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Clinical data | |
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Trade names | Ponvory |
Other names | ACT-128800 |
AHFS/Drugs.com | Micromedex Detailed Consumer Information |
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Routes of administration | By mouth |
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Pharmacokinetic data | |
Metabolism | 2 main metabolites |
Elimination half-life | 31–34 hrs [7] |
Excretion | Feces (57–80%, 26% unchanged), urine (10–18%) [8] |
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Chemical and physical data | |
Formula | C23H25ClN2O4S |
Molar mass | 460.97 g·mol−1 |
3D model (JSmol) | |
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Ponesimod, sold under the brand name Ponvory, is a medication for the treatment of multiple sclerosis. [4] [9] It is a sphingosine-1-phosphate receptor modulator. [4]
The most common side effects include upper respiratory tract infection, hepatic transaminase elevation, and hypertension. [4] [5] [9]
Ponesimod was approved for medical use in the United States in March 2021, [4] [9] and in the European Union in June 2021. [10]
Ponesimod is indicated for the treatment of relapsing forms of multiple sclerosis including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. [4] [5]
Common adverse effects in studies were temporary bradycardia (slow heartbeat), usually at the beginning of the treatment, dyspnoea (breathing difficulties), and increased liver enzymes (without symptoms). No significant increase of infections was observed under ponesimod therapy. [11] QT prolongation is detectable but was considered to be too low to be of clinical importance in a study. [12]
Like fingolimod, which is already approved for the treatment of multiple sclerosis, ponesimod blocks the sphingosine-1-phosphate receptor. This mechanism prevents lymphocytes (a type of white blood cells) from leaving lymph nodes. [11] Ponesimod is selective for subtype 1 of this receptor, S1P1. [13]
In a 2009–2011 Phase II clinical trial including 464 multiple sclerosis patients, ponesimod treatment resulted in fewer new active brain lesions than placebo, measured during the course of 24 weeks. [11] [14]
In a 2010–2012 Phase II clinical trial including 326 patients with psoriasis, 46 or 48% of patients (depending on dosage) had a reduction of at least 75% Psoriasis Area and Severity Index (PASI) score compared to placebo in 16 weeks. [11] [15] The approval is already applied for in 2020. [16]
In a 2015–2019 Phase III randomised, double-blind clinical trial of 1133 adult patients with relapsing multiple sclerosis, those under ponesimod treatment showed a 30% reduction in annual relapse rate and a significantly reduced number of new inflammatory lesions on brain MRI by 56% compared to those taking teriflunomide. [17]
In October 2020, Janseen-Cilag International NV submitted an application for the modification of agreed pediatric investigation plan (PIP) to European Medicines Agency (including deferral and waiver criteria). This application was launched for the amendments of proposed changes against the European Medicines Agency’s decisions issued in November 2012 and April 2018. The approved procedure has already started in December 2022. To evaluate pharmacodynamics and pharmacokinetics efficacy of ponesimod in pediatric patients with relapsing-remitting multiple sclerosis (RRMS); a multicenter, randomized, double blind clinical study of duration of 108 weeks treatment for age group 10 to less than 18 years, is in progress. The clinical trial will end in November 2027. [18] [19]
In March 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Ponvory, intended for the treatment of active relapsing forms of multiple sclerosis. [20] The applicant for this medicinal product is Janssen-Cilag International N.V. [20] Ponesimod was approved for medical use in the European Union in May 2021. [5]
Daclizumab is a therapeutic humanized monoclonal antibody which was used for the treatment of adults with relapsing forms of multiple sclerosis (MS). Daclizumab works by binding to CD25, the alpha subunit of the IL-2 receptor of T-cells.
Fingolimod, sold under the brand name Gilenya, is an immunomodulating medication, used for the treatment of multiple sclerosis. Fingolimod is a sphingosine-1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction. It has been reported to reduce the rate of relapses in relapsing-remitting multiple sclerosis by approximately one-half over a two-year period.
Natalizumab, sold under the brand name Tysabri among others, is a medication used to treat multiple sclerosis and Crohn's disease. It is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin. It is given by intravenous infusion. The drug is believed to work by reducing the ability of inflammatory immune cells to attach to and pass through the cell layers lining the intestines and blood–brain barrier.
Ustekinumab, sold under the brand name Stelara among others, is a monoclonal antibody medication developed by Janssen Pharmaceuticals, for the treatment of Crohn's disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis, targeting both IL-12 and IL-23.
