Multi-center, Randomized, Double-blind, Parallel-group, Double-dummy, Active-controlled, Comparative Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Ponesimod Versus Fingolimod During 108 Weeks of Treatment in Pediatric Participants, 10 to <18 Years Old, with Relapsing-remitting Multiple Sclerosis

Start Date22 Feb 2023

Sponsor / Collaborator

Janssen-Cilag International NV

NCT05552196

/ CompletedPhase 1

A Phase 1, Open-label, Parallel-group Study to Assess the Effect of Steady-state Carbamazepine on the Pharmacokinetics of Ponesimod in Healthy Adult Participants

The purpose of this study is to evaluate the effect of steady-state carbamazepine (CBZ; a strong pregnane X receptor [PXR] agonist) on the pharmacokinetics (PK) of ponesimod following a gradual up-titration regimen in healthy adult participants.

Start Date18 Oct 2022

Sponsor / Collaborator

Janssen Pharmaceutica NV

NCT05688436

/ RecruitingNot Applicable

Pregnancy Outcomes in Women Exposed to Diroximel Fumarate

In this study, researchers will learn more about the effects of diroximel fumarate (DRF), also known as VUMERITY®, when taken during pregnancy in people with multiple sclerosis, also known as MS. In MS, the immune system attacks the nerves in the brain and spinal cord. The affected areas are called lesions. The damage makes it difficult for the brain and spinal cord to function and send messages throughout the body. MS can be a progressive disease, which means it may get worse over time. In relapsing forms of MS (RMS), new symptoms may happen, and existing symptoms may get better or worse over time. DRF is an approved drug that is used to treat people with RMS.
This is known as an "observational" study, which collects health information about study participants without changing their medical care. The main goal of this study is to collect birth and health information from 3 groups of participants and their babies. These groups are:
* Those who took DRF during their pregnancy
* Those who took other drugs for RMS during their pregnancy, but not DRF
* Those who did not take any drugs for RMS during their pregnancy
The main question researchers want to learn about in this study is:
• How many participants' babies were born with major congenital malformations (MCMs)? MCMs are problems with how a baby's body forms before birth.
Researchers will also learn more about:
* Loss of the baby before 20 weeks of pregnancy
* Loss of the baby at and after 20 weeks of pregnancy
* How many babies are born early (at or before 37 weeks)
* How many babies are small for their age while in the participant's uterus
* How many babies are born with any sign of life
This study will be done as follows:
* Participants with RMS can join this study if they become pregnant from 29th October 2019 to 31st July 2030. Information will start being collected when the participant decides to join the study.
* The participants' medical records will be reviewed 2 times during the study - once when the study is halfway done, and one at the end of the study.
* Each participant will be in the study until the end of their pregnancy. Each baby will be in the study for up to 1 year after birth.
* The study is planned to end by 30th April 2031.

Start Date24 Sep 2021

Sponsor / Collaborator

Biogen, Inc.

100 Clinical Results associated with Ponesimod

100 Translational Medicine associated with Ponesimod

100 Patents (Medical) associated with Ponesimod

144

Literatures (Medical) associated with Ponesimod

01 Dec 2025·Lancet Regional Health-Europe

The effect of disease-modifying therapies on brain volume loss and disability accumulation in multiple sclerosis: a systematic review and network meta-analysis

Article

Author: Cagol, Alessandro ; Schaedelin, Sabine ; Sormani, Maria Pia ; Pretzsch, Roxanne ; Granziera, Cristina ; Kappos, Ludwig

Background:

Multiple treatments have demonstrated efficacy in preventing brain volume loss (BVL) in randomized controlled trials (RCTs) for multiple sclerosis (MS). However, assessing their relative effectiveness remains challenging due to limited head-to-head comparisons. Additionally, the relationship between treatment effects on BVL and disability accumulation is not established for newer therapies. This study aimed to compare the efficacy of approved disease-modifying therapies (DMTs) in reducing BVL in MS and to investigate the association between treatment effects on BVL and disability accumulation.

Methods:

In this systematic review and network meta-analysis, we included all RCTs enrolling adults with MS that evaluated FDA-approved DMTs and reported BVL outcomes over at least one year. We searched PubMed, Embase, and Cochrane from inception to September 2024. Following PRISMA guidelines, two reviewers independently extracted data on BVL, MRI lesion activity, and disability progression. We conducted a mixed-effects network meta-analysis with placebo as the reference group. Meta-regression analyses examined the association between treatment effects on BVL and disability progression, adjusting for MRI lesion activity.The primary outcome was BVL. Secondary outcomes included MRI lesion accumulation and risk of confirmed disability progression. Effect sizes were reported as the ratio of means (ROM) and hazard ratios (HRs), with 95% confidence intervals (CIs). This study is registered with PROSPERO (CRD420251034936).

