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

100 Clinical Results associated with Ponesimod

100 Translational Medicine associated with Ponesimod

100 Patents (Medical) associated with Ponesimod

132

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 ; Wens, Inez ; Reynders, Tatjana ; Cambron, Melissa ; D'Haeseleer, Miguel ; Popescu, Veronica ; 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

11 Feb 2026

·www.prnewswire.com

Vanda Pharmaceuticals Reports Fourth Quarter and Full Year 2025 Financial Results

Full year 2025 Fanapt® net product sales increased by 24% to $117.3 million compared to full year 2024 Full year 2025 total revenues increased by 9% to $216.1 million compared to full year 2024 NEREUS™ (tradipitant) approved for the prevention of vomiting induced by motion Bysanti™ (milsaperidone) NDA for bipolar I disorder and schizophrenia under review by the FDA; PDUFA target action date of February 21, 2026 WASHINGTON, Feb. 11, 2026 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced financial and operational results for the fourth quarter and full year ended December 31, 2025. "2025 showed strong momentum at Vanda, led by Fanapt, with net product sales up 24% to $117.3 million, driven by a 28% rise in total prescriptions and 149% surge in new-to-brand prescriptions - reflecting accelerating growth in schizophrenia and bipolar I disorder. We await the FDA decision on the Bysanti (milsaperidone) NDA by the February 21, 2026 PDUFA date, which would expand our psychiatry franchise in the global antipsychotic category. This category had a total addressable market estimated at approximately $20 billion in 2025," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. "The FDA approval of NEREUS (tradipitant) is a landmark - the first new oral therapy for motion-induced vomiting prevention in over 40 years - targeting a large addressable population of roughly 65–78 million U.S. adults experiencing symptoms, with tens of millions seeking relief annually. We are preparing for the NEREUS commercial launch and plan to start a Phase III program in the first half of 2026 for its use in preventing vomiting from GLP-1 analogs," continued Dr. Polymeropoulos. "We submitted the imsidolimab BLA in Q4 2025 for generalized pustular psoriasis, a rare orphan condition. With our current franchise - Fanapt, HETLIOZ, HETLIOZ LQ, and PONVORY - we expect 2026 total revenues of $230 to $260 million from these marketed products alone, providing a solid baseline. We look forward to continued growth from this portfolio, with further contributions from the NEREUS launch and potential approvals of Bysanti and imsidolimab." Financial Highlights Fourth Quarter of 2025 Total net product sales from Fanapt®, HETLIOZ® and PONVORY® were $57.2 million in the fourth quarter of 2025, an 8% increase compared to $53.2 million in the fourth quarter of 2024. Fanapt® net product sales were $33.2 million in the fourth quarter of 2025, a 25% increase compared to $26.6 million in the fourth quarter of 2024. HETLIOZ® net product sales were $16.4 million in the fourth quarter of 2025, an 18% decrease compared to $20.0 million in the fourth quarter of 2024. PONVORY® net product sales were $7.6 million in the fourth quarter of 2025, a 17% increase compared to $6.5 million in the fourth quarter of 2024. Loss before income taxes was $38.0 million in the fourth quarter of 2025 compared to a loss before income taxes of $6.5 million in the fourth quarter of 2024. Provision for income taxes was $103.2 million in the fourth quarter of 2025 compared to a benefit for income taxes of $1.6 million in the fourth quarter of 2024. The provision for income taxes in the fourth quarter of 2025 includes the impact of the recording of a valuation allowance of $113.7 million against all of Vanda's deferred tax assets, which is a non-cash charge. Cash, cash equivalents and marketable securities (Cash) was $263.8 million as of December 31, 2025, representing a decrease to Cash of $29.9 million compared to September 30, 2025. Full Year 2025 Total net product sales from Fanapt®, HETLIOZ® and PONVORY® were $216.1 million for the full year 2025, a 9% increase compared to $198.8 million for the full year 2024. Fanapt® net product sales were $117.3 million for the full year 2025, a 24% increase compared to $94.3 million for the full year 2024. HETLIOZ® net product sales were $71.4 million for the full year 2025, a 7% decrease compared to $76.7 million for the full year 2024. PONVORY® net product sales were $27.4 million for the full year 2025, a 2% decrease compared to $27.8 million for the full year 2024. Loss before income taxes was $138.6 million for the full year 2025 compared to a loss before income taxes of $22.9 million for the full year 2024. Provision for income taxes was $81.8 million for the full year 2025 compared to a benefit for income