The New England journal of medicine
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Cachexia is a common complication of cancer and is associated with an increased risk of death. The level of growth differentiation factor 15 (GDF-15), a circulating cytokine, is elevated in cancer cachexia. In a small, open-label, phase 1b study involving patients with cancer cachexia, ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed serum GDF-15 levels. ⋯ Among patients with cancer cachexia and elevated GDF-15 levels, the inhibition of GDF-15 with ponsegromab resulted in increased weight gain and overall activity level and reduced cachexia symptoms, findings that confirmed the role of GDF-15 as a driver of cachexia. (Funded by Pfizer; ClinicalTrials.gov number, NCT05546476.).
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Randomized Controlled Trial Multicenter Study
Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia.
Angiopoietin-like 3 (ANGPTL3) inhibits lipoprotein and endothelial lipases and hepatic uptake of triglyceride-rich lipoprotein remnants. ANGPTL3 loss-of-function carriers have lower levels of triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol and a lower risk of atherosclerotic cardiovascular disease than noncarriers. Zodasiran is an RNA interference (RNAi) therapy targeting expression of ANGPTL3 in the liver. ⋯ In patients with mixed hyperlipidemia, zodasiran was associated with significant decreases in triglyceride levels at 24 weeks. (Funded by Arrowhead Pharmaceuticals; ARCHES-2 ClinicalTrials.gov number, NCT04832971.).