Drugs of today
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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.
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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.
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Tapentadol exerts its analgesic effects through micro opioid receptor agonism and noradrenaline reuptake inhibition in the central nervous system. Preclinical studies demonstrated that tapentadol is effective in a broad range of pain models, including nociceptive, inflammatory, visceral, mono- and polyneuropathic models. ⋯ In addition, it was reported to be associated with significantly fewer treatment discontinuations due to a significantly lower incidence of gastrointestinal-related adverse events compared with equivalent doses of oxycodone. The combination of these reduced treatment discontinuation rates and tapentadol efficacy for the relief of moderate to severe nociceptive and neuropathic pain may offer an improvement in pain therapy by increasing patient compliance with their treatment regimen.
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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.