Findings:

We included 33 RCTs evaluating 16 DMTs and 26,247 patients. Eight DMTs significantly reduced BVL compared to placebo, including ponesimod (ROM = 0.52; 95%-CI: 0.35-0.77), ofatumumab (ROM = 0.58; 95%-CI: 0.40-0.83), alemtuzumab (ROM = 0.63; 95%-CI: 0.49-0.83), teriflunomide (ROM = 0.71; 95%-CI: 0.52-0.97), ozanimod (ROM = 0.74; 95%-CI: 0.56-0.98), natalizumab (ROM = 0.77; 95%-CI: 0.61-0.96), siponimod (ROM = 0.77; 95%-CI: 0.60-0.98), and fingolimod (ROM = 0.83; 95%-CI: 0.71-0.96). The treatment effect on BVL was associated with the treatment effect on disability accumulation (β = 0.466; p = 0.008), and this association remained significant independently of the treatment effect on MRI activity (β = 0.422; p = 0.005).

Interpretation:

Several DMTs-including newer therapies-significantly reduce BVL, and this effect correlates with reduced disability accumulation. These findings support BVL as a meaningful treatment target in MS.

Funding:

None.

01 Dec 2025·Multiple Sclerosis and Related Disorders

Suboptimal dose of approved disease modifying therapies in management of patients with multiple sclerosis: A systematic review

Review

Author: Sahraian, Mohammad Ali ; Paybast, Sepideh ; Baghalha, Fatemeh

BACKGROUND:

Multiple sclerosis (MS) is the most common immune-mediated neurodegenerative disorder of the central nervous system (CNS). Suboptimal dosing of disease-modifying treatment (DMT) has emerged as an issue of interest in recent years. Herein, we investigated the clinical efficacy and safety issues of approved DMTs for patients with relapse-remitting MS (RRMS).

METHOD:

This systematic review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Electronic databases of PubMed, Embase, Scopus, and Web of Science were systematically searched from inception to 27 July 2025. Relevant studies on the clinical efficacy and safety of suboptimal dosages of approved DMTs were considered for data synthesis.

RESULTS:

Out of 11,568 records, 34studies met the inclusion criteria. A total of 527 patients on standard dose compared to 502 patients on the suboptimal dose of interferon-ß,558 patients on standard dose compared to 576 patients on the suboptimal dose of fingolimod, 145 patients on standard dose compared to 139 patients on suboptimal dose of ponesimod, 4944 patients on standard dose compared to 3689 patients on suboptimal dose of natalizumab, and 947 patients on standard dose compared to 836 patients on suboptimal dose of ocrelizumab were evaluated. Main reasons for choosing a suboptimal strategy included the reduction of potential adverse events associated with the DMTs, such as injection reaction for interferon-ß, lymphopenia and elevated enzyme levels for fingolimod, progressive multifocal leukoencephalopathy risk for natalizumab, and an increased risk of infection and hypogammaglobulinemia for ocrelizumab. The primary suboptimal dosing strategies included reducing the dose and extending the dosing interval (EID) for interferon-ß, non-daily dosing for fingolimod, and EID for natalizumab and ocrelizumab. While the suboptimal dosing strategy successfully reduced adverse events, the results were equivocal in terms of efficacy, with most evidence showing similar efficacy of the EID every six weeks of natalizumab and EID (6 months + ≥ 4 weeks) of ocrelizumab compared with the standard dose.

CONCLUSION:

Suboptimal dosing of DMTs in MS is a growing treatment strategy to enhance patient adherence and reduce adverse events. Future prospective studies are necessary to establish the safety and efficacy of suboptimal dosing protocols for different classes of DMTs in MS management.

