A Proof of Concept, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of Tradipitant on Nausea and Vomiting After GLP-1R Agonist Administration in Healthy Overweight Class I or Class II Obese Volunteers

The goal of this study is to measure the effects of using Tradipitant after GLP-1R agonist use on nausea and vomiting in healthy overweight, class I, or class II obese volunteers. The study is placebo-controlled with two treatment arms.

Start Date26 Jan 2025

Sponsor / Collaborator

Vanda Pharmaceuticals, Inc.

NCT06836557

/ RecruitingPhase 3

A Multicenter, Open Label, 3-Month Safety Study with Tradipitant in Patients with Idiopathic or Diabetic Gastroparesis

This is a multicenter, open label, 3-month safety study with tradipitant in patients with idiopathic and diabetic gastroparesis.

Start Date09 Jan 2024

Sponsor / Collaborator

Vanda Pharmaceuticals, Inc.

NCT05903924

/ CompletedPhase 3

Motion Serifos: a Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Tradipitant in Participants Affected by Motion Sickness During Travel

A multi-center, randomized, double-blind, placebo-controlled study to investigate the efficacy of tradipitant in participants affected by motion sickness during travel

Start Date09 Sep 2023

Sponsor / Collaborator

Vanda Pharmaceuticals, Inc.

100 Clinical Results associated with Tradipitant

100 Translational Medicine associated with Tradipitant

100 Patents (Medical) associated with Tradipitant

Literatures (Medical) associated with Tradipitant

01 Dec 2024·Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

The Efficacy of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Phase 3 Randomized Placebo-Controlled Clinical Trial

Article

Author: Polymeropoulos, Mihael H ; Fisher, Michaela ; Moszczynski, Paula ; Polymeropoulos, Christos ; Birznieks, Gunther ; Madonick, Darby ; Kupersmith, Caleigh ; Carlin, Jesse L ; Camilleri, Michael ; Xiao, Changfu ; Lembo, Anthony ; Smieszek, Sandra

BACKGROUND:

Neurokinin receptor 1 antagonists are effective in reducing nausea and vomiting in chemotherapy-induced emesis. We investigated the safety and efficacy of tradipitant, a neurokinin receptor 1 antagonist, in patients with idiopathic and diabetic gastroparesis.

METHODS:

A total of 201 adults with gastroparesis were randomly assigned to oral tradipitant 85 mg (n = 102) or placebo (n = 99) twice daily for 12 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. Blood levels were monitored for an exposure-response analysis. The primary outcome was change from baseline to week 12 in average nausea severity, measured by daily symptom diary.

RESULTS:

The intention-to-treat (ITT) population did not meet the prespecified primary endpoint at week 12 (difference in nausea severity change drug vs placebo; P = .741) or prespecified secondary endpoints. Post hoc analyses were performed to control for drug exposure, rescue medications, and baseline severity inflation. Subjects with high blood levels of tradipitant significantly improved average nausea severity beginning at early time points (weeks 2-4). In post hoc sensitivity analyses, tradipitant treatment demonstrated strengthened effects, with statistically significant improvements in nausea at week 12.

CONCLUSIONS:

Although tradipitant did not reach significance in the ITT population, a pharmacokinetic exposure-response analysis demonstrated significant effects with adequate tradipitant exposure. When accounting for confounding factors such as baseline severity inflation and rescue medication, a statistically significant effect was also observed. These findings suggest that tradipitant has potential as a treatment for the symptom of nausea in gastroparesis. (ClincialTrials.gov, Number: NCT04028492).

11 Jul 2024·JOURNAL OF MEDICINAL CHEMISTRY

Occurrence of “Natural Selection” in Successful Small Molecule Drug Discovery

Article

Author: Zdrazil, Barbara ; Waldmann, Herbert ; Leeson, Paul D. ; Heinzke, A. Lina ; Pahl, Axel ; Leach, Andrew R. ; Young, Robert J.

Published compounds from ChEMBL version 32 are used to seek evidence for the occurrence of "natural selection" in drug discovery. Three measures of natural product (NP) character were applied, to compare time- and target-matched compounds reaching the clinic (clinical compounds in phase 1-3 development and approved drugs) with background compounds (reference compounds). Pseudo-NPs (PNPs), containing NP fragments combined in ways inaccessible by nature, are increasing over time, reaching 67% of clinical compounds first disclosed since 2010. PNPs are 54% more likely to be found in post-2008 clinical versus reference compounds. The majority of target classes show increased clinical compound NP character versus their reference compounds. Only 176 NP fragments appear in >1000 clinical compounds published since 2008, yet these make up on average 63% of the clinical compound's core scaffolds. There is untapped potential awaiting exploitation, by applying nature's building blocks─"natural intelligence"─to drug design.

