Drugs of today最新文献

{"title":"Nivolumab and relatlimab for the treatment of melanoma.","authors":"Xuan-Yu Chen,&nbsp;Yi-Dong Li,&nbsp;Yuhao Xie,&nbsp;Lu-Qi Cao,&nbsp;Charles R Ashby,&nbsp;Hongbing Zhao,&nbsp;Zhe-Sheng Chen","doi":"10.1358/dot.2023.59.2.3509756","DOIUrl":"https://doi.org/10.1358/dot.2023.59.2.3509756","url":null,"abstract":"<p><p>Melanoma is a highly lethal type of skin cancer. Although an early diagnosis, in combination with surgery for nonmetastatic melanomas, significantly increases the probability of survival, there are no efficacious treatments for metastatic melanoma. Nivolumab and relatlimab are monoclonal antibodies that selectively interact with and block the proteins programmed cell death protein 1 (PD-1) and lymphocyte activation protein 3 (LAG-3), respectively, and thus, their activation by their cognate ligands. The combination of these immunotherapy drugs was approved in 2022 by the United States Food and Drug Administration (FDA) for the treatment of melanoma. Data from clinical trials indicated that, compared to nivolumab monotherapy, nivolumab and relatlimab produced more than a 2-fold median increase in progression-free survival (PFS) and a higher response rate in melanoma patients. This is an important finding as the response of patients to immunotherapies is limited due to dose-limiting toxicities and secondary drug resistance. This review article will discuss the pathogenesis of melanoma and the pharmacology of nivolumab and relatlimab. In addition, we will provide i) a summary of the anticancer drugs that inhibit LAG-3 and PD-1 in cancer patients and ii) our perspective about the use of nivolumab in combination with relatlimab to treat melanoma.</p>","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9327737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anifrolumab in systemic lupus erythematosus.","authors":"Michael F Loncharich,&nbsp;Ian Robertson","doi":"10.1358/dot.2023.59.2.3521876","DOIUrl":"https://doi.org/10.1358/dot.2023.59.2.3521876","url":null,"abstract":"<p><p>Systemic lupus erythematosus is a complex autoimmune disease with variable disease presentation and progression. Hydroxychloroquine and corticosteroids are first-line therapies. Disease severity and organ system involvement guide escalation of immunomodulatory medications beyond these mainstays. Anifrolumab is a first-in-class global type 1 interferon inhibitor recently approved by the United States Food and Drug Administration (FDA) for systemic lupus erythematosus in addition to standard of care. This article reviews the role of type 1 interferons in lupus pathophysiology and the evidence leading to anifrolumab's approval with particular emphasis on the MUSE, TULIP-1 and TULIP-2 trials. In addition to standard of care, anifrolumab can reduce corticosteroid requirements and reduce lupus disease activity, especially skin and musculoskeletal manifestations, with an acceptable safety profile.</p>","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10765443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ciltacabtagene autoleucel for the treatment of multiple myeloma.","authors":"Sarah A Holstein","doi":"10.1358/dot.2023.59.1.3509751","DOIUrl":"https://doi.org/10.1358/dot.2023.59.1.3509751","url":null,"abstract":"<p><p>While treatment options for multiple myeloma (MM) are continuing to expand, this disease remains one characterized by requiring multiple lines of therapy, with generally decreasing effectiveness of each subsequent line. The development of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy has proven an exception to this rule. In the trial that led to approval of the BCMA CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel) by the U.S. Food and Drug Administration (FDA), deep and durable response rates were observed in heavily pretreated patients. In this review we summarize the available clinical trial data for cilta-cel, including discussion on notable adverse events, as well as discuss ongoing studies that are likely to lead to paradigm changes in the management of MM. In addition, we discuss the issues that currently surround the real-world utilization of cilta-cel.</p>","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9327739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lutetium Lu 177 vipivotide tetraxetan for prostate cancer.","authors":"Xing Liu,&nbsp;Gao-Chuan Fang,&nbsp;Hao Lu,&nbsp;Zhen-Duo Shi,&nbsp;Zhe-Sheng Chen,&nbsp;Cong-Hui Han","doi":"10.1358/dot.2023.59.1.3476574","DOIUrl":"https://doi.org/10.1358/dot.2023.59.1.3476574","url":null,"abstract":"<p><p>On March 23, 2022, the U.S. Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan), also known as 177Lu-PSMA-617, for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who have highly expressed prostate-specific membrane antigen (PSMA) and have at least one metastatic lesion. It is the first FDA-approved targeted radioligand therapy for eligible men with PSMA-positive mCRPC. Lutetium Lu 177 vipivotide tetraxetan is a radioligand that strongly binds to PSMA, making it ideal for treating cancers of the prostate by targeted radiation, resulting in DNA damage and cell death. PSMA is overexpressed in cancer cells while being lowly expressed in normal tissues, which makes it an ideal theranostic target. As precision medicine advances, this is a thrilling turning point for highly individualized treatments. This review aims to summarize the pharmacology and clinical studies of the novel drug lutetium Lu 177 vipivotide tetraxetan for the treatment of mCRPC, emphasizing its mechanism of action, pharmacokinetics and safety.</p>","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9327736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 2022 TOPRA Annual Symposium - Medical Device and IVD Symposium (October 17-19, 2022 - Vienna, Austria).","authors":"Ana Mendez","doi":"10.1358/dot.2023.59.1.3521792","DOIUrl":"https://doi.org/10.1358/dot.2023.59.1.3521792","url":null,"abstract":"<p><p>The Organization for Professionals in Regulatory Affairs (TOPRA) celebrated its 2022 Annual Symposium, which took place in Vienna, Austria, from October 17 to 19, 2022, to discuss most relevant current issues and debate the future of healthcare regulatory affairs for medicinal products, medical devices/in vitro diagnostics (IVDs) and veterinary medicines.</p>","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10765444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Savolitinib for non-small cell lung cancer.","authors":"Magdalena Zaborowska-Szmi,&nbsp;Sebastian Szmit,&nbsp;Maciej Krzakowski,&nbsp;Dariusz M Kowalski","doi":"10.1358/dot.2023.59.1.3425324","DOIUrl":"https://doi.org/10.1358/dot.2023.59.1.3425324","url":null,"abstract":"<p><p>Savolitinib is a highly selective MET tyrosine kinase inhibitor. MET is involved in numerous cellular processes such as proliferation, differentiation and the formation of distant metastases. MET amplification and MET overexpression are quite common in many cancers, but MET exon 14 skipping alteration is most common in non-small cell lung cancer (NSCLC). The role of MET signaling as a bypass pathway in the development of acquired resistance to tyrosine kinase inhibitor (TKI) epidermal growth factor receptor (EGFR) therapy in cancer patients with EGFR gene mutation was documented. Potential beneficiaries of savolitinib therapy are patients with NSCLC and initial diagnosis of MET ex 14 skipping mutation. Savolitinib therapy can be effective in NSCLC patients with EGFR-mutant MET with progression during first-line treatment with an EGFR-TKI. Antitumor activity of savolitinib in combination with osimertinib is very promising as first-line therapy of patients with advanced EGFR-mutated NSCLC, initially with MET expression. The safety profile of savolitinib as monotherapy and in combination with osimertinib or gefitinib is so favorable in all available studies that this drug has become a very promising therapeutic option and is being intensively investigated in ongoing clinical trials.</p>","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10765445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pacritinib for myelofibrosis in adults with thrombocytopenia.","authors":"Dong-Hua Yang,&nbsp;Qisi Lu,&nbsp;Zhaohui Zhu,&nbsp;Guanghao Huang,&nbsp;Katherine Young","doi":"10.1358/dot.2022.58.12.3474538","DOIUrl":"https://doi.org/10.1358/dot.2022.58.12.3474538","url":null,"abstract":"<p><p>Myelofibrosis is a rare progressive cancer of the bone marrow that disrupts the normal production of healthy blood cells, leading to bone marrow failure. Patients with myelofibrosis and severe thrombocytopenia (platelet count below 50 × 10⁹/L) have a wide range of unmet medical needs compared with those without thrombocytopenia. Usually, these patients have an increased disease burden, increased transfusion dependence, shorter overall survival, and limited treatment options. Pacritinib is a new oral kinase inhibitor specifically targeting Janus kinase 2 (JAK2), interleukin-1 receptor-associated kinase 1 (IRAK-1) and colony-stimulating factor 1 receptor (CSF-1R), and is indicated for the treatment of adults with moderate or high risk of primary or secondary myelofibrosis (post-polycythemia or post-primary thrombocytopenia) whose platelet count is less than 50 × 10⁹/L. In this review, we introduce pacritinib and make a brief comparison of different JAK inhibitors in clinical application.