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Severe post-partum hemorrhage (PPH) is a major cause of maternal mortality worldwide. Recombinant activated factor VII (rFVIIa) has recently been approved by the European Medicines Agency for the treatment of severe PPH if uterotonics fail to achieve hemostasis. Although large randomized controlled trials are lacking, accumulated evidence from smaller studies and international registries supports the efficacy of rFVIIa alongside extended standard treatment to control severe PPH. Because rFVIIa neither substitutes the activity of a missing coagulation factor nor bypasses a coagulation defect in this population, it is not immediately evident how it exerts its beneficial effect. Here, we discuss possible mechanistic explanations for the efficacy of rFVIIa and the published evidence in patients with severe PPH. Recombinant FVIIa may not primarily increase systemic thrombin generation, but may promote local thrombin generation through binding to activated platelets at the site of vascular wall injury. This explanation may also address safety concerns that have been raised over the administration of a procoagulant molecule in a background of increased thromboembolic risk due to both pregnancy-related hemostatic changes and the hemorrhagic state. However, the available safety data for this and other indications are reassuring and the rates of thromboembolic events do not appear to be increased in women with severe PPH treated with rFVIIa. We recommend that the administration of rFVIIa be considered before dilutional coagulopathy develops and used to support the current standard treatment in certain patients with severe PPH. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic metabolic disease affecting over 500 million people worldwide, which leads to severe complications and to millions of deaths yearly. When therapeutic goals are not reached with diet, physical activity, or non-insulin drugs, starting/adding insulin treatment is recommended by international guidelines. A novel recombinant insulin is icodec, a once-weekly insulin that successfully completed phase III trials and that has recently obtained the marketing authorization approval from the European Medicines Agency. This narrative review aims to assess icodec pharmacological and clinical features concerning evidence on benefit–risk profile, as compared to other basal insulins, addressing the potential impact on patients' unmet needs. Icodec is a full agonist, recombinant human insulin analogue characterized by an ultra-long half-life (196 h), enabling its use in once-weekly administration. Phase III randomized clinical trials involving more than 4000 diabetic patients, mostly type 2 DM, documented non-inferiority of icodec, as compared to currently available basal insulins, in terms of estimated mean reduction of glycated hemoglobin levels; a superiority of icodec, compared to control, was confirmed in insulin-naïve patients (ONWARDS 1, 3, and 5), and in patients previously treated with basal insulin (ONWARDS 2). Icodec safety profile was comparable to the currently available basal insulins. Once-weekly icodec has the potential to improve patients' adherence, thus positively influencing patients' treatment satisfaction as well as quality of life, especially in type 2 DM insulin-naïve patients. An improved adherence might positively influence glycemic target achievement, reduce overall healthcare costs and overcome some of the unmet patients' needs. Icodec has the potential to emerge as a landmark achievement in the evolution of insulin therapy, with a positive impact also for the National Health Services and the whole society. [ABSTRACT FROM AUTHOR]

B-cell acute lymphoblastic leukemia (B-ALL) is the most common subtype of acute leukemia in the pediatric population. The prognosis and treatment of B-ALL have dramatically improved over the past decade with the adoption of intensive and prolonged combination chemotherapy regimens. The advent of novel immunologic agents such as blinatumomab and inotuzumab has changed the treatment landscape of B-ALL. However, patients have continued to relapse, raising the need for novel therapies. Chimeric antigen receptor (CAR) T-cells have achieved a milestone in the treatment of B-ALL. Two CD19-targeting CAR T-cells were approved by the Food and Drug Administration and the European Medicines Agency for the treatment of relapsed and/or refractory B-ALL. In this review, we review the available data regarding CD19-targeting CAR T-cells with their safety profile as well as the mechanism of resistance to these agents and the way to overcome this resistance. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective and safe lipid-lowering treatments (LLT). The primary endpoint of the study was to assess the prevalence of patients eligible for treatment with PCSK9 inhibitors in a real-life clinical setting in Italy before and after the recent enlargement of reimbursement criteria. For this study, we consecutively considered the clinical record forms of 6231 outpatients consecutively admitted at the Lipid Clinic of the University Hospital of Bologna (Italy). Patients were stratified according to whether they were allowed or not allowed to access to treatment with PCSK9 inhibitors based on national prescription criteria and reimbursement rules issued by the Italian Medicines Agency (AIFA). According to the indications of the European Medicines Agency (EMA), 986 patients were candidates to treatment with PCSK9 inhibitors. However, following the prescription criteria issued by AIFA, only 180 patients were allowed to access to PCSK9 inhibitors before reimbursement criteria enlargement while 322 (+14.4%) with the current ones. Based on our observations, low-cost tailored therapeutic interventions for individual patients can significantly reduce the number of patients potentially needing treatment with PCSK9 inhibitors among those who are not allowed to access to the treatment. The application of enlarged reimbursement criteria for PCSK9 inhibitors could mildly improve possibility to adequately manage high-risk hypercholesterolemic subjects in the setting of an outpatient lipid clinic. [ABSTRACT FROM AUTHOR]

Introduction: Familial chylomicronemia syndrome (FCS) is a rare inherited disease, mainly due to lipoprotein lipase (LPL) gene mutations, leading to lipid abnormalities. Volanesorsen, a second-generation 2′-O-methoxyethyl (2′-MOE) chimeric antisense therapeutic oligonucleotide, can decrease plasma apolipoprotein C3 and triglycerides (TG) levels through LPL-independent pathways. The European Medicines Agency has approved volanesorsen as an adjunct to diet in adult FCS patients with an inadequate response to TG-lowering therapy. Areas covered: Available clinical data on volanesorsen efficacy and safety are presented. Furthermore, we discuss the yearly treatment with volanesorsen of a 21-year-old female FCS patient with LPL mutation. Volanesorsen was well-tolerated and decreased patient's TG levels (from >5000 mg/dL (56 mmol/L) to 350–500 mg/dL (4–5.6 mmol/L)) at 12 months. Lipoprotein apheresis (LA) was stopped and there were no episodes of pancreatitis or abdominal pain. Expert opinion: Severe hypertriglyceridemia can potentially be fatal. Until recently, there was no specific treatment for FCS, apart from hypotriglyceridemic diet, fibrates, omega-3 fatty acids, and LA sessions. Therefore, volanesorsen represents a promising therapeutic solution for these patients. The main side effect of volanesorsen therapy is thrombocytopenia, which should be monitored and treated accordingly. Increasing evidence will further elucidate the clinical implications of volanesorsen use in daily practice. [ABSTRACT FROM AUTHOR]