07 Feb 2024·Journal of the American Chemical Society

¹⁴N to ¹⁵N Isotopic Exchange of Nitrogen Heteroaromatics through Skeletal Editing

Article

Author: Sarpong, Richmond ; Kraus, Samantha L. ; Carpaneto, Filippo ; Bartholomew, G. Logan ; Sigman, Matthew S. ; Bennett, Raffeal ; Karas, Lucas J. ; Yeung, Charles S.

The selective modification of nitrogen heteroaromatics enables the development of new chemical tools and accelerates drug discovery. While methods that focus on expanding or contracting the skeletal structures of heteroaromatics are emerging, methods for the direct exchange of single core atoms remain limited. Here, we present a method for ¹⁴N → ¹⁵N isotopic exchange for several aromatic nitrogen heterocycles. This nitrogen isotope transmutation occurs through activation of the heteroaromatic substrate by triflylation of a nitrogen atom, followed by a ring-opening/ring-closure sequence mediated by ¹⁵N-aspartate to effect the isotopic exchange of the nitrogen atom. Key to the success of this transformation is the formation of an isolable ¹⁵N-succinyl intermediate, which undergoes elimination to give the isotopically labeled heterocycle. These transformations occur under mild conditions in high chemical and isotopic yields.

News (Medical) associated with Tradipitant

13 Feb 2025

·www.prnewswire.com

Vanda Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results

Q4 2024 total revenues of $53.2 million, +17% compared to Q4 2023 Q4 2024 Fanapt® net product sales of $26.6 million, +18% compared to Q4 2023 Full year 2024 total revenues of $198.8 million, +3% compared to full year 2023 Full year 2025 revenue expected to grow to $210 to $250 million Psychiatry portfolio revenue expected to grow to greater than $750 million in 2030 Fanapt® MAA for bipolar I disorder and schizophrenia submitted in Q4 2024 BysantiTM (milsaperidone) NDA for bipolar I disorder and schizophrenia expected to be submitted in Q1 2025 HETLIOZ® MAA for Smith-Magenis syndrome submitted in Q4 2024 Tradipitant NDA for motion sickness submitted in Q4 2024 Imsidolimab BLA in generalized pustular psoriasis expected to be submitted in 2025 WASHINGTON, Feb. 13, 2025 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced financial and operational results for the fourth quarter and full year ended December 31, 2024. "Strong revenue growth for Fanapt is putting us on a significant growth trajectory for 2025 and beyond, supported also by the commercial performance of Hetlioz and Ponvory. The Fanapt long acting injectable program, the NDA for Bysanti for bipolar disorder and schizophrenia along with its development for major depressive disorder have the potential to drive future growth in our psychiatry portfolio for many years to come," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. "Tradipitant's NDA for motion sickness was filed with a potential approval this year, while we are pursuing approval in gastroparesis and the development of tradipitant to improve tolerability of GLP-1 analog Wegovy. Our anti-inflammatory portfolio, anchored by Ponvory, was strengthened with the addition of imsidolimab from Anaptys, an IL-36 receptor inhibitor for the treatment of generalized pustular psoriasis. We plan to file a BLA later this year while we are exploring registration in Europe and Japan as well as the development of this novel drug for other inflammatory disorders with an unopposed action of the IL-36 system. In 2024 we returned to revenue growth driven by the commercial launches in bipolar disorder and multiple sclerosis and advanced our development pipeline with a number of products at or near marketing applications. All this was achieved by the hard work, ingenuity and efficiency of our organization and its wonderful people." Financial Highlights Fourth Quarter of 2024 Total net product sales from Fanapt®, HETLIOZ® and PONVORY® were $53.2 million in the fourth quarter of 2024, a 17% increase compared to $45.3 million in the fourth quarter of 2023 and a 12% increase compared to $47.7 million in the third quarter of 2024. Fanapt® net product sales were $26.6 million in the fourth quarter of 2024, an 18% increase compared to $22.6 million in the fourth quarter of 2023 and an 11% increase compared to $23.9 million in the third quarter of 2024. HETLIOZ® net product sales were $20.0 million in the fourth quarter of 2024, a 5% decrease compared to $21.1 million in the fourth quarter of 2023 and a 12% increase compared to $17.9 million in the third quarter of 2024. PONVORY® net product sales were $6.5 million in the fourth quarter of 2024, an increase of 11% compared to $5.9 million in the third quarter of 2024. The acquisition of PONVORY® from Actelion Pharmaceuticals Ltd. (Janssen), a Johnson & Johnson Company, was completed on December 7, 2023. Net loss was $4.9 million in the fourth quarter of 2024 compared to net loss of $2.4 million in the fourth quarter of 2023 and net loss of $5.3 million in the third quarter of 2024. Cash, cash equivalents and marketable securities (Cash) was $374.6 million as of December 31, 2024, representing a decrease to Cash of $1.6 million compared to September 30, 2024. Full Year 2024 Total net product sales from Fanapt®, HETLIOZ® and PONVORY® were $198.8 million for the full year 2024, a 3% increase compared to $192.6 million for the full year 2023. Fanapt® net product sales were $94.3 million for the full year 2024, a 4% increase compared to $90.9 million for the full year 2023. HETLIOZ® net product sales were $76.7 million for the full year 2024, a 