01 Nov 2025·EUROPEAN JOURNAL OF NEUROLOGY

Recent Advances in Interventions Targeting Remyelination and a Systematic Review of Remyelinating Effects of Approved Disease‐Modifying Treatments for Multiple Sclerosis

Review

Author: El Ouaamari, Yousra ; Reynders, Tatjana ; Wens, Inez ; Popescu, Veronica ; Cambron, Melissa ; D'Haeseleer, Miguel ; Willem, Lander ; De Keersmaecker, Anna‐Victoria ; van Doninck, Eline ; Derdelinckx, Judith ; Laureys, Guy ; Willekens, Barbara

ABSTRACT:

Background:

Regenerative strategies in progressive multiple sclerosis (MS) pose a significant unmet need. Combining immunomodulatory treatment with remyelinating interventions to target the complex underlying pathogenesis appeals as the next frontier in MS therapeutic developments. Therefore, it is important to identify which disease‐modifying treatments (DMT) with proremyelinating properties are most promising for future use in combination treatments. This systematic review provides an overview of preclinical and clinical research on remyelination, focusing on the effects of currently available FDA and EMA‐approved DMT .

Methods:

The search was conducted in accordance with the “Synthesis without meta‐analysis” (SWiM) reporting guideline. The protocol was registered at PROSPERO prior to the search.

Results:

Fifty‐seven articles on preclinical research, three randomized controlled trials (RCTs), 29 non‐randomized clinical studies, and eight reviews were included. Preclinical research suggested neuroprotective properties of various DMT. However, convincing evidence of true remyelination, either by influencing oligodendrocyte lineage cells in cell cultures or histological analysis in vivo, could only be found in studies investigating glatiramer acetate, teriflunomide, Fingolimod, Siponimod, Ponesimod, and alemtuzumab. Clinical trials using surrogate markers of myelin repair, such as advanced imaging and electrophysiological techniques, demonstrated promising results with glatiramer acetate, Fingolimod, Siponimod, natalizumab, alemtuzumab, and ocrelizumab. However, we found insufficient proof to claim that changes in these surrogate markers can be explained by remyelination alone.

Conclusions:

Future proof‐of‐concept clinical trials investigating remyelinating agents in MS should consider combining outcome measures into composite endpoints. Furthermore, research efforts should be dedicated to novel biomarkers to assess repair mechanisms in MS.

News (Medical) associated with Ponesimod

02 Jan 2026

·www.fiercepharma.com

Vanda's motion sickness drug, Agios' thalassemia treatment make the grade with FDA

Over the holidays, the FDA gave thumbs up to Vanda Pharmaceuticals' motion sickness pill Nereus and to Agios Pharmaceuticals' thalassemia treatment Aqvesme. The FDA delivered a pair of holiday season approvals a week apart, signing off on Agios’ oral medicine Aqvesme for the treatment of anemia in adults with alpha- or beta-thalassemia on Dec. 23, and then issuing its final new drug approval of the year to Vanda Pharmaceuticals for motion sickness pill Nereus on Dec. 30.As has been the case with many FDA decisions in this year of cutbacks and leadership transition, neither nod was accomplished easily.The endorsement for Agios came after the FDA shifted its decision date from Sept. 7 to Dec. 7, needing additional time to review the company’s Risk Evaluation and Mitigation Strategy (REMS) to mitigate potential liver injury that comes with the use of Aqvesme (mitapivat). Then, in early December, the company explained that there was another decision delay as it was working with the agency to “finalize the labeling documents” for its REMS plan.As for Vanda, its approval arrived after the FDA lifted a partial clinical hold on Dec. 4, concluding that motion sickness is not a chronic condition and that Nereus (tradipitant) is an “acute, event-driven therapy.” With that, the U.S. regulator determined that a six-month toxicity study of tradipitant was not necessary. Agios’ 2nd nod for mitapivatThis is not Agios’ first go-round with the FDA on mitapivat. Nearly four years ago, the agency blessed it with the commercial name Pyrukynd as the first treatment to reduce hemolytic anemia in adults with the rare, genetic blood disorder pyruvate kinase (PK) deficiency.The endorsement for twice-daily Aqvesme opens the treatment up to a larger patient population, including those with non-transfusion-dependent or transfusion-dependent alpha- or beta-thalassemia. It relieves patients from the burden of transfusions or subcutaneous treatments. It is also the “first medicine to show quality of life improvements in non-transfusion-dependent patients, which we understand to be of critical importance,” Agios CEO Brian Goff said in a Christmas Eve conference call. The company will make Aqvesme available in late January after its REMS program is implemented, Agios said. It will charge $425,000 for a yearly supply of Aqvesme, which is up from the $335,000 wholesale acquisition cost of Pyrukynd. The separate brand names for mitapivat allows Agios to “isolate the Aqvesme REMS to thalassemia, ensuring regulatory clarity and confirming that it does not apply to Pyrukynd for PK deficiency,” Goff added.The label of Aqvesme will include a boxed warning for hepatocellular injury. The REMS program will require patients to undergo liver testing before beginning treatment and then every four weeks of the next 24 weeks after initiating its use.Agios reported sales of Pyrukynd reached $34 million for the first three quarters of 2025, with 149 patients on therapy in the third quarter, up from 136 in the first quarter. The company estimates the addressable thalassemia patient population at 4,000 in the U.S. Vanda scores with NereusThe FDA motion sickness blessing for Nereus comes 15 months after the FDA rejected the oral neurokinin-1 (NK-1) receptor antagonist to reduce nausea and vomiting in patients with the digestive disorder gastroparesis.The complete response letter (CRL) triggered a fiery response from the Washington, D.C.-based drugmaker, which blasted the agency for the delay in its decision and for not conducting an advisory committee meeting to discuss the treatment's value. Nereus made the grade, however, as the FDA blessed it to reduce the incidence of motion-induced vomiting. With the nod, Nereus has become the first new pharmacologic treatment for the condition in more than four decades, the drugmaker said.The approval was backed by three phase 3 trials, including two conducted on boats, which showed that it reduced nausea in participants with a history of motion sickness. In one boat study of 365 participants, there was a 19% incidence of vomiting of those on Nereus compared to a 44% incidence for those on placebo. Vanda said it will make Nereus available in the “coming months.” It becomes the fourth drug on the market for Vanda, which scored a 2009 approval for schizophrenia treatment Fanapt, followed by a 2024 expansion to treat bipolar I disorder. The new indication helped Vanda boost sales of Fanapt to $84 million over the first nine months of 2025, a 24% year-over-year increase.Vanda also sells sleep disorder drug Hetlioz, which reached the market in 2014, and relapsing multiple sclerosis treatment Ponvory, which was approved in 2021. The FDA is scheduled on Jan. 7 to decide on Vanda’s Hetlioz as a treatment for jet lag disorder.As for tradipitant, Vanda hasn’t surrendered its effort to get it across the FDA finish line for gastroparesis. Vanda also is studying tradipitant to prevent nausea and vomiting induced by GLP-1 obesity drugs.

