Drugs of today最新文献

Mitapivat for sickle cell disease and thalassemia. Mitapivat治疗镰状细胞病和地中海贫血。

IF 1.8 4区医学

Drugs of today Pub Date : 2023-03-01 DOI: 10.1358/dot.2023.59.3.3521880

Federica Pilo, Emanuele Angelucci

{"title":"Mitapivat for sickle cell disease and thalassemia.","authors":"Federica Pilo, Emanuele Angelucci","doi":"10.1358/dot.2023.59.3.3521880","DOIUrl":"10.1358/dot.2023.59.3.3521880","url":null,"abstract":"Mitapivat, an oral first-in-class activator of erythrocyte pyruvate kinase (PKR), was first investigated in patients with pyruvate kinase deficiency (PKD), where it was found to improve hemoglobin (Hb) concentrations in patients who did not regularly receive transfusions and to reduce transfusion burden in patients who receive regular transfusions. It was approved in 2022 for the treatment of PKD and is being explored in other hereditary chronic conditions that are associated with hemolytic mechanisms of anemia, such as sickle cell disease (SCD) and thalassemia. In a proof-of-concept phase I study in SCD, treatment with mitapivat demonstrated efficacy in increasing Hb concentrations, but also restored the thermostability of PKR, increasing its activity and decreasing 2,3-diphosphoglycerate (2,3-DPG) levels in sickle erythrocytes, which decreases Hb polymerization by increasing the affinity of Hb to oxygen. In thalassemia, mitapivat is hypothesized to increase adenosine triphosphate (ATP) production and mitigate harmful effects on red blood cells. This hypothesis is supported by preclinical data showing that mitapivat ameliorated ineffective erythropoiesis, iron overload and anemia in the Hbbth3/+ murine model of β-thalassemia intermedia. The efficacy and safety of mitapivat were confirmed in an open-label, multicenter, phase II study of patients with non-transfusion-dependent α-thalassemia or β-thalassemia, where activation of PKR improves anemia, and the drug showed a tolerable safety profile comparable to that in previous studies in other hemolytic anemias. Together, these efficacy and safety results provide rationale for continuing investigation of mitapivat for the treatment of thalassemia and SCD, developing other PK activators and starting investigational studies in other acquired diseases characterized by dyserythropoiesis and hemolytic anemia.","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10804564","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}

引用次数: 0

Secukinumab, ixekizumab, bimekizumab and brodalumab for psoriasis and psoriatic arthritis. 用于银屑病和银屑病关节炎的Secukinumab, ixekizumab, bimekizumab和brodalumab。

IF 1.8 4区医学

Drugs of today Pub Date : 2023-03-01 DOI: 10.1358/dot.2023.59.3.3419557

Theodora Simopoulou, Sotirios G Tsiogkas, Efterpi Zafiriou, Dimitrios P Bogdanos

引用次数: 1

Anakinra as a potential treatment for COVID-19. 阿那白作为COVID-19的潜在治疗方法。

IF 1.8 4区医学

Drugs of today Pub Date : 2023-03-01 DOI: 10.1358/dot.2023.59.3.3542446

Matthew W McCarthy

引用次数: 1

Cenegermin for the treatment of dry eye disease. 用于治疗干眼症。

IF 1.8 4区医学

Drugs of today Pub Date : 2023-03-01 DOI: 10.1358/dot.2023.59.3.3521858

Giulia Coco, Giulia Piccotti, Vito Romano, Lorenzo Ferro Desideri, Aldo Vagge, Carlo Enrico Traverso, Marco Pellegrini, Alice Bruscolini, Marco Marenco, Giuseppe Giannaccare

{"title":"Cenegermin for the treatment of dry eye disease.","authors":"Giulia Coco, Giulia Piccotti, Vito Romano, Lorenzo Ferro Desideri, Aldo Vagge, Carlo Enrico Traverso, Marco Pellegrini, Alice Bruscolini, Marco Marenco, Giuseppe Giannaccare","doi":"10.1358/dot.2023.59.3.3521858","DOIUrl":"https://doi.org/10.1358/dot.2023.59.3.3521858","url":null,"abstract":"Dry eye disease (DED) is the most common ocular surface disorder affecting millions of people worldwide. Due to its chronic nature, the management of DED still represents a challenge in the ophthalmic practice. Nerve growth factor (NGF), which is expressed along with its high-affinity TrkA receptor on the ocular surface complex, has been widely studied for the treatment of neurotrophic keratopathy, and a novel recombinant human NGF (rhNGF) has recently received full market authorization in this setting. Since NGF has shown in both in vitro and in vivo studies to promote corneal healing, to enhance conjunctival epithelium differentiation and mucin secretion, and to stimulate tear film production and functionality, it could provide potential benefits also in patients with DED. A recent phase II clinical trial has assessed the role of rhNGF in DED patients, demonstrating significant improvements of DED signs and symptoms after 4 weeks of treatment. Further clinical evidence will be provided by the 2 ongoing phase III clinical trials. This review aims at comprehensively illustrating the rationale of use along with the efficacy and safety profile of topical NGF in patients with DED.","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10828648","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}

引用次数: 2

Sugemalimab, a novel PD-L1 inhibitor for treatment of advanced or metastatic non-small cell lung cancer. Sugemalimab，一种用于治疗晚期或转移性非小细胞肺癌的新型PD-L1抑制剂。