23% decrease compared to $100.2 million for the full year 2023. The decrease relative to the full year 2023 was the result of continued generic competition in the U.S. PONVORY® net product sales were $27.8 million for the full year 2024. The acquisition of PONVORY® from Janssen was completed on December 7, 2023. Net loss was $18.9 million for the full year 2024, compared to net income of $2.5 million for the full year 2023. Cash was $374.6 million as of December 31, 2024, representing a decrease to Cash of $13.6 million compared to December 31, 2023. Key Operational Highlights Fanapt® (iloperidone) Fanapt® was approved in the second quarter of 2024 for the acute treatment of bipolar I disorder. Vanda initiated the commercial launch of Fanapt® in this indication in the third quarter of 2024. In the fourth quarter of 2024, as compared to the fourth quarter of 2023, new patient starts, as reflected by new to brand prescriptions (NBRx),1 increased by over 160% and Fanapt® net product sales increased by 18%. Vanda initiated a Phase III program for the long acting injectable (LAI) formulation of Fanapt® in the fourth quarter of 2024. Vanda plans to initiate a study of the Fanapt® LAI as a once-a-month injectable for the treatment of hypertension to address both treatment resistance and treatment compliance. Vanda submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the fourth quarter of 2024 for Fanapt® for bipolar I disorder and schizophrenia. Bysanti™ (milsaperidone) Vanda expects to submit a New Drug Application (NDA) for Bysanti™ to the U.S. Food and Drug Administration (FDA) for the treatments of acute bipolar I disorder and schizophrenia in the first quarter of 2025. Exclusivity, including pending patent applications, could extend into the 2040s. Vanda initiated a Phase III clinical study for Bysanti™ as a once-daily adjunctive treatment for major depressive disorder (MDD) in the fourth quarter of 2024. Results are expected in 2026. HETLIOZ® (tasimelteon) Vanda has initiated clinical programs for HETLIOZ® in pediatric insomnia and delayed sleep phase disorder (DSPD) and these programs are ongoing. Vanda's MAA for HETLIOZ® and HETLIOZ LQ® for Smith-Magenis Syndrome (SMS) is pending with the EMA. PONVORY® (ponesimod) Vanda initiated the commercial launch of PONVORY® for the treatment of relapsing forms of multiple sclerosis in the third quarter of 2024. Investigational New Drug (IND) applications for PONVORY® in the treatments of psoriasis and ulcerative colitis were accepted by the FDA in the fourth quarter of 2024. Tradipitant The NDA for tradipitant for the treatment of motion sickness was submitted to the FDA in the fourth quarter of 2024. Vanda initiated a clinical trial to study tradipitant in the prevention of vomiting induced by a GLP-1 analog, Wegovy (semaglutide), in the fourth quarter of 2024. Vanda has accepted the opportunity for a hearing with the FDA on the approvability of the NDA for tradipitant for the treatment of symptoms of gastroparesis. Imsidolimab In February 2025, Vanda announced it entered into an exclusive, global license agreement with AnaptysBio, Inc. (Anaptys) for the development and commercialization of imsidolimab (IL-36R antagonist mAb). Vanda expects to initiate and complete the technology transfer activities in 2025 and immediately begin preparing the Biologics License Application (BLA) and MAA for generalized pustular psoriasis (GPP) for the US and EU. The imsidolimab BLA for GPP is expected to be submitted to the FDA in 2025. Early-Stage Program Highlights VQW-765, an alpha-7 nicotinic acetylcholine receptor partial agonist, is currently in clinical development for the treatment of acute performance anxiety in social situations. Vanda expects to initiate a Phase III program in 2025. The IND application for VCA-894A in the treatment of Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S), an inherited peripheral neuropathy for which there is no available treatment, was accepted by the FDA in 2024. Previously in 2023, VCA-894A was granted Orphan Drug Designation for the same indication. The Phase I clinical study for VCA-894A expects to enroll the patient by mid-2025. In December 2024, Vanda announced that the FDA has granted Orphan Drug Designation for VGT-1849A, a selective antisense oligonucleotide (ASO)-based JAK2 inhibitor for the treatment of polycythemia vera (PV), a form of a rare hematologic malignancy that is estimated to affect 1 in 2,000 Americans. Key Regulatory Milestones Tradipitant NDA for motion sickness submitted in Q4 2024. Fanapt® MAA for bipolar I disorder and schizophrenia submitted in Q4 2024. HETLIOZ® MAA in Smith-Magenis syndrome (SMS) submitted in Q4 2024. Bysanti™ NDA for bipolar I disorder and schizophrenia expected to be submitted in Q1 2025. Imsidolimab BLA in generalized pustular psoriasis expected to be submitted in 2025. GAAP Financial Results Net loss was $4.9 million in the fourth quarter of 2024 compared to net loss of $2.4 million in the fourth quarter of 2023. Diluted net loss per share was $0.08 in the fourth quarter of 2024 compared to diluted net loss per share of $0.04 in the fourth quarter of 2023. Net loss was $18.9 million for the full year 2024 compared to net income of $2.5 million for the full year 2023. Diluted net loss per share was $0.33 for the full year 2024 compared to diluted net income per share of $0.04 for the full year 2023. 