Last update 01 Jul 2024

Iloperidone

Last update 01 Jul 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone, 4'-(3-(4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidino)propoxy)-3'-methoxyacetophenone, Fanaptum

+ [10]

Target

5-HT2A receptor x D2 receptor

Mechanism

5-HT2A receptor antagonists(Serotonin 2a (5-HT2a) receptor antagonists), D2 receptor antagonists(Dopamine D2 receptor antagonists)

Therapeutic Areas

Other DiseasesNervous System Diseases

Active Indication

Bipolar I disorderManiaSchizophrenia

Inactive Indication

Acute schizophreniaIrritable MoodLiver Diseases+ [5]

Originator Organization

Novartis Pharma AG

Active Organization

Vanda Pharmaceuticals, Inc.

Novartis AG

Probiomed SA de CV

Inactive Organization

Novartis Pharmaceuticals Corp.

Drug Highest PhaseApproved

First Approval Date

US (06 May 2009),

Schizophrenia

Regulation-

Structure

Molecular FormulaC24H27FN2O4

InChIKeyXMXHEBAFVSFQEX-UHFFFAOYSA-N

CAS Registry133454-47-4

Clinical Trials associated with Iloperidone

NCT05648591 / RecruitingPhase 4

Open-label Safety Study of a 1-year 8 to 24 mg/Day Dose Regimen of Iloperidone (FANAPT®) in Adolescent Patients With Schizophrenia or Bipolar I Disorder

To evaluate the safety and tolerability of iloperidone in adolescent patients with schizophrenia or bipolar I disorder for up to 52 weeks of treatment.

Start Date24 May 2023

Sponsor / Collaborator

Vanda Pharmaceuticals, Inc.

NCT05344365 / WithdrawnPhase 2

An Open-label, Sequential Cohorts, Flexible Dose Study to Evaluate the Tolerability, Safety and Pharmacokinetics of Iloperidone in Elderly Patients With Parkinson's Disease Psychosis (PDP)

This is an open-label, sequential cohorts, flexible dose study to evaluate the tolerability, safety and pharmacokinetics of iloperidone in elderly patients with Parkinson's disease psychosis (PDP).

Start Date01 Jun 2022

Sponsor / Collaborator

Vanda Pharmaceuticals, Inc.

NCT04969211 / CompletedPhase 1

An Open-Label, Two-Period, Randomized, Single Oral Dose, Crossover Study to Evaluate the Bioequivalence of VHX-896 Tablets Relative to Iloperidone Tablets in Healthy Volunteers

This is a single center, two-period, randomized study to evaluate the Bioequivalence of VHX-896 Tablets Relative to Iloperidone Tablets in Healthy Volunteers

Start Date30 Jun 2021

Sponsor / Collaborator

Vanda Pharmaceuticals, Inc.

100 Clinical Results associated with Iloperidone

100 Translational Medicine associated with Iloperidone

100 Patents (Medical) associated with Iloperidone

390

Literatures (Medical) associated with Iloperidone

22 Nov 2023·Journal of biomolecular structure & dynamics

In depth molecular interaction analyses of the complex of a proposed CTXM-inhibitor bound to the bacterial enzyme