IF 1.8 4区医学

Drugs of today Pub Date : 2023-03-01 DOI: 10.1358/dot.2023.59.3.3507759

Mandy Sakamoto, Antonio Jimeno

引用次数: 1

Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma. Tebentafusp:一种治疗转移性葡萄膜黑色素瘤的新药。

IF 1.8 4区医学

Drugs of today Pub Date : 2023-03-01 DOI: 10.1358/dot.2023.59.3.3542417

Zhijian Wang, Yuhao Xie, Jing-Quan Wang, Yuanhui Cheng, Joshua Fleishman, Zhe-Sheng Chen, Yun Chen

{"title":"Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma.","authors":"Zhijian Wang, Yuhao Xie, Jing-Quan Wang, Yuanhui Cheng, Joshua Fleishman, Zhe-Sheng Chen, Yun Chen","doi":"10.1358/dot.2023.59.3.3542417","DOIUrl":"https://doi.org/10.1358/dot.2023.59.3.3542417","url":null,"abstract":"On January 25, 2022, the U.S. Food and Drug Administration (FDA) approved the use of tebentafusp, a bispecific glycoprotein 100 (gp100) peptide-human leukocyte antigen (HLA)-directed CD3 T-cell activator, for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Pharmacodynamic data indicate that tebentafusp targets a specific HLA-A*02:01/gp100 complex, activating both CD4+/CD8+ effector and memory T cells that induce tumor cell death. Tebentafusp is administered to patients via intravenous infusion daily or weekly, depending on the indication. Phase III trials have documented a 1-year overall survival of 73%, overall response rate of 9%, progression-free survival of 31% and disease control rate of 46%. Common adverse events reported are cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache and vomiting. Compared to other types of melanomas, mUM presents with a distinct profile of genetic mutations, which phenotypically results in limited survival efficacy when using traditional melanoma treatments. The low current treatment efficacy for mUM, alongside a poor long-term prognosis and high mortality rates, gives precedence for the approval of tebentafusp to be groundbreaking in its clinical impact. This review will discuss the pharmacodynamic and pharmacokinetic profile, and the clinical trials used to evaluate the safety and efficacy of tebentafusp.","PeriodicalId":11397,"journal":{"name":"Drugs of today","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10804563","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}

引用次数: 2

Monoclonal antibodies for treatment of osteoporosis. 治疗骨质疏松症的单克隆抗体。

IF 1.8 4区医学

Drugs of today Pub Date : 2023-03-01 DOI: 10.1358/dot.2023.59.3.3453905

Kveta Kroupova, Vladimir Palicka, Jan Rosa

引用次数: 1

Clascoterone for treatment of acne. 治疗痤疮。

IF 1.8 4区医学

Drugs of today Pub Date : 2023-02-01 DOI: 10.1358/dot.2023.59.2.3507749

Cyriac Manjaly, Jeremy Martinez, John Barbieri, Arash Mostaghimi

引用次数: 0

Atidarsagene autotemcel for metachromatic leukodystrophy. 异色差性脑白质营养不良的Atidarsagene自体细胞。

IF 1.8 4区医学

Drugs of today Pub Date : 2023-02-01 DOI: 10.1358/dot.2023.59.2.3461911

Martina Messina, Paul Gissen

{"title":"Atidarsagene autotemcel for metachromatic leukodystrophy.","authors":"Martina Messina, Paul Gissen","doi":"10.1358/dot.2023.59.2.3461911","DOIUrl":"https://doi.org/10.1358/dot.2023.59.2.3461911","url":null,"abstract":"Metachromatic leukodystrophy (MLD) is a rare autosomal recessive disorder of sphingolipid metabolism, due to a deficiency of the enzyme arylsulfatase A (ARSA). The main clinical signs of the disease are secondary to central and peripheral nervous system demyelination. MLD is subdivided into early- and late-onset subtypes based upon the onset of neurological disease. The early-onset subtype is associated with a more rapid progression of the disease that leads to death within the first decade of life. Until recently, no effective treatment was available for MLD. The blood-brain barrier (BBB) prevents systemically administered enzyme replacement therapy from reaching target cells in MLD. The evidence for the efficacy of hematopoietic stem cell transplantation is limited to the late-onset MLD subtype. Here, we review the preclinical and clinical studies that facilitated the approval of the ex vivo gene therapy atidarsagene autotemcel for early-onset MLD by the European Medicines Agency (EMA) in December 2020. This approach was studied in an animal model first and then in a clinical trial, eventually proving its efficacy in preventing disease manifestations in presymptomatic patients and stabilizing its progression in paucisymptomatic subjects. This new therapeutic consists of patients' CD34+ hematopoietic stem/progenitor cells (HSPCs) transduced with a lentiviral vector encoding functional ARSA cDNA. The gene-corrected cells get reinfused into the patients after a cycle of chemotherapy conditioning.","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":"9327735","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}

引用次数: 0

Donafenib in hepatocellular carcinoma. 多纳非尼在肝细胞癌中的作用。

IF 1.8 4区医学

Drugs of today Pub Date : 2023-02-01 DOI: 10.1358/dot.2023.59.2.3507751

Rusi Chen, Luca Ielasi, Alma di Carlo, Francesco Tovoli

引用次数: 2