Drugs of today
-
In May of 2019, the adeno-associated virus (AAV)-based gene therapy onasemnogene abeparvovec-xioi (Zolgensma) became the second Food and Drug Administration (FDA)-approved gene therapy with designated use for infants diagnosed with spinal muscular atrophy (SMA). The decision came nearly 10 years after results of the first preclinical models were initially reported. While the journey was an arduous one, the approval was an indication of the remarkable success of the first in-human clinical trials. ⋯ Children with SMA type 1 cannot lift their heads without assistance and do not live past their second birthday. With Zolgensma, the first treated children with SMA type 1 have reached 5 years of age and some of them achieved the ability to sit unassisted or even walk. In this article, we review the work that led to FDA approval with emphasis on the development of preclinical and clinical studies.
-
Hepatocellular carcinoma (HCC) is a worldwide problem, with a high prevalence in nonindustrialized countries and a rising incidence in industrialized countries. Its close association with chronic liver diseases and liver cirrhosis represents a significant challenge in its treatment. ⋯ The therapeutic scenario changed dramatically in 2020, when the combination of atezolizumab and bevacizumab proved to be significantly superior to sorafenib and, thus, establishing a new standard of care. In this monograph we provide an update about the safety and efficacy of atezolizumab reported in the clinical trials of HCC, as monotherapy or in combination with other agents.
-
Porphyrias are a family of rare diseases chiefly due to inborn errors of heme biosynthesis. The porphyrias are generally characterized either by the main site of overproduction of heme precursors (hepatic or erythropoietic) or the main clinical manifestations (acute or cutaneous). The regulation of 5- (or δ)-aminolevulinic acid synthase 1 (ALAS1) plays a key role in the pathway of normal hepatic heme synthesis, providing insight into the pathophysiologic mechanisms and potential therapeutic targets for the treatment of the porphyrias. ⋯ S. Food and Drug Administration (FDA) for the treatment of adult patients with AHP, and it received also approval in the E. U. in 2020 for the treatment of AHP in adults and adolescents aged 12 years and older.
-
Ebola virus (EBOV) causes outbreaks of lethal febrile illness in Africa, the largest of which resulted in over 11,000 deaths and represented a global public health threat. A new biomedical countermeasure, the recombinant vesicular stomatitis virus expressing EBOV glycoprotein (rVSV-EBOV) has been licensed (Ervebo; Merck & Co.). rVSV-EBOV is a replicative viral vaccine engineered to express EBOV antigen. ⋯ The vaccine has a good safety profile, but is associated with self-limited arthritis and rash in a minority of recipients. rVSV-EBOV is highly immunogenic after a single intramuscular dose with antibody titers persisting for at least 2 years. In the recent outbreak in the Democratic Republic of the Congo, rVSV-EBOV was administered to more than 300,000 individuals and may have contributed, at least in part, to controlling the epidemic.
-
Randomized Controlled Trial
Upadacitinib tartrate in rheumatoid arthritis.
In rheumatoid arthritis (RA) there is an unmet therapeutic need, as a substantial proportion of patients does not achieve low disease activity or remission despite the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or biological DMARDs (bDMARDs). The Janus kinase (JAK) inhibitors are the most recently added drug category in the therapeutic armamentarium in RA. Upadacitinib tartrate (Rinvoq), a selective and reversible JAK1 inhibitor, inhibited interleukin (IL)-6 and IL-7 and ameliorated adjuvant-induced arthritis in preclinical studies. ⋯ Upadacitinib has a good safety profile but it may increase the risk for herpes zoster, and as a substrate of cytochrome P450 (CYP) enzyme CYP3A4 it should not be coadministered with strong CYP3A4 inducers. Upadacitinib is contraindicated in patients with active tuberculosis, serious infections, active malignancy and in patients with severe liver impairment. Upadacitinib has been approved for the treatment of moderate to severe RA.