Article

Author: Shakil, Shazi ; Greig, Nigel H. ; Rizvi, Syed M. Danish

A 'Thumb Rule for Antibiotic Design' against bacteria can be given as, 'The minimum pace of drug design ought to match the swiftness with which bacteria display cutting-edge resistance mechanisms; thereby outwitting the antibiotics and, in turn, the researchers'. Occurrence of drug resistance attributable to CXTM-variants in bacterial pathogens is widespread. In line with our above proposed thumb rule, the present article employed concatenation of virtual screening, docking and simulation to identify a potent in silico validated anti-CTXM-14 ligand. Specifically, this research used the 'MCULE' drug discovery platform to screen a total of 5 million candidate inhibitors to evaluate their binding efficacy with an antibiotic resistance enzyme, CTXM-14 found in bacterial pathogens. A new median approach between 'structure' and 'ligand'-based protocols was employed. Pharmacokinetic profiling was achieved by 'SWISS ADME'. Safety profile for humans was appraised by 'Toxicity Checker'. The complex consisting of the 'Top ligand' (obtained from the screen) harbored within the active pocket of the bacterial CTXM-14 was subjected to 60 ns molecular dynamics simulation with the aid of licensed YASARA STRUCTURE v.21.8.27. Complex tasks were performed by YANACONDA. Fine resolution figures (notably, plots generated from trajectory analyses) were constructed. Simulation snaps were acquired at every 250 picoseconds of the run. The ligand having the IUPAC name as 1-Amino-3-(4-hydroxyphenyl)pyrido[1,2-a]benzimidazole-2,4-dicarbonitrile demonstrated the overall best binding with CTXM-14. Fifteen amino acid residues were found to line the interacting pocket. Remarkably, all of these interacting residues were found to be present among the interacting residues displayed by the reference complex as well, i.e. CTXM-14:Vaborbactam complex (PDB ID 6V7H). A total of 240 simulation snaps were retrieved. The RMSD plot revealed that a plateau was achieved at 32 ns, after which the backbone RMSD fluctuations remained confined within 1.4-2 Å. Video recording of molecular actions was also achieved. In conclusion, this study provides a fresh lead molecule, 1-Amino-3-(4-hydroxyphenyl)pyrido[1,2-a]benzimidazole-2,4-dicarbonitrile against bacterial CTXM-14 protein. The study utilized a new median approach between 'structure' and 'ligand'-based drug design. The lead molecule passed ADMET conditions and an array of medicinal chemistry filters, and is further supported by a stable molecular dynamics. An acceptable skin permeation supports its probable use in antibiotic creams. Moreover, the study provides a clear 'Thumb Rule for Antibiotic Design' against bacteria, which although often assumed, can be clearly stated for the first time. Synthesis of the screening-proposed molecule followed by in-vitro and in-vivo validation is highly recommended.Communicated by Ramaswamy H. Sarma.

01 Oct 2023·Heliyon

New benzisoxazole derivative: A potential corrosion inhibitor for mild steel in 0.5 M hydrochloric acid medium -insights from electrochemical and density functional theory studies

Article

Author: Gaonkar, Santosh L ; G, Anusha ; Sinha, Rajeev K ; Suvarna, Aishwarya S ; Mishma, J N Cheerlin ; P, Preethi Kumari

6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole. HCl (FPBH), a substituted benzisoxazole derivative, was prepared from isonipecotic acid and characterized using various spectroscopic techniques. Using electrochemical examinations such as potentiodynamic polarisation (PDP) and electrochemical impedance spectroscopic (EIS) technique, the corrosion mitigation capabilities of this compound for mild steel (MS) in 0.5 M HCl medium were investigated. Theoretical studies were performed using quantum chemical calculations and density functional theory (DFT). PDP results exhibited the mixed-type behavior of FPBH and showed a maximum efficiency of 94.5 % at 1 × 10^-3 M. The development of a protective adsorbed layer of FPBH decreases the corrosion current density (i_corr) and corrosion rate (CR). The EIS technique revealed that the rise in the charge transfer resistance (R_ct) values and reduction in the thickness of the double-layer capacitance (C_dl) reflected the drop in corrosion rate. The adsorption of FPBH took place through physisorption by conforming Langmuir's isotherm. The DFT method was performed on the optimized structure of FPBH to get additional evidence on the action mode of FPBH with the metal surface.

01 Aug 2023·Molecular psychiatry

Antipsychotic dose, dopamine D2 receptor occupancy and extrapyramidal side-effects: a systematic review and dose-response meta-analysis

Review

Author: Davis, John M ; Wu, Hui ; Takeuchi, Hiroyoshi ; Burschinski, Angelika ; Leucht, Stefan ; Schneider-Thoma, Johannes ; Wang, Dongfang ; Siafis, Spyridon ; Nomura, Nobuyuki

Abstract:

Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D2 receptor (D2R) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3–26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The D2R occupancy curves showed that the risk increased substantially when D2R occupancy exceeded 75–85%, except for D2R partial agonists that had smaller ORs albeit high D2R occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current D2R therapeutic window for EPS.

