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Vanda Pharmaceuticals Reports Third Quarter 2018 Financial Results.
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Vanda Pharmaceuticals Reports Second Quarter 2016 Financial Results.
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Proof of Concept Study to Assess the Efficacy of VLY-686 (Tradipitant) in Relieving Symptoms of Gastroparesis
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A Randomized, Double-blind, Placebo-controlled, Efficacy Study of the Neurokinin-1 Receptor Antagonist VLY-686 in Patients With Atopic Dermatitis
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Vanda Pharmaceuticals Reports Third Quarter 2019 Financial Results.
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A Randomized, Double-Blind, Placebo-Controlled Efficacy Study of The Neurokinin-1 Receptor Antagonist VLY-686 in Patients With Atopic Dermatitis
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Vanda Reports results from the EPIONE study of Tradipitant in the treatment of Pruritus in Atopic Dermatitis.
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Brzezynski JL, Kaden AR, Mohrman MA, Wang J, Smieszek SP, Przychodzen B, et al. Neurokinin-1 receptor antagonist tradipitant improves itch associated with mild atopic dermatitis: Results from EPIONE, a randomized clinical trial. AAD-VMX-2021 2021; abstr. 27595.
Available from: URL: https://eposters.aad.org/abstracts/27595 -
Vanda Pharmaceuticals Closes Enrollment In The ODYSSEY Study Comparing Tradipitant And Placebo In Hospitalized COVID-19 Pneumonia Patients.
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Vanda Pharmaceuticals' Interim Analysis from ODYSSEY Study Shows Tradipitant may Accelerate Clinical Improvement in Patients with COVID-19 Pneumonia.
Media Release -
Vanda Pharmaceuticals, Northwell Health Conduct ODYSSEY Trial In Patients With Severe COVID-19 Pneumonia.
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Vanda Pharmaceuticals Announces the Initiation of ODYSSEY, an FDA Approved Clinical Study of Tradipitant in Hospitalized Patients with Severe COVID-19 Pneumonia.
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ODYSSEY: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Tradipitant in Treating Inflammatory Lung Injury and Improving Clinical Outcomes Associated With Severe or Critical COVID-19 Infection
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Motion Serifos: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Tradipitant in Participants Affected by Motion Sickness During Travel
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Motion Syros: A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Tradipitant in the Treatment of Motion Sickness
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Vanda Pharmaceuticals Reports Fourth Quarter and Full Year 2019 Financial Results.
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Tradipitant Effective in Preventing Motion Sickness.
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Motion Sifnos: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Tradipitant in Subjects Affected by Motion Sickness
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Vanda Pharmaceuticals Reports Second Quarter 2015 Financial Results.
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A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Tradipitant in Treatment-resistant Pruritus Associated With Atopic Dermatitis
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Vanda's Tradipitant Improves Itch and Disease Severity in Patients with Atopic Dermatitis.
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Heitman A, Xiao C, Cho Y, Polymeropoulos C, Birznieks G, Polymeropoulos M. Tradipitant Improves Worst Itch and Disease Severity in Patients with Chronic Pruritus Related to Atopic Dermatitis. AAD-2018 2018; abstr. 7788.
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Vanda Pharmaceuticals Reports Third Quarter 2017 Financial Results.
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Vanda Pharmaceuticals Reports Fourth Quarter 2014 and Full Year 2014 Financial Results.
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Vanda Pharmaceuticals Reports First Quarter 2013 Results.
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Vanda Pharmaceuticals Reports Second Quarter 2014 Results.
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A randomized, double-blind, placebo-controlled, proof of concept, antipruritic study of the neurokinin-1 receptor antagonist VLY-686 in subjects with treatment-resistant pruritus associated with atopic dermatitis.
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Affimed Announces Financial Results for Fourth Quarter and Year End 2014.
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A Randomized, Double-Blind, Placebo-Controlled, Four-Way Crossover Study on Itch Control by VLY-686 Administration in Healthy Volunteers After Intradermal Injections of Substance P
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Vanda Pharmaceuticals Reports Third Quarter 2014 Financial Results.
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Khanna L, Zheng T, Atieh J, Torres M, Busciglio I, Harmsen WS, et al. A Single-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Effects of Tradipitant on Satiation, Gastric Volume, Gastric Accommodation, and Gastric Emptying in Healthy Volunteers. DDW-2022 2022; abstr. Su1426.
Available from: URL: https://eposters.ddw.org/ddw/2022/ddw-2022/354901/lehar.khanna.a.single-center.randomized.double-blind.placebo-controlled.study.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2236%2Aot_id%3D27029%2Amarker%3D1773 -
VP-VLY-686-1301: A Single Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of Tradipitant on Satiation, Gastric Volume, Gastric Accommodation and Gastric Emptying in Healthy Volunteers
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An Open-label, Single-sequence Study to Assess the Effect of Multiple Doses of Tradipitant on Cytochrome P450 3A4 Using Midazolam as a Substrate in Healthy Subjects.
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Vanda Pharmaceuticals Inc. Prices Public Offering of Common Stock.
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Vanda Pharmaceuticals Reports Third Quarter 2022 Financial Results.
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Vanda Pharmaceuticals Announces Tradipitant Phase II Proof of Concept Study Results for Chronic Pruritus in Atopic Dermatitis.
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Smieszek S, Xiao D, Welsh S, Polymeropoulos C, Birznieks G, Polymeropoulos M. Tradipitant Response in Atopic Dermatitis patients with Filaggrin Loss-of-Function variants. AAD-2019 2019; abstr. 10098.
Available from: URL: https://www.aad.org/eposters/view/Abstract.aspx?id=10098
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