2025 Financial Guidance and 2030 Revenue Targets Vanda expects to achieve the following financial objectives in 2025: Vanda is providing 2030 revenue targets. For the psychiatry portfolio alone, Vanda is targeting annual revenue in excess of $750 million in 2030, assuming the potential approval of Bysanti™ for the treatments of acute bipolar I disorder and schizophrenia in early 2026, the potential approval of Bysanti™ for the treatment of MDD, and the potential approval of Fanapt® LAI. Vanda is also targeting total annual revenue in excess of $1 billion in 2030. Conference Call Vanda has scheduled a conference call for today, Thursday, February 13, 2025, at 4:30 PM ET. During the call, Vanda's management will discuss the fourth quarter and full year 2024 financial results and other corporate activities. Investors can call 1-800-715-9871 (domestic) or 1-646-307-1963 (international) and use passcode number 2881765. A replay of the call will be available on Thursday, February 13, 2025, beginning at 8:30 PM ET and will be accessible until Thursday, February 20, 2025 at 11:59 PM ET. The replay call-in number is 1-800-770-2030 for domestic callers and 1-609-800-9909 for international callers. The passcode number is 2881765. The conference call will be broadcast simultaneously on Vanda's website, . Investors should click on the Investors tab and are advised to go to the website at least 15 minutes early to register, download, and install any necessary software or presentations. The call will also be archived on Vanda's website for a period of 30 days. References IQVIA Prescription Data About Vanda Pharmaceuticals Inc. Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit and follow us on X @vandapharma. CAUTIONARY NOTE REGARDING FORWARD LOOKING STATEMENTS Various statements in this press release, including, but not limited to, the guidance provided under "2025 Financial Guidance and 2030 Revenue Targets" above and the related implied growth of Vanda's business, and statements regarding Vanda's plans for pursuit of FDA approval of BysantiTM for the treatments of acute bipolar I disorder and schizophrenia and imsidolimab for the treatment of GPP, and the related timelines; Vanda's expectations with respect to the growth opportunities for its psychiatry frachise; Vanda's consideration of foreign regulatory approval for imsidolimab and its potential development for other inflammatory disorders; Vanda's clinical development plans and expected timelines for Fanapt® LAI, BysantiTM for the treatment of MDD, VQW-765 for the treatment of acute performance anxiety in social situations, and VCA-894A for the treatment of CMT2S; the commercial and therapeutic potential for BysantiTM; the potential to extend patent exclusivity for BysantiTM into the 2040s; the anticipated timing of the initiation and completion of technology transfer activities and the preparation of regulatory filings in the US and EU for imsidolimab; and the prevalence of PV are "forward-looking statements" under the securities laws. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Forward-looking statements are based upon current expectations and assumptions that involve risks, changes in circumstances and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others, Vanda's ability to continue to grow its psychiatry portfolio and overall business; the results of Vanda's review of foreign regulatory opportunities for imsidolmab; Vanda's ability to identify additional indications for imsidolimab; Vanda's ability to complete and submit to the FDA the NDA for BysantiTM for the treatments of acute bipolar I disorder and schizophrenia in the first quarter of 2025; Vanda's ability to complete and submit the BLA for imsidolimab for the treatment of GPP in 2025; Vanda's ability to complete the Phase III clinical study for BysantiTM for MDD and receive results in 2026; Vanda's ability to initiate the Phase III program for VQW-765 in 2025; Vanda's ability to enroll the CMT2S patient in the Phase I clinical study for VCA-894A by mid-2025; Vanda's ability to complete the clinical development of, obtain regulatory approval for, and successfully commercialize, BysantiTM for the treatments of acute bipolar I disorder, schizophrenia and MDD; Vanda's ability to satisfy the conditions necessary to extend BysantiTM's patent exclusivity into the 2040s; Vanda's ability to initiate and complete the technology transfer activities and prepare the BLA and MAA for imsidolimab in the specified timeframes; and the accuracy of the estimate regarding the prevalence of PV. Therefore, no assurance can be given that the results or developments anticipated by Vanda will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Forward-looking statements in this press release should be evaluated together with the various risks and uncertainties that affect Vanda's business and market, particularly those identified in the "Cautionary Note Regarding Forward-Looking Statements", "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's most recent Annual Report on Form 10-K, as updated by Vanda's subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the U.S. Securities and Exchange Commission, which are available at . All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this press release is provided only as of the date of this press release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Corporate Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] Jim Golden / Jack Kelleher / Dan Moore Collected Strategies [email protected] Follow us on X @vandapharma SOURCE Vanda Pharmaceuticals Inc. 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License out/inDrug ApprovalNDAPhase 1Phase 3