News (Medical) associated with Iloperidone

08 May 2024

·www.prnewswire.com

Vanda Pharmaceuticals Reports First Quarter 2024 Financial Results

Revenues for Q1 2024 were $47.5 million, an increase of 5% compared to Q4 2023 Cash increase of $5.9 million in Q1 2024 to $394.1 million Fanapt® approved for the acute treatment of bipolar I disorder; commercial launch expected in Q3 2024 Milsaperidone NDA for schizophrenia and bipolar disorder expected to be submitted in early-2025 PONVORY® commercial launch expected in Q3 2024 Tradipitant NDA review for gastroparesis ongoing, PDUFA date of September 18, 2024 Tradipitant second Phase III motion sickness study results expected in Q2 2024; NDA expected to be submitted in Q4 2024 WASHINGTON, May 8, 2024 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced financial and operational results for the first quarter ended March 31, 2024. "We are very proud of our accomplishments in the first quarter of 2024, which were achieved with a small but efficient organization that is enthusiastic to continue developing and commercializing treatments for people who need them," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. "We expect several significant milestones in the coming months, including the launch of Fanapt in acute bipolar I disorder, the launch of Ponvory in multiple sclerosis, the potential approval of tradipitant in gastroparesis, the phase III results of tradipitant in motion sickness, the upcoming NDA filings of milsaperidone in psychiatric disorders and of tradipitant in motion sickness and the initiation of clinical programs in depression, psoriasis, ulcerative colitis and pediatric insomnia. We are confident that our robust revenue, strong cash position and efficient operations position us well for significant growth and value creation in the years to come." Financial Highlights Total net product sales from Fanapt®, HETLIOZ® and PONVORY® were $47.5 million in the first quarter of 2024, a 24% decrease compared to $62.5 million in the first quarter of 2023, and a 5% increase compared to $45.3 million in the fourth quarter of 2023. Fanapt® net product sales were $20.6 million in the first quarter of 2024, a 10% decrease compared to $22.9 million in the first quarter of 2023, and a 9% decrease compared to $22.6 million in the fourth quarter of 2023. HETLIOZ® net product sales were $20.1 million in the first quarter of 2024, a 49% decrease compared to $39.6 million in the first quarter of 2023, and a 5% decrease compared to $21.1 million in the fourth quarter of 2023. The decrease relative to the first quarter of 2023 was the result of continued generic competition in the U.S. PONVORY® net product sales were $6.8 million in the first 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 $4.1 million in the first quarter of 2024, compared to net income of $3.3 million in the first quarter of 2023, and net loss of $2.4 million in the fourth quarter of 2023. Cash, cash equivalents and marketable securities (Cash) was $394.1 million as of March 31, 2024, representing an increase to Cash of $5.9 million compared to December 31, 2023. Key Operational Highlights Psychiatry Portfolio Fanapt® (iloperidone): Vanda announced in April 2024 that the U.S. Food and Drug Administration (FDA) approved Fanapt® as a first line treatment of acute bipolar I disorder in adults. This approval of Fanapt® for acute bipolar I disorder significantly expands the addressable patient population. Patent exclusivity is expected to last at least through late 2027. Vanda is initiating a host of commercial activities, including the expansion of its existing sales force, a prescriber awareness program and a comprehensive marketing program. Milsaperidone: Vanda expects to submit a New Drug Application (NDA) for milsaperidone (also known as VHX-896 and P-88), the active metabolite of Fanapt®, in schizophrenia and acute bipolar I disorder to the FDA in early-2025. If approved, there are pending patent applications that, if issued, could extend exclusivity into the 2040s. Fanapt® LAI: Vanda expects to initiate a Phase III program for the long acting injectable (LAI) formulation of Fanapt® by the end of 2024. Fanapt® LAI could reach the U.S. market after 2026 and there are pending patent applications that, if issued, could extend exclusivity into the 2040s. Vanda is currently planning clinical programs to test the efficacy of Fanapt® and milsaperidone in the treatment of depressive symptoms which, if successful, will significantly expand the addressable patient population. HETLIOZ® (tasimelteon) Vanda is currently planning to initiate a HETLIOZ LQ® program in pediatric insomnia. Although exact estimates of prevalence of insomnia in children are difficult to quantify, it is estimated that 20-40% of children experience significant sleep