Drug ApprovalPhase 3Acquisition

15 Dec 2025

·www.prnewswire.com

Vanda Announces Submission of Biologics License Application to the FDA for Imsidolimab for the Treatment of Generalized Pustular Psoriasis

WASHINGTON, Dec. 15, 2025 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for imsidolimab, a novel IgG4 IL-36 receptor antagonist, to treat generalized pustular psoriasis (GPP). Imsidolimab inhibits IL-36 receptor signaling, addressing the deficiency in the endogenous IL-36RA regulator commonly seen in GPP patients due to IL36RN gene mutations. The BLA is supported by positive results from the global Phase 3 GEMINI-1 and GEMINI-2 studies, where a single intravenous dose of imsidolimab led to rapid disease clearance, achieving clear or almost clear skin, with efficacy maintained throughout an approximately 2-year maintenance study period with monthly doses. Imsidolimab demonstrated a favorable safety profile with no clinically meaningful safety signals. GPP is a rare, chronic, life-threatening autoinflammatory skin disorder characterized by sudden flares of widespread pustules, erythema, and systemic symptoms such as fever and fatigue. Driven primarily by loss-of-function mutations in IL36RN, GPP represents a significant unmet medical need, with prevalence estimates varying widely by region, ranging from approximately 2 to 124 cases per million worldwide (e.g., lower in Europe and higher in parts of Asia).1,2,3,4 "The submission of the BLA for imsidolimab marks a critical milestone in our efforts to bring this innovative therapy to patients suffering from GPP," said Mihael H. Polymeropoulos, M.D., President, CEO and Chairman of the Board of Vanda Pharmaceuticals. "Imsidolimab builds on our growing expertise in rare orphan disorders and our anti-inflammatory portfolio, including Ponvory®, which is approved for the treatment of relapsing forms of multiple sclerosis and is in clinical development for the treatment of psoriasis and ulcerative colitis. We look forward to potential FDA approval and leveraging our commercial infrastructure to address this debilitating condition." Vanda has requested priority review for the BLA, citing GPP's status as a rare orphan disease with significant unmet need. If granted, priority review would establish a six-month review cycle, with a potential FDA approval of imsidolimab for the treatment of GPP as early as mid-2026. References: Prinz, J. C. et al. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review. Journal of the European Academy of Dermatology and Venereology 37, 256–273 (2022). Marrakchi, S. et al. Interleukin-36–Receptor Antagonist Deficiency and Generalized Pustular Psoriasis. New England Journal of Medicine 365, 620–628 (2011). Sugiura, K. et al. The Majority of Generalized Pustular Psoriasis without Psoriasis Vulgaris Is Caused by Deficiency of Interleukin-36 Receptor Antagonist. Journal of Investigative Dermatology 133, 2514–2521 (2013). Sachen, K. L., Arnold Greving, C. N. & Towne, J. E. Role of IL-36 cytokines in psoriasis and other inflammatory skin conditions. Cytokine 156, 155897 (2022). About GEMINI-1 and GEMINI-2 Studies In the 45-patient GEMINI-1 Phase 3 trial, patients were randomized 1:1:1 to a single intravenous infusion of 750 mg imsidolimab, 300 mg imsidolimab, or placebo on Day 0. At Week 4 (primary endpoint), 53% of patients receiving either dose of imsidolimab achieved a GPPGA score of 0/1 (clear or almost clear skin), compared to 13% on placebo (p=0.0131 for 750 mg dose). Responders from GEMINI-1 were re-randomized in GEMINI-2 to monthly subcutaneous maintenance dosing with 200 mg imsidolimab or placebo, followed for up to 116 weeks. All patients on active maintenance therapy maintained clear or almost clear skin with no flares, compared to 25% maintenance and 63% flare rate in the placebo group. Across both studies, imsidolimab demonstrated a favorable safety profile, with no treatment-related serious adverse events or discontinuations due to adverse events. About Imsidolimab and GPP Imsidolimab is a fully humanized IgG4 monoclonal antibody that inhibits IL-36 receptor signaling and is being developed for GPP, a rare orphan indication. Regulatory and patent exclusivity for imsidolimab is expected to extend into the late 2030s. Vanda holds an exclusive global license for the development and commercialization of imsidolimab from AnaptysBio (Nasdaq: ANAB). GPP flares involve painful pustules over large skin areas, accompanied by redness, itching, and systemic symptoms, and can be life-threatening if untreated. 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 estimated prevalence of GPP, the potential for FDA approval of the imsidolimab BLA, the commercial availability of imsidolimab to treat patients with GPP, the potential to extend regulatory and patent exclusivity for imsidolimab into the late 2030s, and the potential timing of FDA approval of imsidolimab for the treatment of GPP, 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 accuracy of the estimates of the number of patients with GPP worldwide, Vanda's ability to obtain regulatory approval of, and successfully commercialize, imsidolimab for the treatment of GPP, Vanda's ability to satisfy the conditions necessary to extend imsidolimab's regulatory and patent exclusivity into the late 2030s and the FDA's determination that the BLA and its supporting documentation meet the criteria for priority review. Therefore, no assurance can be given that the results or developments anticipated by Vanad 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. 21% more press release views with Request a Demo