04 Feb 2025

·www.pharmaceutical-technology.com

Vanda and AnaptysBio link for generalised pustular psoriasis therapy

The trials assessed the efficacy and safety of the therapy in patients with GPP, a severe skin disorder. Credit: Kmpzzz/Shutterstock. Vanda Pharmaceuticals and AnaptysBio have announced an exclusive worldwide licence agreement to develop and commercialise the fully humanised immunoglobulin G4 (IgG4) antibody, imsidolimab, to treat the severe skin disorder generalised pustular psoriasis (GPP). The agreement follows the completion of two Phase III trials, GEMINI-1 and GEMINI-2, which assessed the efficacy and safety of the therapy. Vanda will pay AnaptysBio $10m upfront along with a $5m payment for the current drug supply. Anaptys will receive future regulatory approval and sales milestones amounting to $35m, along with a 10% net sales royalty. With this deal, Vanda secures the rights to develop, manufacture and commercialise imsidolimab globally. Vanda Pharmaceuticals president, CEO and board chairman Mihael Polymeropoulos stated: “We are excited to add imsidolimab to Vanda’s product portfolio for rare orphan disorders, as well as explore the potential of this IL-36 signal regulator in the treatment of additional inflammatory conditions where the IL-36 homeostatic balance is dysregulated.” Guggenheim Securities and Fenwick & West served as financial advisor and legal counsel respectively to AnaptysBio during the transaction. Vanda was advised by Cantor Fitzgerald & Co. Orrick, Herrington & Sutcliffe provided legal counsel. By blocking IL-36R, Imsidolimab corrects the deficiency of the endogenous IL-36 regulator in GPP patients. With the development programme, including the GEMINI-1 and GEMINI-2 Phase III studies, now concluded, Vanda is preparing for technology transfer activities in 2025. The company will begin preparing the marketing authorisation application (MAA) and biologics licence application (BLA) for regulatory submission in the EU and the US. Regulatory and patent exclusivity for imsidolimab is anticipated to extend into the 2030s. In December 2023, the US Food and Drug Administration accepted a new drug application from Vanda for tradipitant, aimed at treating gastroparesis.

License out/inPhase 3Immunotherapy

27 Jan 2025

·www.prnewswire.com

Vanda Pharmaceuticals Accepts FDA Opportunity for a Hearing on New Drug Application for Tradipitant in Gastroparesis