problems.1,2 There are currently no approved treatments for pediatric insomnia. If ultimately approved for marketing, the addressable patient population for HETLIOZ LQ® would be significantly expanded and market exclusivity would be expected to last into the 2040s. Vanda announced in March 2024 that it received a complete response letter (CRL) from the FDA related to the supplemental New Drug Application (sNDA) for HETLIOZ® in the treatment of insomnia. Vanda is reviewing the CRL and evaluating its next steps. In addition to insomnia, Vanda continues to pursue FDA approval of HETLIOZ® in the treatment of jet lag disorder where the final agency rejection of our application is being challenged in the U.S. Court of Appeals for the D.C. Circuit. Vanda announced in April 2024 that the U.S. Supreme Court denied its petition for a writ of certiorari to review the decision of the U.S. Court of Appeals for the Federal Circuit in Vanda's HETLIOZ® Abbreviated New Drug Application litigation against Teva Pharmaceuticals USA, Inc. (Teva), Apotex Inc. and Apotex Corp (together, Apotex). The lower court decision held that certain claims of Vanda's U.S. Patent Nos. RE46,604; 9,730,910; 10,149,829; and 10,376,487 were invalid. Vanda's suit asserting U.S. Patent No. 11,285,129 will be infringed by Teva's and Apotex's generic versions of HETLIOZ® is currently pending in the U.S. District Court for the District of Delaware. PONVORY® (ponesimod) Vanda expects to complete the transition of PONVORY® from Janssen and commercially launch the product for multiple sclerosis in the third quarter of 2024. Vanda is initiating a host of commercial activities including the creation of a specialty sales force, a prescriber awareness program and a comprehensive marketing program. Currently approved as a once-a-day oral treatment for people with multiple sclerosis, PONVORY® has a differentiated profile from other drugs in the class with high specificity and rapid reversibility, making for a versatile use to address the needs of people with multiple sclerosis and exclusivity is expected to last into the 2040s. Positive results from a Phase II clinical study for PONVORY® in the treatment of psoriasis were previously published in Lancet where PONVORY® demonstrated significant effects in both induction and maintenance of response.3 Vanda expects to file an Investigational New Drug (IND) application with the FDA for PONVORY® in the treatment of psoriasis. Vanda expects to initiate a Phase III study for PONVORY® in the treatment of psoriasis by the end of 2024. If ultimately approved for marketing, PONVORY® would be the first oral sphingosine-1-phosphate (S1P) analog approved for the treatment of psoriasis and would significantly expand the addressable patient population of PONVORY®, with over 8 million people diagnosed with psoriasis in the U.S.4 Vanda expects to file an IND application with the FDA for PONVORY® in the treatment of ulcerative colitis. Vanda expects to initiate a Phase III study for PONVORY® in the treatment of ulcerative colitis by the end of 2024. If ultimately approved for marketing, PONVORY® would follow other oral sphingosine-1-phosphate (S1P) analogs approved for the treatment of ulcerative colitis and would significantly expand the addressable patient population of PONVORY®, with an estimated prevalence in the U.S. of approximately 2 million individuals.5 Tradipitant The NDA for tradipitant for the treatment of symptoms of gastroparesis is under review by the FDA with a PDUFA target action date of September 18, 2024. Gastroparesis is a significant unmet medical need with the last treatment option approved over 40 years ago and an estimated prevalence in the U.S. of over 6 million individuals.6 The second Phase III clinical study of tradipitant in the treatment of motion sickness is fully enrolled and results are expected in the second quarter of 2024. The efficacy of tradipitant in the treatment of motion sickness has previously been demonstrated in two clinical studies in which tradipitant was effective in preventing vomiting associated with motion. Vanda expects to submit an NDA for the treatment of motion sickness to the FDA in the fourth quarter of 2024. An eventual NDA approval of tradipitant in the treatment of motion sickness would significantly expand the addressable patient population, with approximately 30% of the U.S. population reported to suffer from motion sickness under ordinary travel conditions that include sea, air and land.7 Early-Stage Programs The Phase II study of VSJ-110 for the treatment of dry eye is ongoing and more than 50% enrolled. The Phase I clinical study for VCA-894A in the treatment of a patient with Charcot-Marie-Tooth disease, axonal, type 2S (CMT2S), an inherited peripheral neuropathy for which there is no available treatment, expects to enroll the patient in mid-2024. The Phase I clinical study of VTR-297 for the treatment of onychomycosis, a fungal infection of the nail, was initiated in April 2024. VQW-765, an alpha-7 nicotinic acetylcholine receptor partial agonist, is currently in clinical development for treatment of acute performance anxiety in social situations. GAAP Financial Results Net loss was $4.1 million in the first quarter of 2024 compared to net income of $3.3 million in the first quarter of 2023. Diluted net loss per share was $0.07 in the first quarter of 2024 compared to diluted net income per share of $0.06 in the first quarter of 2023. 