Phase 3Clinical ResultPriority ReviewLicense out/inDrug Approval

29 Oct 2025

·www.prnewswire.com

Vanda Pharmaceuticals Reports Third Quarter 2025 Financial Results

Fanapt® Q3 2025 net product sales increased by 31% to $31.2 million compared to Q3 2024 BysantiTM (milsaperidone) NDA for bipolar I disorder and schizophrenia under review by the FDA; PDUFA target action date of February 21, 2026 Tradipitant NDA for motion sickness under review by the FDA; PDUFA target action date of December 30, 2025 Imsidolimab BLA in generalized pustular psoriasis expected to be submitted in Q4 2025 Vanda announced collaborative framework with the FDA for resolution of certain disputes Re-review of Vanda's sNDA for HETLIOZ ® for the treatment of jet lag disorder by January 7, 2026 WASHINGTON, Oct. 29, 2025 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced financial and operational results for the third quarter ended September 30, 2025. "This quarter reflects strong commercial execution, with total net product sales reaching $56.3 million, up 18% year-over-year, led by a 31% increase in Fanapt sales and 35% growth in prescriptions. HETLIOZ continues to deliver stable performance with $18.0 million in Q3 sales," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. "We are particularly encouraged by our advancing pipeline, with multiple near-term regulatory milestones: the tradipitant NDA for motion sickness under FDA review with a PDUFA target action date of December 30, 2025; the Bysanti NDA for bipolar I disorder and schizophrenia also under FDA review with a PDUFA target action date of February 21, 2026; and the anticipated Q4 submission of the imsidolimab BLA for generalized pustular psoriasis. We are also investing strategically in our commercial infrastructure, including increased brand visibility through targeted sponsorships, with the goal of supporting long-term market leadership and future commercial launches. We believe that these milestones, combined with our collaborative framework with the FDA, will position Vanda for sustained growth and expanded therapeutic impact in 2026 and beyond." Financial Highlights Third Quarter of 2025 Total net product sales from Fanapt®, HETLIOZ® and PONVORY® were $56.3 million in the third quarter of 2025, an 18% increase compared to $47.7 million in the third quarter of 2024. Fanapt® net product sales were $31.2 million in the third quarter of 2025, a 31% increase compared to $23.9 million in the third quarter of 2024. HETLIOZ® net product sales were $18.0 million in the third quarter of 2025, a 1% increase compared to $17.9 million in the third quarter of 2024. PONVORY® net product sales were $7.0 million in the third quarter of 2025, a 20% increase compared to $5.9 million in the third quarter of 2024. Net loss was $22.6 million in the third quarter of 2025 compared to net loss of $5.3 million in the third quarter of 2024. Cash, cash equivalents and marketable securities (Cash) was $293.8 million as of September 30, 2025, representing a decrease to Cash of $31.8 million compared to June 30, 2025. First Nine Months of 2025 Total net product sales from Fanapt®, HETLIOZ® and PONVORY® were $158.9 million in the first nine months of 2025, a 9% increase compared to $145.6 million in the first nine months of 2024. Fanapt® net product sales were $84.1 million in the first nine months of 2025, a 24% increase compared to $67.6 million in the first nine months of 2024. HETLIOZ® net product sales were $55.0 million in the first nine months of 2025, a 3% decrease compared to $56.6 million in the first nine months of 2024. PONVORY® net product sales were $19.8 million in the first nine months of 2025, a 7% decrease compared to $21.3 million in the first nine months of 2024. Net loss was $79.3 million in the first nine months of 2025 compared to net loss of $14.0 million in the first nine months of 2024. Cash was $293.8 million as of September 30, 2025, representing a decrease to Cash of $80.9 million compared to December 31, 2024. Key Operational Highlights – Commercial Fanapt® experienced significant growth, with total prescriptions (TRx)1 increasing by 35% and Fanapt® net product sales increasing by 31% in the third quarter of 2025 as compared to the third quarter of 2024. During the first nine months of 2025, Vanda's direct-to-consumer campaign, launched in the first quarter, continued to drive meaningful gains in brand awareness for the company and its products, Fanapt® and PONVORY®. The Company maintained strategic investments in its commercial infrastructure, including increased brand visibility through targeted sponsorships, with the goal of supporting long-term market leadership and future commercial launches. Key Operational Highlights – Regulatory & Clinical Development A clinical study of tradipitant in the prevention of vomiting induced by a GLP-1 analog, Wegovy® (semaglutide), is now complete. Results are expected in the fourth quarter of 2025. On October 1, 2025, Vanda announced that it had agreed on a collaborative framework with the U.S. Food and Drug Administration (FDA) for the resolution of certain disputes regarding HETLIOZ® (tasimelteon) and tradipitant. Pursuant to the agreement: The FDA will conduct an