Highlights faulty FDA review WASHINGTON, Jan. 27, 2025 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today provides an update on the tradipitant development program. Gastroparesis is a serious digestive disorder of the stomach. In patients with gastroparesis, food moves too slowly from the stomach to the small intestine, causing a host of gastrointestinal symptoms including nausea, vomiting, bloating, and abdominal pain. There has been no new drug approved by the FDA in more than 40 years and current treatments are often ineffective or not well tolerated. Unfortunately, it is difficult to study drugs for the treatment of gastroparesis, given the subjective variability of symptom severity and reporting, the variability of symptoms over time, and the spontaneous improvement of symptoms over time that contribute to large placebo responses. Drugs that have been tested in recent years have failed to overcome this placebo effect. Vanda began studying tradipitant, a neurokinin 1 receptor antagonist, almost 10 years ago in patients with gastroparesis. To date, more than a thousand people have been treated with tradipitant, many of them for up to 3 months. Additionally, dozens of people are currently treated through an expanded access program, some of them for more than a year. Vanda has conducted two placebo-controlled studies and one open label study to study the efficacy and safety of tradipitant in gastroparesis. Because of the small patient population and uncomfortable symptoms, patient enrollment is a challenge, studies are difficult to conduct, and the overall program has taken almost ten years to complete. In September of 2023 Vanda submitted a New Drug Application (NDA) seeking approval by the FDA. In September of 2024 the FDA rejected the application via a Complete Response Letter, suggesting that substantial evidence of efficacy was not established at this time. Vanda did not agree with this conclusion and requested through the Freedom of Information Act (FOIA) copies of the FDA reviews of the application, which Vanda has recently received. The FDA is required by the federal Food, Drug, and Cosmetic Act (FDCA) to either approve an application in 180 days or give an opportunity for a hearing before the final decision on the application is rendered by the Secretary. The FDA did not follow this legal requirement, delayed the review by 6 months, and instead of an opportunity for a hearing, as mandated by the FDCA, issued a Complete Response Letter. Nor is the FDA following the law now. By statute, once the FDA issues a proposal to refuse the approval of the application, the applicant must respond with whether they would like to have a hearing with the Commissioner. Even if an opportunity for a hearing is extended and accepted by the applicant, the FDA routinely denies the handful of these hearing requests in a summary judgement proceeding that is not outlined in the statute, without any hearing. The FDA has not had a hearing for an NDA for over 30 years. The FDA has now published in the Federal Register conclusions from its review of Vanda's tradipitant application for the treatment of gastroparesis. Below, Vanda explains the FDA's position, which is informed by the Notice of Opportunity for Hearing (NOOH) and the technical reviews that Vanda obtained through FOIA. Vanda focuses on the efficacy arguments. The FDA disagreed that the clinical data submitted demonstrated substantial evidence of efficacy. Vanda submitted two studies, Study 1 and Study 2. In Study 1, (152 patients), tradipitant was shown to significantly improve the severity of nausea at week 4. In Study 2, (201 patients) both tradipitant and placebo showed improvements, but tradipitant, while numerically better, did not show a statistically significant difference from placebo. In Study 1, Vanda's analysis showed changes in severity for nausea at week 4 equal to 1.25 and 0.73 points for tradipitant and placebo, respectively, and this difference was significant (p value = 0.0099). The FDA performed its own analysis that included 11 additional patients who were excluded, pursuant to the study protocol, for having only partial data (11 placebo and 2 on tradipitant) and reported very similar results, with changes in severity for nausea at week 4 equal to 1.20 and 0.79 points for tradipitant and placebo respectively and this difference was significant (p value = 0.0359). In Study 2, Vanda reported changes in severity for nausea at week 12 equal to 1.55 and 1.49 points for tradipitant and placebo, respectively, and this difference was not significant (p value = 0.7411). The FDA performed its own analysis with similar results, with changes in severity for nausea at week 12 equal to 1.52 and 1.51 points for tradipitant and placebo respectively and this difference was not significant (p value = 0.9895). Vanda conducted additional exploratory analyses for Study 2 to adjust for potential confounders such as baseline severity inflation and rescue medication use. These exploratory analyses showed that tradipitant was superior to placebo in reducing severity of nausea. The FDA disagreed with the validity and interpretation of these analyses. The FDA also discounted other persuasive evidence that Vanda provided, including the efficacy evidence from a 600-patient open label study where tradipitant showed statistically significant improvements from baseline. Further, a statistically significant improvement was seen for patients with higher drug levels in their blood as compared to those with lower drug levels in their blood. The FDA also discounted the evidence from patients in the expanded access program, some treated for more than a year, who showed large improvement while on treatment, and often recurrence of symptoms during treatment interruptions due to FDA approval delays. The FDA similarly discounted the pooled analysis of the two studies that