2024 Financial Guidance Given continuing uncertainties surrounding the U.S. market for HETLIOZ® for the treatment of Non-24 as a result of continued generic competition in the U.S. and the upcoming commercial launches for Fanapt® in acute bipolar I disorder and PONVORY® in multiple sclerosis, Vanda is unable to provide 2024 financial guidance at this time. Conference Call Vanda has scheduled a conference call for today, Wednesday, May 8, 2024, at 4:30 PM ET. During the call, Vanda's management will discuss the first quarter 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 2594340. A replay of the call will be available on Wednesday, May 8, 2024, beginning at 8:30 PM ET and will be accessible until Wednesday, May 15, 2024 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 2594340. 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 Calhoun SL, Fernandez-Mendoza J, Vgontzas AN, Liao D, Bixler EO. Prevalence of insomnia symptoms in a general population sample of young children and preadolescents: gender effects. Sleep Med. 2014 Jan;15(1):91-5. doi: 10.1016/j.sleep.2013.08.787. Epub 2013 Oct 16. PMID: 24333223; PMCID: PMC3912735. Fricke-Oerkermann L, Plück J, Schredl M, Heinz K, Mitschke A, Wiater A, Lehmkuhl G. Prevalence and course of sleep problems in childhood. Sleep. 2007 Oct;30(10):1371-7. doi: 10.1093/sleep/30.10.1371. PMID: 17969471; PMCID: PMC2266270. Vaclavkova A, Chimenti S, Arenberger P, Holló P, Sator PG, Burcklen M, Stefani M, D'Ambrosio D. Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2014 Dec 6;384(9959):2036-45. doi: 10.1016/S0140-6736(14)60803-5. Epub 2014 Aug 10. PMID: 25127208. Datamonitor Healthcare – Psoriasis Patient-Based Market Forecast published March 2023. Datamonitor Healthcare – Ulcerative Colitis Patient-Based Market Forecast published March 2023. Rey et al J Neurogastroenterol Motil, Jan 2012. Turner M, Griffin MJ. Motion sickness in public road transport: passenger behavior and susceptibility. Ergonomics. 1999: 42: 444-461. 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, statements regarding the advancement of Vanda's clinical development pipeline and strengthening of its commercial presence, Vanda's plans for pursuit of FDA approval of tradipitant in the treatment of symptoms of gastroparesis and the treatment of motion sickness, HETLIOZ® in the treatments of insomnia and jet lag disorder, Vanda's expectations regarding the timing of the FDA's decisions with respect to the sNDAs for HETLIOZ® and the NDA for tradipitant, Vanda's plans for a LAI formulation of Fanapt®, the timing of a submission of an NDA for milsaperidone, the potential for PONVORY® to treat psoriasis and ulcerative colitis, the planned patient enrollment for a clinical study for VCA-894A, the planned launch of PONVORY® in the US and the ongoing launch of Fanapt® in acute bipolar I disorder, the planned clinical programs to test Fanapt® and milsaperidone in depressive symptoms and the planned Hetlioz LQ® program in pediatric insomnia 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 complete the clinical development of the products in its pipeline and obtain regulatory approval and market acceptance of these products, Vanda's ability to obtain FDA approval of the sNDAs for HETLIOZ® and the NDA for tradipitant, the FDA's ability to meet the PDUFA target action date for the NDA for tradipitant, the FDA's assessment of the sufficiency of the data packages included in Vanda's regulatory submissions for HETLIOZ® and tradipitant, Vanda's ability to obtain approval for milsaperidone in the treatment of schizophrenia and acute bipolar I disorder, the results of any clinical trials conducted for PONVORY® in the treatment of other inflammatory/autoimmune disorders, Vanda's ability to obtain regulatory approval of HETLIOZ® and PONVORY® for any additional indications, Vanda's ability to complete the clinical program for tradipitant in the treatment of motion sickness, the planned clinical programs to test Fanapt® and milsaperidone in depressive symptoms and Vanda's ability to execute the planned launch of PONVORY® in the US and ongoing launch of Fanapt®. 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.

