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 3, 2019, for the FDA and Vanda to file proposals regarding a scheduling order   .
In October 2019, Vanda Pharmaceuticals initiated the phase III EPIONE 2 trial to evaluate the efficacy of tradipitant in patients with atopic dermatitis (VP-VLY-686-3102; NCT04140695). The randomised, double-blind, placebo-controlled trial is enrolling approximately 350 patients in the US   .
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   . 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  .
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.
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 study intends to enrol approximately 300 patients aged 18-90 with severe COVID-2019 infection who are 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 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 250 patients in the US  . 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  .
In December 2018, Vanda Pharmaceuticals presented positive efficacy and safety results from a phase II study 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 (VP-VLY-686-2301; NCT02970968). The randomised study enrolled 141 patients in the US. Results from the study showed that tradipitant was well tolerated with comparable rates of adverse events between the tradipitant and placebo groups     . 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  . In October 2019, the company presented the efficacy data at the 27th United European Gastroenterology Week (UEGW-2019)  .
Prior to February 2020, Vanda Pharmaceuticals initiated a phase III trial in motion sickness (Vanda Pharmaceuticals pipeline, February 2020). The company also announced the intention to complete a phase III trial, with a plan to file a new drug application (NDA) with the US FDA in 2020    .
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  . In July 2019, positive results from the trial were released by Vanda Pharmaceuticals  .
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   . In September 2017, Vanda Pharmaceuticals released results for the trial, which demonstrated that tradipitant improved itch, and disease severity in atopic dermatitis patients  . In February 2018, the company presented interim results of the study at the 76th Annual Meeting of the American Academy of Dermatology (AAD-2018)  .
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   .
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     . Top-line results were released in March 2015  .
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  .
In August 2014, Vanda filed an IND application with the US FDA  .
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 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  .
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  .