taxes of $4.0 million for the full year 2024. The provision for income taxes for the full year 2025 includes the impact of the recording of a valuation allowance of $113.7 million against all of Vanda's deferred tax assets, which is a non-cash charge. Cash was $263.8 million as of December 31, 2025, representing a decrease to Cash of $110.8 million compared to December 31, 2024. Key Operational Highlights – Commercial Fanapt® experienced significant growth, with total prescriptions (TRx)1 increasing by 36% and Fanapt® net product sales increasing by 25% in the fourth quarter of 2025 as compared to the fourth quarter of 2024. Fanapt® total prescriptions increased by 28% and Fanapt® net product sales increased by 24% for the full year 2025 as compared to the full year 2024. New to brand prescriptions (NBRx)1 increased by 108% in the fourth quarter of 2025 as compared to the fourth quarter of 2024 and increased by 149% for the full year 2025 as compared to the full year 2024. During 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. Fanapt® performance remains the focus of Vanda's commercial initiatives and encourages us to continue to invest in this differentiated medicine, and, if approved, the franchise-extending launch of Bysanti™. Key Operational Highlights – Regulatory & Clinical Development The U.S. Food and Drug Administration (FDA) has approved NEREUS™ (tradipitant), an oral neurokinin-1 (NK-1) receptor antagonist, for the prevention of vomiting induced by motion. Bysanti™ (milsaperidone) New Drug Application (NDA) for bipolar I disorder and schizophrenia is under review by the FDA, with a Prescription Drug User Fee Act (PDUFA) target action date of February 21, 2026. 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. Vanda announced positive results of a clinical study of NEREUSTM in the prevention of vomiting induced by a GLP-1 analog, Wegovy® (semaglutide). A Phase III clinical program is anticipated to be initiated in the first half of 2026. Imsidolimab Biologics License Application (BLA) in generalized pustular psoriasis (GPP) was submitted to the FDA in the fourth quarter of 2025. A Phase III study of VQW-765, an alpha-7 nicotinic acetylcholine receptor partial agonist, in the treatment of adults with social anxiety disorder has been initiated and study results are expected by the end of 2026. The Phase III study of the long acting injectable (LAI) formulation of iloperidone in the treatment of schizophrenia in relapse-prevention is enrolling patients. A clinical study of the LAI formulation of iloperidone in people with treatment-resistant hypertension is ongoing and Vanda is enrolling patients. On January 8, 2026, Vanda announced that it had received a decision letter from the FDA Center for Drug Evaluation and Research (CDER) concluding that the supplemental New Drug Application (sNDA) for HETLIOZ® (tasimelteon) for the treatment of jet lag disorder cannot be approved in the current form. This letter followed CDER's re-review of the jet lag sNDA under Vanda's collaborative framework agreement with the FDA. Vanda has requested that the FDA Commissioner resume hearing proceedings. GAAP Financial Results Net loss was $141.2 million in the fourth quarter of 2025 compared to net loss of $4.9 million in the fourth quarter of 2024. Diluted net loss per share was $2.39 in the fourth quarter of 2025 compared to diluted net loss per share of $0.08 in the fourth quarter of 2024. Net loss was $220.5 million for the full year 2025 compared to net loss of $18.9 million for the full year 2024. Diluted net loss per share was $3.74 for the full year 2025 compared to diluted net loss per share of $0.33 for the full year 2024. Provision for Income Taxes - One-Time, Non-Cash Charge Impact In the fourth quarter of 2025, Vanda determined that it is not more-likely-than-not that it will realize its existing net deferred tax assets, having reviewed both positive and negative evidence as well as expectations of future taxable income, and recorded a valuation allowance against all its deferred tax assets. As a result, the fourth quarter of 2025 provision for income taxes includes a one-time, non-cash income tax charge of $113.7 million. Excluding this one-time non-cash tax charge, our full year 2025: Effective tax rate would have increased to 23%, compared to the reported effective tax rate of negative 59%. Net loss would have decreased to $106.8 million, compared to the reported net loss of $220.5 million. Diluted net loss per share would have decreased to $1.81, compared to the reported diluted net loss per share of $3.74. Vanda provides Non-GAAP financial information, which it believes can enhance an overall understanding of its financial performance when considered together with GAAP figures. Refer to the sections of this press release entitled "Non-GAAP Financial Information" and "Reconciliation of GAAP to Non-GAAP Financial Information." 