</p>","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10607171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tezepelumab for asthma.","authors":"Santi Nolasco,&nbsp;Corrado Pelaia,&nbsp;Giulia Scioscia,&nbsp;Raffaele Campisi,&nbsp;Claudia Crimi","doi":"10.1358/dot.2022.58.12.3449205","DOIUrl":"https://doi.org/10.1358/dot.2022.58.12.3449205","url":null,"abstract":"The epithelium, once simply considered a protective barrier against harmful agents, has in recent times gained considerable relevance as an entity that can promote and regulate inflammatory processes through the production of cytokines, namely interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), known as \"alarmins\". TSLP, in particular, has been extensively studied as a possible therapeutic target in patients with severe asthma because it is involved in the inflammatory processes of both type 2-high and type 2-low inflammation. In this regard, tezepelumab (AMG-157/MEDI-9929), a TSLP-targeted first-in-class fully human monoclonal antibody, has been shown in phase II and III studies to be effective and safe in treating patients with severe asthma, regardless of the underlying endotype or phenotype and irrespective of baseline biomarkers, such as blood eosinophil count and fraction of exhaled nitric oxide. Here, we provide a comprehensive review of TSLP function in airway inflammatory processes, the clinical development of tezepelumab for severe asthma as well as its possible future indications.","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10607172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 vaccination in patients with multiple sclerosis receiving disease-modifying therapies: pragmatic issues.","authors":"Ioan-Alexandru Chirap-Mitulschi,&nbsp;Constantin Ghimus,&nbsp;Andreea Raluca Chirap-Mitulschi,&nbsp;Sabina Antonela Antoniu,&nbsp;Raluca Dragomir","doi":"10.1358/dot.2022.58.12.3455368","DOIUrl":"https://doi.org/10.1358/dot.2022.58.12.3455368","url":null,"abstract":"<p><p>The SARS-COV-2 pandemic has been a global public health problem since 2019, with over 400 million reported cases, 6 million deaths, and significant economic and social damage. Overlapping SARS-CoV-2 infection in patients with chronic diseases, such as multiple sclerosis (MS), causes management problems, especially in patients treated with disease-modifying therapies. Studies investigating COVID-19 vaccination effectiveness have shown variability in postvaccination immune response that depends on the patient's background treatment, and special attention is required for anti-CD20 therapies. Existing data on the efficacy of COVID-19 vaccination in patients with MS undergoing disease-modifying treatment are summarized and critically evaluated in this article.</p>","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10549323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cabotegravir: a novel HIV integrase inhibitor combined with rilpivirine as the first long-acting injectable program for the treatment of HIV infection.","authors":"John D Zeuli,&nbsp;Christina G Rivera,&nbsp;Bradley L Smith,&nbsp;Ashley Otto,&nbsp;Zelalem Temesgen","doi":"10.1358/dot.2022.58.12.3448340","DOIUrl":"https://doi.org/10.1358/dot.2022.58.12.3448340","url":null,"abstract":"<p><p>Cabotegravir, a novel HIV integrase inhibitor, shares structural similarity with dolutegravir and bictegravir. Its oral half-life is 32 hours, but cabotegravir nanosuspension for intramuscular injection yields half-lives ranging from 25 to 54 days, enabling extended interval dosing. Drug interactions are minimal, although oral doses require spacing from polyvalent cations, and potent uridine glucuronosyltransferase induction (e.g., rifampin, carbamazepine) requires avoidance due to anticipated subtherapeutic cabotegravir exposure through extended intervals. Randomized clinical trials combined cabotegravir treatment with rilpivirine to demonstrate treatment efficacy in patients living with HIV who had attained virologic suppression, lacked known/suspected mutations to either component, and had not experienced prior HIV treatment failure. Together, oral cabotegravir and rilpivirine maintained viral suppression in the LATTE study while the combination, given intramuscularly, performed comparably to conventional oral therapy in LATTE-2. FLAIR and ATLAS, respectively, demonstrated HIV suppression maintenance for monthly injections in treatment-naive participants and treatment-experienced patients, with ATLAS-2M supporting the efficacy of injections given every 2 months. Investigations to date show an excellent safety profile. Injectable cabotegravir causes short-lived, mild injection site reactions (primarily administration site pain/soreness) that decrease in frequency over time, produce attributable discontinuation rates of at least 2%, and generate satisfaction scores that favor injectable therapy over oral therapy. Virologic failure with resistance development is rare, primarily occurs in the first year of therapy, and is associated with baseline proviral DNA mutations to coadministered rilpivirine. A key component of the first U.S. Food and Drug Administration (FDA)-approved injectable maintenance treatment program for HIV, injectable cabotegravir heralds a new era in HIV treatment innovation. Here we provide a detailed review of the clinical pharmacology, administration and available formulations of the novel HIV integrase inhibitor cabotegravir with in-depth analysis of the clinical trial data, safety, satisfaction and viral resistance development when combined with rilpivirine as the first long-acting injectable program for the treatment of HIV infection.</p>","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10547925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}