Phase 2Phase 1Phase 3Clinical ResultNDA

23 Apr 2024

·www.biospace.com

Supreme Court Denies Vanda’s Petition in Hetlioz Patent Case Against Teva

Pictured: The U.S. Supreme Court building in Washington, DC/iStock, SeanPavonePhoto The U.S. Supreme Court will not hear Vanda Pharmaceuticals’ petition in its patent case against Teva Pharmaceuticals regarding its sleep-wake disorder drug Hetlioz (tasimelteon), according to an order list published Monday. Vanda CEO Mihael H. Polymeropoulos in a statement said that the company is “disappointed” by the Supreme Court’s decision to not hear the case, adding that the biotech is nevertheless “pleased” that the case “has drawn attention to an area of law that has broad and significant implications in life sciences innovation.” Designed to be orally available, Hetlioz is a small molecule agonist of the melatonin MT1 and MT2 receptors, both of which are central to circadian rhythm control. The drug was approved in 2014 for the treatment of non-24-hour sleep-wake disorder. Vanda filed its lawsuit in 2018 after Teva announced that it had submitted an Abbreviated New Drug Application to the FDA for a generic version of Hetlioz. At the time, Teva told Vanda that many of its patents covering Hetlioz are “invalid, unenforceable and/or will not be infringed.” However, Vanda alleged that Teva had infringed these patent protections. In December 2022, a Delaware federal court not only rejected Vanda’s infringement claims but also found that four of its patents were invalid. The U.S. Court of Appeals for the Federal Circuit upheld this decision in 2023 and in October of the same year, Vanda announced that it intended to petition for a writ of certiorari. “Vanda believes that the Federal Circuit’s approach improperly invalidates critical patent rights, which are necessary to ensure robust pharmaceutical research and development,” the biotech noted at the time. The company formally filed its petition in January 2024. In its petition, Vanda argued that the Federal Circuit’s decision “threatens to render many advancements in drug development unpatentable,” according to Reuters. "That is an especially pernicious result for rare diseases, where patent-based incentives are crucial for innovators to invest the billions required to develop new, successful treatments." Monday’s Supreme Court snub delivers another blow to Hetlioz, which last month suffered an FDA rejection. Vanda was proposing Hetlioz for the treatment of insomnia. In addition to Hetlioz, Vanda also owns Fanapt (iloperidone), an atypical antipsychotic medication that won the FDA’s approval earlier this month for the treatment of manic or mixed episodes in bipolar I disorder. Fanapt is also indicated for schizophrenia, for which the drug was approved in 2009. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Drug ApprovalPatent Infringement

22 Apr 2024

·www.fiercepharma.com

US Supreme Court rejects Vanda's bid to revive patents on sleep disorder drug Hetlioz

