- |||||||||| Zeposia (ozanimod) / BMS
Review, Journal: The discovery and development of the sphingosine 1-phosphate receptor modulator ozanimod in ulcerative colitis. (Pubmed Central) - Nov 16, 2024 In this review, the discovery and development of the first approved S1P modulator, ozanimod, is described in detail: from design of initial screens to discover unique binding agents, to extensive chemical modifications to improve pharmacokinetic and safety profiles, and through preclinical and clinical studies validating mechanism and establishing safety and efficacy. Ultimately, this review will not only inform the reader of the unique path to development of a clinical S1P modulator for UC, but will also highlight advances made and gaps remaining to individualize therapeutic approaches for inflammatory bowel disease.
- |||||||||| Review, Journal: Interpreting modern randomized controlled trials of medical therapy in inflammatory bowel disease. (Pubmed Central) - Oct 26, 2024
Importantly, the methodology of RCTs in IBD has evolved substantially, with new trial designs, evaluation of unique patient populations, and different types of efficacy and safety end points being key innovations. In this Review, we provide a comprehensive evaluation of how modern RCTs of IBD medical therapies have evolved and the implications for their appraisal that will help guide the application of these data to clinical practice.
- |||||||||| Zyclara (imiquimod) / Mochida, Viatris, Bausch Health
Journal: Sphingosine 1-phosphate receptor 2 in keratinocytes plays a key role in reducing inflammation in psoriasis. (Pubmed Central) - Oct 11, 2024 Spatial transcriptomics, RT-qPCR, and flow cytometry were used to map the immune cell landscape and its association with metabolic pathways in an imiquimod (IMQ)-induced psoriasis-like inflammation in S1pr2fl/fl K14-Cre mice that could not sense sphingosine-1-phosphate (S1P) in the epidermis through the S1PR2 receptor...Other S1PR modulators did not improve the worsening of psoriasis-like inflammation caused by S1PR2 deficiency in keratinocytes. This study reaches two main signals from keratinocytes play a central role in creating an immune environment that promotes the development of psoriasis, and stimulating S1PR2, instead of suppressing it, represents a potential therapeutic approach for psoriasis.
- |||||||||| Zeposia (ozanimod) / BMS, Velsipity (etrasimod) / Pfizer, VTX002 / Ventyx Biosci
PK/PD data, Review, Journal: Pharmacokinetics of S1P receptor modulators in the treatment of ulcerative colitis. (Pubmed Central) - Sep 25, 2024 Due to its pharmacokinetic features, this class of drugs has certain advantages such as an oral administration, a short half-life, a high volume of distribution, and no immunogenicity. On the other hand, there are risks of cardiological and ophthalmological side-effects, as well as drug-drug interactions risk, that require special attention from the healthcare providers.
- |||||||||| Review, Journal: Translational characterization of immune pathways in inflammatory bowel disease: insights for targeted treatments. (Pubmed Central) - Sep 24, 2024
The treatment landscape for IBD has rapidly expanded, particularly with the development of biologics targeting TNF-?, integrins, and S1P modulators, as well as newer agents such as IL-12/IL-23 inhibitors and JAK inhibitors, offering robust efficacy and safety profiles. However, challenges persist in understanding and effectively treating difficult-to-treat IBD, highlighting the need for continued research to uncover novel therapeutic targets and optimize patient outcomes.
- |||||||||| Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Review, Journal: Riesgo de c (Pubmed Central) - Sep 3, 2024 Sphingosine-1-phosphate receptor modulators, such as fingolimod and siponimod are associated with a higher risk of basal cell carcinoma (BCC), but not squamous cell carcinoma, or melanoma...Alemtuzumab and cladribine show isolated associations with skin cancer...Given the evidence currently available, it is of paramount importance to advocate for necessary dermatological assessments that should be individualized to the risk profile of each patient. Nonetheless, additional prospective studies are still needed to establish efficient dermatological follow-up protocols.
- |||||||||| Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
Review, Journal: Risk of skin cancer associated with disease-modifying therapies in multiple sclerosis: a modern comprehensive evidence review. (Pubmed Central) - Sep 3, 2024 Sphingosine-1-phosphate receptor modulators, such as fingolimod and siponimod are associated with a higher risk of basal cell carcinoma (BCC), but not squamous cell carcinoma, or melanoma...Alemtuzumab and cladribine show isolated associations with skin cancer...Given the evidence currently available, it is of paramount importance to advocate for necessary dermatological assessments that should be individualized to the risk profile of each patient. Nonetheless, additional prospective studies are still needed to establish efficient dermatological follow-up protocols.
- |||||||||| Review, Journal: Small Molecule Therapy for Inflammatory Bowel Disease: JAK Inhibitors and S1PR Modulators (Pubmed Central) - Aug 23, 2024
Ozanimod and etrasimod are S1PRMs approved for the treatment of UC, but they can cause side effects such as bradycardia, conduction disorder, and macular edema. Overall, JAK inhibitors and S1PRMs offer significant benefits in managing IBD, although their potential side effects require careful monitoring.
- |||||||||| fingolimod / Generic mfg.
EAE model of multiple sclerosis: prophylactic versus treatment fingolimod (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_368; This study reports that the EAE mouse model can effectively mimic MS symptoms and the temporally-dependent start of a daily dose of Fin can prevent disease onset, development of axonal damage, neuroinflammation and inflammatory cell infiltration in the spinal cord. Therefore, it could be a useful approach to studying treatments that may modify these processes and compare their efficacy with Fin
- |||||||||| Velsipity (etrasimod) / Pfizer
Low Incidence of Macular Edema in Patients in the Etrasimod Clinical Program (Exhibit Hall E) - Aug 20, 2024 - Abstract #ACG2024ACG_1353; In the Placebo-controlled UC cohort, Macular edema was reported in two patients (0.3%; IR 0.70) receiving etrasimod 2 mg QD (one patient with long-term corticosteroid use in ELEVATE UC 52 and one patient with prior uveitis in ELEVATE UC 12, which was not considered clinically significant by the investigator) and one patient (0.3%; IR 0.84) receiving placebo (ELEVATE UC 12). In the All UC cohort, one patient (0.1%; IR 0.13) receiving etrasimod 2 mg QD during the ELEVATE UC OLE reported two events of Cystoid macular edema (Table).
- |||||||||| obefazimod (ABX464) / Abivax
Trial primary completion date: ABX464-107: ABTECT - Maintenance (clinicaltrials.gov) - Aug 7, 2024 P3, N=1050, Recruiting, Clinicaltrials.gov: NCT03945188; NCT03996369. Trial primary completion date: Dec 2029 --> Jan 2026
- |||||||||| obefazimod (ABX464) / Abivax
Trial completion date, Trial primary completion date: ABX464-107: ABTECT - Maintenance (clinicaltrials.gov) - Aug 1, 2024 P3, N=1050, Recruiting, Continuous monitoring of their long-term safety is necessary. Trial completion date: Jun 2026 --> Jan 2030 | Trial primary completion date: Jan 2026 --> Dec 2029
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