2026 Financial Guidance Due to the recent and upcoming regulatory and commercial milestones, Vanda's 2026 financial guidance is limited to revenue guidance for currently commercialized products which includes Fanapt®, HETLIOZ® and PONVORY®. Vanda expects to achieve the following financial objectives in 2026. Conference Call Vanda has scheduled a conference call for today, Wednesday, February 11, 2026, at 4:30 PM ET. During the call, Vanda's management will discuss the fourth quarter and full year 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, February 11, 2026, beginning at 8:30 PM ET and will be accessible until Wednesday, February 18, 2026 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 Non-GAAP Financial Information Vanda believes that the above Non-GAAP financial information provided in this press release can assist investors in understanding and assessing the ongoing economics of Vanda's business and reflect how it manages the business internally and sets operational goals. The Non-GAAP effective tax rate, Non-GAAP net loss and Non-GAAP dilutive EPS exclude the one-time, non-cash valuation allowance income tax charge. Vanda believes that excluding the impact of this one-time, non-cash charge better reflects the recurring economic characteristics of its business, as well as Vanda's use of financial resources and its long-term performance. These Non-GAAP financial measures, as presented, may not be comparable to similarly titled measures reported by other companies because all companies may not calculate these measures in an identical manner and, therefore, they are not necessarily an accurate measure of comparison between companies. The presentation of these Non-GAAP financial measures is not intended to be considered in isolation or as a substitute for guidance prepared in accordance with GAAP. The principal limitation of these Non-GAAP financial measures is that they exclude significant elements that are required by GAAP to be recorded in Vanda's financial statements. In addition, they are subject to inherent limitations as they reflect the exercise of judgments by management in determining these Non-GAAP financial measures. In order to compensate for these limitations, Vanda presents its Non-GAAP financial information in connection with its GAAP financial information. Investors are encouraged to review the reconciliation of our Non-GAAP financial measures to their most directly comparable GAAP financial measure. 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 "2026 Financial Guidance" above and statements regarding Vanda's plans for pursuit of FDA approval of BysantiTM for the treatments of bipolar I disorder and schizophrenia and imsidolimab for the treatment of GPP, and the related timelines and prospects for approval; Vanda's commercial launch plans for NEREUSTM for the prevention of vomiting induced by motion; the prevalence of motion-induced vomiting in the U.S. and the number of people seeking relief each year; the goals, focus and expected results of Vanda's commercial infrastructure investment strategy; Vanda's clinical development plans and expected timelines for BysantiTM for the treatment of MDD, NEREUSTM in the prevention of vomiting induced by Wegovy®, the long acting injectable formulation of iloperidone in the treatments of schizophrenia in relapse-prevention and hypertension and VQW-765 in the treatment of adults with social anxiety disorder; Vanda's plans to continue its pursuit of FDA approval of HETLIOZ® for the treatment of jet lag disorder; and Vanda's expectations with respect to the strength of its business 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 NDA for Bysanti™ by February 21, 2026; Vanda's ability to obtain regulatory approval of imsidolimab for the treatment of GPP; Vanda's ability to successfully execute the commercial launch of NEREUSTM; the accuracy of the estimates of the prevalence of motion-induced vomiting in the U.S. and the number of people seeking relief each year; 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 study for BysantiTM for the treatment of MDD and receive results in 2026; Vanda's ability to initiate the clinical program for NEREUSTM in the prevention of vomiting induced by Wegovy® in the first half of 2026; Vanda's ability to complete enrollment of patients in the clinical studies for the LAI formulation of iloperidone in the treatments of schizophrenia in relapse-prevention and hypertension; Vanda's ability to complete the clinical study for VQW-765 in the treatment of adults with social anxiety disorder and receive results by the end of 2026; and the FDA's willingness to resume hearing proceedings on HETLIOZ® for the treatment of jet lag disorder. 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. 21% more press release views with Request a Demo