Ofatumumab is a fully human monoclonal antibody to CD20, which appears to provide rapid B-cell depletion. Under the brand name Kesimpta, it is approved for the treatment of multiple sclerosis in the United States as well as in the European Union and other regions. Under the brand name Arzerra, it is approved for the treatment of certain types of chronic lymphocytic leukemia (CLL) in the United States. It is sold by Novartis under license from Genmab.
Dimethyl fumarate (DMF) is the methyl ester of fumaric acid and is named after the earth smoke plant. Dimethyl fumarate combined with three other fumaric acid esters (FAEs) is solely licensed in Germany as an oral therapy for psoriasis. Since 2013, it has been approved by the U.S. Food and Drug Administration (FDA) as a treatment option for adults with relapsing multiple sclerosis. In 2017, an oral formulation of dimethyl fumarate was approved for medical use in the European Union as a treatment for moderate-to-severe plaque psoriasis. Dimethyl fumarate is thought to have immunomodulatory properties without causing significant immunosuppression.
Teriflunomide, sold under the brand name Aubagio, is the active metabolite of leflunomide. Teriflunomide was investigated in the Phase III clinical trial TEMSO as a medication for multiple sclerosis (MS). The study was completed in July 2010. 2-year results were positive. However, the subsequent TENERE head-to-head comparison trial reported that "although permanent discontinuations [of therapy] were substantially less common among MS patients who received teriflunomide compared with interferon beta-1a, relapses were more common with teriflunomide." The drug was approved for use in the United States in September 2012 and for use in the European Union in August 2013.
Atacicept is a recombinant fusion protein designed to inhibit B cells, thereby suppressing autoimmune disease. The designer protein combines the binding site for two cytokines that regulate maturation, function, and survival of B cells - B-lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL), with the constant region of immunoglobin. Atacicept blocks activation of B cells by the tumor necrosis factor receptor superfamily member 13B, a transmembrane receptor protein found predominantly on the surface of B cells. Like the monoclonal antibody belimumab, atacicept blocks the binding of BLyS, but it also blocks APRIL. Binding of these TACI ligands induces proliferation, activation, and longevity of B cells and thus their production of autoantibodies. Atacicept is thought to selectively impair mature B cells and plasma cells with less impact on progenitor cells and memory B cells.
Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular course juvenile idiopathic arthritis, and ulcerative colitis. It is a janus kinase (JAK) inhibitor, discovered and developed by the National Institutes of Health and Pfizer.
Ublituximab, sold under the brand name Briumvi, is an immunomodulator used for the treatment of multiple sclerosis. It is a CD20-directed cytolytic monoclonal antibody.
Voclosporin, sold under the brand name Lupkynis, is a calcineurin inhibitor used as an immunosuppressant medication for the treatment of lupus nephritis. It is an analog of ciclosporin that has enhanced action against calcineurin and greater metabolic stability.
Anifrolumab, sold under the brand name Saphnelo, is a monoclonal antibody used for the treatment of systemic lupus erythematosus. It binds to the type I interferon receptor, blocking the activity of type I interferons such as interferon-α and interferon-β.
Lemborexant, sold under the brand name Dayvigo, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance in adults. The medication is taken by mouth.
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Ozanimod, sold under the brand name Zeposia, is an immunomodulatory medication for the treatment of relapsing multiple sclerosis and ulcerative colitis. It acts as a sphingosine-1-phosphate receptor (S1PR) agonist, sequestering lymphocytes to peripheral lymphoid organs and away from their sites of chronic inflammation.
Siponimod, sold under the brand name Mayzent, is a selective sphingosine-1-phosphate receptor modulator for oral use that is used for multiple sclerosis (MS). It is intended for once-daily oral administration.
Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.
Diroximel fumarate, sold under the brand name Vumerity, is a medication used for the treatment of relapsing forms of multiple sclerosis (MS). It acts as an immunosuppressant and anti-inflammatory drug. Its most common adverse effects are flushing and gastrointestinal problems.
Ciltacabtagene autoleucel, sold under the brand name Carvykti, is an anti-cancer medication used to treat multiple myeloma. Ciltacabtagene autoleucel is a BCMA -directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using the recipient's own T-cells, which are collected and genetically modified, and infused back into the recipient.
Spesolimab, sold under the brand name Spevigo, is a monoclonal antibody used for the treatment of generalized pustular psoriasis (GPP). It is an interleukin-36 receptor (IL-36R) antagonist. It is given via injection into a vein.