expedited re-review of the partial clinical hold preventing long term clinical studies of tradipitant for the treatment of motion sickness by November 26, 2025. The FDA will continue its review of Vanda's New Drug Application (NDA) for this indication, with the existing Prescription Drug User Fee Act (PDUFA) target action date of December 30, 2025. The FDA will conduct an expedited re-review of Vanda's supplemental New Drug Application (sNDA) for HETLIOZ® for the treatment of jet lag disorder by January 7, 2026, including consideration of alternative or narrowed indications focusing on the sleep-related aspects of jet lag disorder. Bysanti™ NDA for bipolar I disorder and schizophrenia is under review by the FDA with a PDUFA target action date of February 21, 2026. Tradipitant NDA for motion sickness is under review by the FDA with a PDUFA target action date of December 30, 2025. A Bysanti™ Phase III clinical study for use as a once-daily adjunctive treatment for major depressive disorder (MDD) is enrolling patients and results are expected in 2026. Imsidolimab Biologics License Application (BLA) in generalized pustular psoriasis (GPP) expected to be submitted to the FDA in the fourth quarter of 2025. The Phase III study of the long acting injectable formulation of iloperidone in the treatment of schizophrenia in relapse-prevention is enrolling patients. A clinical study of the long acting injectable formulation of iloperidone in people with treatment-resistant hypertension is ongoing and Vanda plans to begin enrolling patients soon. GAAP Financial Results Net loss was $22.6 million in the third quarter of 2025 compared to net loss of $5.3 million in the third quarter of 2024. Diluted net loss per share was $0.38 in the third quarter of 2025 compared to diluted net loss per share of $0.09 in the third quarter of 2024. Net loss was $79.3 million in the first nine months of 2025 compared to net loss of $14.0 million in the first nine months of 2024. Diluted net loss per share was $1.35 in the first nine months of 2025 compared to diluted net loss per share of $0.24 in the first nine months of 2024. 2025 Financial Guidance Vanda is updating its 2025 financial guidance and expects to achieve the following financial objectives in 2025: Conference Call Vanda has scheduled a conference call for today, Wednesday, October 29, 2025, at 4:30 PM ET. During the call, Vanda's management will discuss the third quarter 2025 financial results and other corporate activities. Investors can call 1-888-596-4144 (domestic) or 1-646-968-2525 (international) and use passcode number 8728050. A replay of the call will be available on Wednesday, October 29, 2025, beginning at 7:00 PM ET and will be accessible until Wednesday, November 5, 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 8728050. 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" above and statements regarding Vanda's plans for pursuit of FDA approval of BysantiTM for the acute treatment of bipolar I disorder and the treatment of schizophrenia, tradipitant for the treatment of motion sickness, and imsidolimab for the treatment of GPP, and the related timelines and prospects for approval; the goals and expected results of Vanda's commercial infrastructure investment strategy; Vanda's expectations with respect to the strength of its business; Vanda's clinical development plans and expected timelines for tradipitant in the prevention of vomiting induced by Wegovy®, BysantiTM for the treatment of MDD and the long acting injectable formulation of iloperidone in the treatments of schizophrenia in relapse-prevention and hypertension; and the actions that the FDA is expected to take, and the timing thereof, with respect to the NDA for tradipitant for the treatment of motion sickness and the sNDA for HETLIOZ® for the treatment of jet lag disorder 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 business; the FDA's ability to complete its reviews of, and reach decisions with respect to, the NDAs for Bysanti™ and tradipitant by their respective PDUFA target action dates; Vanda's ability to complete and submit the BLA for imsidolimab in the fourth quarter of 2025; Vanda's ability to achieve long-term market leadership and execute new commercial launches through its commercial infrastructure investments; Vanda's ability to complete the clinical studies for tradipitant in the prevention of vomiting induced by Wegovy® and BysantiTM for the treatment of MDD and receive results in the expected timeframes; Vanda's ability to complete enrollment of patients in the clinical study for the long acting injectable formulation of iloperidone in the treatment of schizophrenia in relapse-prevention and to begin enrolling patients in the study of the long acting injectable formulation of iloperidone for the treatment of hypertension in the expected timeframe; and the FDA's ability to conduct expedited re-reviews of the partial clinical hold on tradipitant for the treatment of motion sickness by November 26, 2025 and the sNDA for HETLIOZ® for the treatment of jet lag disorder by January 7, 2026. 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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Financial StatementPhase 3NDA