For all of 2023, Hetlioz generated slightly more than $100 million in sales, representing a steep 37% decline from the $159.7 million it brought home in 2022. The prospects for Vanda Pharmaceuticals’ 10-year-old circadian rhythm drug Hetlioz have grown that much dimmer after the U.S. Supreme Court shot down the company’s attempt to challenge an appeals court decision invalidating several of the drug’s patents in 2023. The High Court has rebuffed (PDF) Vanda’s bid to contest the May 2023 ruling from the U.S. Court of Appeals for the Federal Circuit roughly four months after the company appealed to the Supreme Court to review the decision, according to a SCOTUS order list published Monday. Vanda first sued Israeli-American pharma Teva and Canada-based Apotex in Delaware back in 2018, alleging the generic drug makers had tread on certain Hetlioz patents after applying to make copycats of the med, which was first approved by the FDA in 2014 to treat non-24-hour sleep-wake disorder. In December 2022, the Delaware federal court both rejected Vanda’s infringement claims and took things a step further by ruling that four of Vanda’s patents were invalid. An appeals court upheld the decision in 2023, prompting Vanda to seek the Supreme Court’s aid in January, Reuters reports. "We are disappointed that the Supreme Court has decided not to hear our case and clarify the lower court standard for obviousness in patent law," Mihael H. Polymeropoulos, president, CEO and chairman of Vanda's board said in a statement. "However, we are pleased that our case has drawn attention to an area of law that has broad and significant implications in life sciences innovation." The failure of Vanda’s legal Hail Mary will likely take a heavy toll on the company and the future success of its decade-old drug. For all of 2023, Hetlioz generated slightly more than $100 million in sales, representing a steep 37% decline from the $159.7 million it brought home in 2022. In its most recent earnings report, Vanda blamed (PDF) the sales falloff on the Hetlioz generic launches in the U.S. Aside from Hetlioz, Vanda also markets the schizophrenia and bipolar disorder drug Fanapt as well as the multiple sclerosis drug Ponvory. Vanda shelled out $100 million in December to pick up U.S. and Canadian rights to Ponvory from Johnson & Johnson’s Actelion subsidiary. Vanda’s total 2023 revenues clocked in at $192.6 million, of which Hetlioz sales accounted for slightly more than 50%. Vanda’s Monday share price was down about 4.3% on news of the Supreme Court rejection. Meanwhile, this marks the second major setback for Hetlioz this year. In early March, the FDA denied Vanda’s request for a hearing over the regulator’s 2019 rejection of Hetlioz in jet lag disorder. Separately, Vanda revealed around the same time that the FDA had also swatted down its expansion bid for Hetlioz in insomnia. That second rejection came after the FDA in February alerted Vanda it had identified shortcomings in the drug’s insomnia application that “precluded discussion of labeling and postmarketing requirements/commitments,” Vanda said in a release at the time. Still, it hasn’t all been bad for Vanda this year. Earlier this month, the FDA signed off on the company’s Fanapt tablets to treat adults with manic or mixed episodes associated with bipolar I disorder. Fanapt, also known as iloperidone, started its development journey in the mid-1990s, ping-ponging between Novartis and Titan Pharmaceuticals before Vanda acquired the drug in 2004. The FDA rejected the drug in 2008 but ultimately approved iloperidone in schizophrenia in 2009 under the Fanapt moniker. Elsewhere, Vanda last week parried a hostile takeover bid by Future Pak to acquire the Washington, D.C.-based company at what Vanda claimed was a discount to its “intrinsic value.” Vanda managed to ward off the takeover attempt through what’s known as a “poison pill”—an approach that works by imposing a significant penalty on any person or group that acquires ownership of 10% or more of its shares of common stock without prior approval of the company’s board. Editor's note: This story has been updated with comments from Vanda.

Drug ApprovalAcquisition

100 Deals associated with Iloperidone

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KEGG	Wiki	ATC	Drug Bank
D02666	Iloperidone	N05AX14	DB04946

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Bipolar I disorder	US	Vanda Pharmaceuticals, Inc.	02 Apr 2024
Mania	US	Vanda Pharmaceuticals, Inc.	02 Apr 2024
Schizophrenia	US	Vanda Pharmaceuticals, Inc.	06 May 2009