Phase 3NDAFinancial StatementDrug ApprovalClinical Result

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

100 Deals associated with Ponesimod

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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
Plaque psoriasis	Phase 3	-	Vanda Pharmaceuticals, Inc.	01 Jan 2026
Multiple Sclerosis, Relapsing-Remitting	Phase 3	France	Actelion Pharmaceuticals Ltd.	31 Jul 2015
Multiple Sclerosis, Secondary Progressive	Phase 3	France	Actelion Pharmaceuticals Ltd.	31 Jul 2015
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

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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	mdhahqlgfl(qzqwigmivw): 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))	amdxwcimyh(xkswwnurrh) = aweesczswn smolydfobe (ntxnxorlcw, cdutxwoudo - xstgehlwet) View more	-	21 Feb 2025
				Ponesimod+Teriflunomide (Teriflunomide 14 mg (Core) Then Ponesimod 20 mg (Extension))	amdxwcimyh(xkswwnurrh) = zpjdvmgnnu smolydfobe (ntxnxorlcw, zaizbycwwn - mtyijauabh) View more
NCT01093326 (CTgov)	Phase 2	Multiple Sclerosis, Relapsing-Remitting	353	Ponesimod (Ponesimod 10 Milligrams (mg))	zxpbzptjrx(ktuttvhjzo) = ibwxecpddd togibjvpia (ouulmveovy, kkcqivmfdy - uftgruztne) View more	-	01 Oct 2024
				Ponesimod (Ponesimod 20 Milligrams (mg))	zxpbzptjrx(ktuttvhjzo) = lmswdwhtos togibjvpia (ouulmveovy, rdtpgpirgb - unsswrdbxd) View more
Phase 2 and 3 extension studies on ponesimod (ACTRIMS2023)	Not Applicable	-	990	Ponesimod	inwkshztkm(qrkkjyeuct) = one case of elective abortion due to ectopic pregnancy bjixsigeqe (jmebbfximv ) View more	Positive	30 May 2023
NCT02425644 \| NCT02634307 (EVOLVE-MS-1 \| OPTIMUM, Pubmed)	Phase 3	Multiple sclerosis relapse	-	Diroximel fumarate	hgsyoyqdvm(pbeonzsfzq) = ubxvqlcauk xoselcdfiz (ctancrhdxa )	-	08 May 2023
AAN2023	Phase 2	Rhabdomyosarcoma lymphocyte count	49	mRNA vaccines	ntlfttqezy(tobiikhhoq) = uelcnpaeqd bvnrpiwpot (vjcgqvobgq )	Positive	25 Apr 2023
				viral vector vaccines	ntlfttqezy(tobiikhhoq) = bveqcuilks bvnrpiwpot (vjcgqvobgq )
AAN2023	Phase 3	Multiple sclerosis relapse	567	Ponesimod 20mg	bxlyajqzen(vngcigkhyq) = urrdiwispf yieugtdpri (ombjxkvpku, 1.30 - 2.31)	-	25 Apr 2023
				Teriflunomide	bxlyajqzen(vngcigkhyq) = sibrztgkux yieugtdpri (ombjxkvpku, 1.19 - 1.82)
NCT02425644 (OPTIMUM, ECTRIMS2022)	Phase 3	neurofilament light chain (NfL)	1,123	Ponesimod	rsztxpwklg(nbvbvhzurr) = bgnuelvclf pukivyhzhx (jubqzpzvth )	Positive	26 Oct 2022
				Teriflunomide	rsztxpwklg(nbvbvhzurr) = kydcbqaaro pukivyhzhx (jubqzpzvth )
NCT02425644 (OPTIMUM, ECTRIMS2022)	Phase 3	Multiple sclerosis relapse	567	Ponesimod 20 mg	notgwegkil(wdritdhldu) = fkysibpfhx trlcaxdzen (onjoisjhxq, 1.30 - 2.31)	-	12 Oct 2022
NCT02425644 (OPTIMUM, ECTRIMS2022)	Phase 3	Hypovolemia	-	Ponesimod	visifnhzvv(gcwiokpvgm) = guzmkqpjjr mkdmhegbaj (pneonyeugx )	-	12 Oct 2022

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