Drugs of today
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Venetoclax (ABT-199) is a small-molecule selective oral inhibitor of the antiapoptotic protein Bcl-2 that promotes programmed cell death of chronic lymphocytic leukemia (CLL) cells regulating the release of proapoptotic factors, such as Smac/Diablo, apoptosis-inducing factor (AIF) and cytochrome c. In April 2016, the U. ⋯ Food and Drug Administration (FDA) granted accelerated approval to venetoclax for patients diagnosed with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. This review will focus on the mechanism of action, preclinical studies and clinical development of venetoclax both as a monotherapy and in combination with other drugs for CLL in the current milieu of therapy dominated by novel tyrosine kinase inhibitors such as ibrutinib and idelalisib.
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Epilepsy is one of the most common chronic disorders of the brain affecting around 70 million people worldwide. Treatment is mainly symptomatic, and most patients achieve long-term seizure control. Up to one-third of the affected subjects, however, are resistant to anticonvulsant therapy. ⋯ Cannabidiol (CBD) is the first in a new class of antiepileptic drugs. It is a major chemical of the cannabis plant, which has antiseizure properties in absence of psychoactive effects. This article provides a critical review of the pharmacology of CBD and the most recent clinical studies that evaluated its efficacy and safety as adjunctive treatment of seizures associated with LGS and DS.
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Patients with metastatic triple-negative breast cancer (mTNBC) that has progressed on first-line therapy have a poor prognosis with limited therapeutic options. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate (ADC) that has shown promising efficacy in mTNBC. SG is comprised of SN-38, the active metabolite of irinotecan, conjugated via a hydrolyzable linker to the humanized RS7 antibody targeting trophoblast cell surface antigen 2 (Trop-2), a glycoprotein that is expressed at high levels in many epithelial solid tumors. ⋯ S. Food and Drug Administration (FDA) for the treatment of patients with pretreated mTNBC. In this review, we summarize available data regarding the pharmacology, pharmacokinetics, safety and efficacy of SG and describe ongoing and future clinical studies investigating this agent.
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Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and multiorgan failure, resulting from autoantibody-mediated severe A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) deficiency. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk of exacerbations, refractoriness and death. Caplacizumab (Cablivi; Ablynx, a Sanofi company), a nanobody targeting von Willebrand factor (vWF), has been recently approved in the E. ⋯ We detail here the preclinical and clinical data on caplacizumab for iTTP, including the recent studies that led to approval by the U. S. Food and Drug Administration (FDA) in 2019.
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On August 30, 2017, the U. S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). ⋯ Results from clinical trials indicate that anti-CD19 CAR T-cell therapies could successfully induce high response rates in B-ALL patients. However, related toxicities, such as cytokine release syndrome and CAR T-cell-related encephalopathy syndrome, may be severe or even fatal, and the management of such toxicities is therefore vital. This review will focus on the clinical application of anti-CD19 CAR T-cell therapy in B-ALL treatment, including design features of CAR constructs, therapeutic use of tisagenlecleucel, CAR T-cell therapy clinical trials and related toxicity, and prospects for cancer immunotherapy.