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute schizophrenia	Phase 3	US	Vanda Pharmaceuticals, Inc.	01 Nov 2005
Acute schizophrenia	Phase 3	IN	Vanda Pharmaceuticals, Inc.	01 Nov 2005
Osteoarthropathy, Primary Hypertrophic	Phase 2	US	Vanda Pharmaceuticals, Inc.	01 Jun 2022
Parkinson Disease	Phase 2	US	Vanda Pharmaceuticals, Inc.	01 Jun 2022
Psychotic Disorders	Phase 2	US	Vanda Pharmaceuticals, Inc.	25 Aug 2021
Irritable Mood	Phase 2	US	Novartis Pharmaceuticals Corp.	01 Jul 2013
Sleep Initiation and Maintenance Disorders	Phase 2	US	Novartis Pharmaceuticals Corp.	01 Jul 2013
Stress Disorders, Post-Traumatic	Phase 2	US	Novartis Pharmaceuticals Corp.	01 Jul 2013
Liver Diseases	Phase 1	US	Novartis Pharmaceuticals Corp.	01 Aug 2010

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04819776 (CTgov)	Phase 3	Bipolar I disorder \| Mania	417	Iloperidone (Iloperidone)	zrevohshmr(lqwviqcpgh) = rivauutnxs oqtutlhzqa (vmcgahbear, zxenpvflhn - eyieidmayx) View more	-	16 Apr 2024
				Iloperidone Placebo (Placebo)	zrevohshmr(lqwviqcpgh) = gwsqzqkynq oqtutlhzqa (vmcgahbear, jlwxqrevnd - hkzohkzvbg) View more
NCT01291511 (REPRIEVE, CTgov)	Phase 3	Schizophrenia	635	Iloperidone (Iloperidone)	asxnuxvmro(kovzxdiwdx) = yutfpndkgu dpowztrlej (qikliscbwg, yffwhfpitp - kekcjtcntp) View more	-	17 Jul 2023
				Placebo (Placebo)	asxnuxvmro(kovzxdiwdx) = awnerzngeg dpowztrlej (qikliscbwg, vkgkeflqnc - tmqbnwopmw) View more
NCT01917318 (CTgov)	Phase 2	Sleep Initiation and Maintenance Disorders \| Stress Disorders, Post-Traumatic \| Irritable Mood	1	Placebo+Iloperidone (Iloperidone / Placebo)	etnmuifcvu(kcfpufzjdq) = kobsrbivir lukvnpwbqe (jlqzdipjbu, dfqycmpwwc - ycvvpysqfa) View more	-	31 Jan 2020
				Placebo+Iloperidone (Placebo / Iloperidone)	mavktywzze(tmlhjvyzks) = kdgbplczzy osfaycxxcq (twtobhiqla, uubwwsuczu - yrfgjaekja) View more
NCT01920802 (CTgov)	Phase 4	-	31	olanzapine (Olanzapine)	wfaryxzmys(jhtuvhjkcs) = mieazoycxh wsypurhhrf (xdlflaciov, yyylltvfpk - jchejpgflc) View more	-	20 Mar 2017
				iloperidone (Iloperidone)	wfaryxzmys(jhtuvhjkcs) = zdtpskqtdy wsypurhhrf (xdlflaciov, dbehhkfipm - fphxigfnlm) View more
NCT01291511 (REPRIEVE, Pubmed \| CNS Drugs) Manual	Phase 3	Schizophrenia	303	Iloperidone	hfczpptaxp(xmebeyahpt) = gxdzjuncqr stoaksqupz (apcnzfykmy ) View more	Positive	01 Aug 2016
				Placebo	hfczpptaxp(xmebeyahpt) = zlkxqafluv stoaksqupz (apcnzfykmy ) View more
NCT01929889 (CTgov)	Phase 4	Schizoaffective disorder \| Schizophrenia	19	Iloperidone	zkeprkgvkz(cmloxtasyy) = oxagjeoexa mubxlsdsvu (gsqrgsiozn, obhfnaxfyc - qjmgwwqcmf) View more	-	10 Jul 2015
NCT01207414 (CTgov)	Phase 4	Schizophrenia	501	iloperidone (Iloperidone Gradual Switch)	afhglasncp(ojfkrsthqh) = kltrsmimjz rwyxdbnpaf (pjscyaqnmh, vziwgqeteq - virkxzpzis) View more	-	15 Mar 2013
				iloperidone (Iloperidone Immediate Switch)	afhglasncp(ojfkrsthqh) = uzqqynolwc rwyxdbnpaf (pjscyaqnmh, tkybhnnzuu - stwwtyguqr) View more

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