showed a significant effect of tradipitant, extending the significance beyond that seen in Study 1, because it said the results were driven by Study 1. The FDA similarly discounted other supportive evidence from other drugs with the same mechanism of action that improve chemotherapy and postoperative nausea and vomiting and discounted evidence from three placebo-controlled studies where tradipitant was shown to be effective in preventing vomiting associated with motion sickness. The FDA agreed that Study 1 showed that tradipitant statistically significantly improved nausea severity as compared to placebo but still called this evidence not persuasive, because in Study 2, the result was equivocal with both treatments showing a large but almost equal effect. For these reasons, the FDA concluded that the overall assessment of the evidence of efficacy did not meet the substantial evidence threshold. Vanda disagrees with this assessment, and believes that the evidence provided meets the statutory standard of substantial evidence. Congress established the efficacy requirement for the approval of new drugs in 1962. Before that, only safety had to be shown. This addition was highly contested at the time and thus the law was written to require "substantial evidence" based on which an expert may conclude that the drug will have the effect it purports to have. Substantial evidence is a relatively low threshold of evidence. In the context of a civil lawsuit, the United States Supreme Court has explained that "[s]ubstantial evidence … means only such relevant evidence as a reasonable mind might accept as adequate to support a conclusion" and is not a "high" standard. Biestek v. Berryhill, 587 U.S. 97, 103 (2019). The FDA agrees that the substantial evidence standard is "rather low", calling it "more than a scintilla" of evidence. See JA1306, Vanda Pharms. Inc. v. FDA, No. 24-1049 (D.C. Cir. 2024) (FDA's Clinical Investigator Course, presented by Dr. Robert Temple, M.D. (2013)). However, the FDA has interpreted the statutory requirement for "adequate and well controlled studies" to mean least two adequate and well controlled studies each one of them producing a significant "less than p=0.05" result. Additionally, the FDA thought that a federal court added another requirement on top of the statute that results also be "clinically meaningful." Warner-Lambert Co. v. Heckler, 787 F.2d 147 (3rd Cir. 1986). None of these requirements is consistent with the statutory language. Congress chose a specific standard of evidence for the efficacy of drugs, not because it would like to see ineffective drugs approved, but because a standard that is too high would erroneously lead to exclusion of otherwise useful and effective drugs. An evidentiary standard must be calibrated to minimize both false positives and false negatives: the substantial evidence standard does this. The FDA has departed from Congress's standard and tipped that balance by adding the two-study requirement, the significance requirement, and the clinically meaningful requirement. Adhering to these requirements means that drugs that have only substantial evidence of efficacy will be rejected, contrary to the statutory text. And such a rejection can be very impactful, especially in a disorder like gastroparesis that has a serious unmet need and where no new drug has been approved in over 40 years. The question for the Commissioner is whether "a reasonable mind" of an expert may, after reviewing the tradipitant program's evidence for efficacy, conclude that the drug will be useful in improving nausea in gastroparesis, even if some other reasonable expert may conclude otherwise. 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. About Vanda Pharmaceuticals Inc. Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit and follow us on Twitter @vandapharma. CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS Various statements in this press release, including, but not limited to statements regarding the timing of a hearing on the tradipitant data, Vanda's intention to require the FDA to apply proper legal criteria to the review of its NDA for tradipitant and the availability of tradipitant to treat patients with gastroparesis, are "forward-looking statements" under the securities laws. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Forward-looking statements are based upon current expectations and assumptions that involve risks, changes in circumstances and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others,the FDA's adherence to the statutorily mandated time frame for commencing a hearing, the FDA's willingness to apply the statutorily prescribed standard of review in evaluating Vanda's NDA and the FDA's ultimate determination as to the approvability of tradipitant for the treatment of gastroparesis. Therefore, no assurance can be given that the results or developments anticipated by Vanda will be realized, or even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Forward-looking statements in this press release should be evaluated together with the various risks and uncertainties that affect Vanda's business and market, particularly those identified in the "Cautionary Note Regarding Forward-Looking Statements", "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's most recent Annual Report on Form 10-K, as updated by Vanda's subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the U.S. Securities and Exchange Commission, which are available at . All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this press release is provided only as of the date of this press release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Corporate Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] Jim Golden / Jack Kelleher / Dan Moore Collected Strategies [email protected] SOURCE Vanda Pharmaceuticals Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