100 Deals associated with Ponesimod

External Link

KEGG	Wiki	ATC	Drug Bank
D11215	Ponesimod	L04AA	DB12016

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Multiple sclerosis relapse	United States	Vanda Pharmaceuticals, Inc.	18 Mar 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic graft-versus-host disease	Phase 2	-	Actelion Pharmaceuticals US, Inc.	29 Sep 2016
Chronic large plaque psoriasis	Phase 2	Austria	Actelion Pharmaceuticals US, Inc.	31 Oct 2010
Chronic large plaque psoriasis	Phase 2	Belgium	Actelion Pharmaceuticals US, Inc.	31 Oct 2010
Chronic large plaque psoriasis	Phase 2	Bulgaria	Actelion Pharmaceuticals US, Inc.	31 Oct 2010
Chronic large plaque psoriasis	Phase 2	Czechia	Actelion Pharmaceuticals US, Inc.	31 Oct 2010
Chronic large plaque psoriasis	Phase 2	Denmark	Actelion Pharmaceuticals US, Inc.	31 Oct 2010
Chronic large plaque psoriasis	Phase 2	France	Actelion Pharmaceuticals US, Inc.	31 Oct 2010
Chronic large plaque psoriasis	Phase 2	Hungary	Actelion Pharmaceuticals US, Inc.	31 Oct 2010
Chronic large plaque psoriasis	Phase 2	Italy	Actelion Pharmaceuticals US, Inc.	31 Oct 2010
Chronic large plaque psoriasis	Phase 2	Lithuania	Actelion Pharmaceuticals US, Inc.	31 Oct 2010

