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Archive - Nov 26, 2018

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FDA Approves ACTpen for Genentech’s ACTEMRA, a Single-Dose, Prefilled Autoinjector for Treatment of Rheumatoid Arthritis, Giant Cell Arteritis, & Two Forms of Juvenile Arthritis

On November 26,2018, Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced that the U.S. Food and Drug Administration (FDA) has approved ACTPen™ 162 mg/0.9 mL, a single-dose prefilled autoinjector for Actemra® (tocilizumab) as an additional formulation for adult patients with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs), and for adult patients with giant cell arteritis (GCA). Further, the ACTPen can be administered by caregivers to patients two years of age and older with active polyarticular juvenile idiopathic arthritis (PJIA) or active systemic juvenile idiopathic arthritis (SJIA). The ability of pediatric patients to self-inject with the ACTPen has not been tested. The ACTPen is expected to be available in January 2019. “When it comes to the administration of medicines, we believe patients should have choices, when possible,” said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development for Roche/Genentech. “With ACTPen for Actemra, we are pleased to offer an additional option to patients who may prefer using the new autoinjector over other formulations.”The FDA first approved Actemra intravenous infusion formulation (IV) for adults with RA in January 2010 and Actemra pre-filled syringe (PFS) formulations for subcutaneous injection (SC) for adults with RA in October 2013. In May 2017, Actemra SC became the first therapy approved by the FDA for the treatment of adult patients with GCA, a chronic and severe form of vasculitis characterized by inflammation of certain large blood vessels.

Perivascular Dendritic Cells Elicit Anaphylaxis by Relaying Allergens to Mast Cells Via Microvesicles

In work published online on November 9, 2018, in Science, Duke University Medical Center researchers, and colleagues, demonstrate that IgE-sensitized mast cells (MCs) (image) are indirectly activated by blood-borne allergens. In addition, the study revealshow perivascular dendritic cells (DCs) continuously sample blood and initiated and markedly enhance inflammatory and immune responses by rapidly discharging antigen-bearing microvesicles (MVs) to surrounding immune cells. the Science article is titled “Perivascular Dendritic Cells Elicit Anaphylaxis by Relaying Allergens to Mast Cells Via Microvesicles.” The results may resolve the conundrum of how mast cells, which are extravascular, are able to perceive and react to blood-borne allergens. The scientists describe the existence of a CD301b+ perivascular DC subset that continuously samples blood and relays antigens to neighboring MCs, which vigorously degranulate and trigger anaphylaxis. DC antigen transfer involved the active discharge of surface-associated antigens on 0.5- to 1.0-micrometer MVs generated by vacuolar protein sorting 4 (VPS4). Antigen sharing by DCs is not limited to MCs, as neighboring DCs also acquire antigen-bearing MVs. This capacity of antigen-bearing MVs to various immune cells in the perivascular space potentiates inflammatory and immune responses to blood-borne antigens. Anaphylaxis is a life-threatening allergic reaction triggered after antigen-specific immunoglobulin E (IgE) antibodies bind to target allergens. These antibodies than cross-link IgE-specific Fc receptors on the surface of MCs. The MCs rapidly release inflammatory mediators, including histamine, resulting in smooth muscle contraction, vasodilation, and blood vessel leakage.

Exosome-Like Nanoparticles (ELNs) Derived from Plants Are Taken Up by Mouse Gut Microbiota and Can Ameliorate Disease

In work published in the November 14, 2018 issue of Cell Host & Microbe, researchers from the James Graham Brown Cancer Center, Department of Microbiology & Immunology, University of Louisville in Kentucky, together with colleagues, demonstrate that plant-derived exosome-like nanoparticles (ELNs) are taken up by the gut microbiota and contain RNA that alter the mouse microbiome composition and host physiology. The article is titled “Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota.” Specifically, the authors show that ginger ELNs (GELNs) are preferentially taken up by Lactobacillaceae in a GELN lipid-dependent manner and contain microRNAs (miRNAs) that target various genes in Lactobacillus rhamnosus (LGG). In particular, the authors noted that the GELN mdo-miR7267-3p-mediated targeting of the LGG monooxygenase ycnE yields increased indole-3-carboxaldehyde (I3A). GELN-RNAs or I3A, a ligand for aryl hydrocarbon receptor, are sufficient to induce production of IL-22, which is linked to barrier function improvement. According to the authors, these functions of GELN-RNAs can ameliorate mouse colitis via IL-22-dependent mechanisms. The authors conclude that their findings indicate how plant products and their effects on the microbiome can be used to target specific host processes to alleviate disease. Note that the image here was taken from the article abstract and can be much better viewed at the abstract itself (at the link below).

[Cell Host & Microbe abstract]