NDAClinical Result

100 Deals associated with Tradipitant

External Link

KEGG	Wiki	ATC	Drug Bank
D11728	Tradipitant	-	DB12580

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Gastroparesis	NDA/BLA	US	Vanda Pharmaceuticals, Inc.	04 Dec 2023
Motion Sickness	NDA/BLA	US	Vanda Pharmaceuticals, Inc.	-
COVID-19	Phase 3	US	Vanda Pharmaceuticals, Inc.	13 Apr 2020
Lung Injury	Phase 3	US	Vanda Pharmaceuticals, Inc.	13 Apr 2020
Diabetic Gastroparesis	Phase 3	US	Vanda Pharmaceuticals, Inc.	20 Aug 2019
Dermatitis, Atopic	Phase 3	US	Vanda Pharmaceuticals, Inc.	09 Jul 2018
Obesity	Phase 2	US	Vanda Pharmaceuticals, Inc.	26 Jan 2025
Pruritus	Phase 2	DE	Vanda Pharmaceuticals, Inc.	10 Dec 2013
Alcoholism	Phase 2	US	Eli Lilly & Co.	01 Mar 2006
Anxiety Disorders	Phase 2	US	Eli Lilly & Co.	01 Mar 2006

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04327661 (Motion Syros, CTgov)	Phase 3	Motion Sickness	366	Tradipitant (Tradipitant High Dose)	ffilknyezk(twfickmxxr) = yccgjnauap ymeadrpitb (euofqnqbcz, rpwtewsmsk - nicvjjbbra) View more	-	11 Dec 2024
				Tradipitant (Tradipitant Low Dose)	ffilknyezk(twfickmxxr) = jarykkjfuk ymeadrpitb (euofqnqbcz, jgtupkfupy - bqywuhowwr) View more
UEGW2024	Not Applicable	Gastroparesis	-	Tradipitant 85 mg twice a day	dldbhrheip(bzdhdtktor) = sjekkyacfb jvjabqkaos (gbrcfsjzvt ) View more	-	13 Oct 2024
VP-VLY-686-3301 (UEGW2024)	Not Applicable	Diabetic Gastroparesis	531	Tradipitant 85mg BID	zfozbkpjog(loftyiiztt) = eiojhzibny axzdrxmycx (fdrgilqfkv ) View more	Positive	13 Oct 2024
NCT02651714 (CTgov)	Phase 2	Pruritus \| Dermatitis, Atopic	168	Tradipitant (Tradipitant)	cjdzumblwu(tdrrfbhndk) = puyretsnvd gvmcljxjjs (kjjinkvuuw, wfgmkmcvxa - hflejocith) View more	-	13 Jun 2024
				Placebo (Placebo)	cjdzumblwu(tdrrfbhndk) = huvqaivsrm gvmcljxjjs (kjjinkvuuw, vusmxqkjnp - biugmojcrs) View more
NCT02004041 (VP-VLY-686-2101, CTgov)	Phase 2	Pruritus \| Dermatitis, Atopic	69	VLY-686 (VLY-686)	fqcaxmqadh(wqtyvnhimy) = geuswyeghg eflpazpocg (dbtfosimno, jbhkvsprtb - plokhnxkba) View more	-	11 Jun 2024
				Placebo (Placebo)	fqcaxmqadh(wqtyvnhimy) = piaipnbwkg eflpazpocg (dbtfosimno, sktrhgyctb - bnrgixtnek) View more
NCT04327661 (Motion Syros, DDW2024) Manual	Phase 3	Motion Sickness	365	Tradipitant 170mg	vcaumvmyju(pavhfcsfya) = vxguwmyoui niojrpaqvt (yzwkhhwzna )	Positive	19 May 2024
				Tradipitant 85mg	vcaumvmyju(pavhfcsfya) = vafikdwznj niojrpaqvt (yzwkhhwzna )
NCT04327661 (Motion Syros, DDW2024)	Phase 3	Motion Sickness	365	Tradipitant 170mg	ijidivpgix(nnsuydhpsd) = gbvrtgshdo eujygatilt (ewzohhhdbz )	Positive	19 May 2024
				Tradipitant 85mg	ijidivpgix(nnsuydhpsd) = ksrtvaopml eujygatilt (ewzohhhdbz )
NEWS Manual	Phase 3	Motion Sickness	316	Tradipitant 170mg	tokzsrakli(yhisppuxuk) = dylpeoaoij fovqegjvxs (byuqktcpvm )	Positive	16 May 2024
				Tradipitant 85mg	tokzsrakli(yhisppuxuk) = ecwrydhutm fovqegjvxs (byuqktcpvm )
NCT04140695 (EPIONE2, CTgov)	Phase 3	Dermatitis, Atopic	87	Tradipitant (Tradipitant)	rguwdpeskx(oiaoyioqby) = ddjzgiczor numqnwkxqj (bpawmnwolk, cgrjvepklz - ljijveswnt) View more	-	14 May 2024
				Placebo (Placebo)	rguwdpeskx(oiaoyioqby) = mcgubhsihl numqnwkxqj (bpawmnwolk, sgdunvfold - gilroclqqu) View more
NCT03568331 (EPIONE, CTgov)	Phase 3	Dermatitis, Atopic	375	Tradipitant (Tradipitant)	tgyadsloqx(vzgficgpgw) = eaqnlcotpk hiytygsywl (lbzxfyliak, vtcanewddt - jypzmpptpj) View more	-	13 May 2024
				Placebo (Placebo)	tgyadsloqx(vzgficgpgw) = hghworyomg hiytygsywl (lbzxfyliak, ugwirmmikw - pkqrrrotzl) View more

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