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02907177 (POINT, Pubmed \| Mult Scler Relat Disord)	Phase 3	Multiple sclerosis relapse	136	Ponesimod 20 mg+Dimethyl fumarate	dufsrsynki(wbeqzsqhcu): RR = 1.2, P-Value = 0.5252 View more	Negative	01 Oct 2025
				Placebo+Dimethyl fumarate
NCT03232073 (OPTIMUM-LT, CTgov)	Phase 3	Multiple sclerosis relapse	877	Ponesimod (Ponesimod 20 mg (Core and Extension Study))	bpfcilupsx(xzxglhxxzi) = qjdbpkrknr ctbefufzez (pfzfaeeakx, mfshawjbut - akltfbnxfa) View more	-	21 Feb 2025
				Ponesimod+Teriflunomide (Teriflunomide 14 mg (Core) Then Ponesimod 20 mg (Extension))	bpfcilupsx(xzxglhxxzi) = eqwhevbnlq ctbefufzez (pfzfaeeakx, ynmafxyqal - nytdbijgxl) View more
NCT01093326 (CTgov)	Phase 2	Multiple Sclerosis, Relapsing-Remitting	353	Ponesimod (Ponesimod 10 Milligrams (mg))	pbnlymwjqe(fzjhgxpyvs) = xljebhathv wtdggzzrhd (cfosfhvtuz, xdpxypzkcc - xbfnhewevj) View more	-	01 Oct 2024
				Ponesimod (Ponesimod 20 Milligrams (mg))	pbnlymwjqe(fzjhgxpyvs) = snbpaazbue wtdggzzrhd (cfosfhvtuz, kgxhsjurnj - dsytjrrlqm) View more
Phase 2 and 3 extension studies on ponesimod (ACTRIMS2023)	Not Applicable	-	990	Ponesimod	oyqalvcwoa(futoevcsjs) = one case of elective abortion due to ectopic pregnancy xmssaxfitn (kokpbwcyev ) View more	Positive	30 May 2023
NCT02425644 \| NCT02634307 (EVOLVE-MS-1 \| OPTIMUM, Pubmed)	Phase 3	Multiple sclerosis relapse	-	Diroximel fumarate	fsofcgcizs(iidkrbmnyn) = ravtvftwhz jnmmhbqdks (zmmonpedet )	-	08 May 2023
AAN2023	Phase 3	Multiple sclerosis relapse	567	Ponesimod 20mg	tillikcmtk(gzkdxkpgji) = xnuqdhvhcs smrocoekbv (dgtswlwuat, 1.30 - 2.31)	-	25 Apr 2023
				Teriflunomide	tillikcmtk(gzkdxkpgji) = cxxdcusrar smrocoekbv (dgtswlwuat, 1.19 - 1.82)
AAN2023	Phase 2	Rhabdomyosarcoma lymphocyte count	49	mRNA vaccines	szwgmdmbfh(llcpzvqbhe) = hbugexrvcn lnvcephpzc (ctqkhabzfo )	Positive	25 Apr 2023
				viral vector vaccines	szwgmdmbfh(llcpzvqbhe) = xoncwjvlht lnvcephpzc (ctqkhabzfo )
NCT02425644 (OPTIMUM, ECTRIMS2022)	Phase 3	neurofilament light chain (NfL)	1,123	Ponesimod	oulrnizspv(dwimqpmwqu) = crkthpitar wmpowjnzjj (vxwoyaulav )	Positive	26 Oct 2022
				Teriflunomide	oulrnizspv(dwimqpmwqu) = lhdzhhlzgd wmpowjnzjj (vxwoyaulav )
NCT02425644 (OPTIMUM, ECTRIMS2022)	Phase 3	Multiple sclerosis relapse	567	Ponesimod 20 mg	omekyvpwkv(qddgmcizqv) = jvhlmcfbyq majedyvgrr (cxdwuqpmjg, 1.30 - 2.31)	-	12 Oct 2022
NCT02425644 (OPTIMUM, ECTRIMS2022)	Phase 3	Hypovolemia	-	Ponesimod	fophokjppx(gbjgiikopv) = gcchphnygc yybfejzyme (oxratyhhrw )	-	12 Oct 2022

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