M281 is a fully human, anti‐neonatal Fc receptor (FcRn) antibody that inhibits FcRn‐mediated immunoglobulin G (IgG) recycling to decrease pathogenic IgG while preserving IgG production. A randomized, double‐blind, placebo‐controlled, first‐in‐human study with 50 normal healthy volunteers was designed to probe safety and the physiological maximum for reduction of IgG. Intravenous infusion of single ascending doses up to 60 mg/kg induced dose‐dependent serum IgG reductions, which were similar across all IgG subclasses. Multiple weekly doses of 15 or 30 mg/kg achieved mean IgG reductions of ≈85% from baseline and maintained IgG reductions ≥75% from baseline for up to 24 days. M281 was well tolerated, with no serious or severe adverse events ( AE s), few moderate AE s, and a low incidence of infection‐related AE s similar to placebo treatment. The tolerability and consistency of M281 pharmacokinetics and pharmacodynamics support further evaluation of M281 in diseases mediated by pathogenic IgG.

Conventional cytotoxic chemotherapy is highly effective in certain cancers, but causes dose-limiting damage to normal proliferating cells, especially hematopoietic stem and progenitor cells (HSPCs). Serial exposure to cytotoxics causes a long-term hematopoietic compromise (‘exhaustion’), which limits the use of chemotherapy and success of cancer therapy. Here, we show that the co-administration of G1T28 (trilaciclib), a small-molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), contemporaneously with cytotoxic chemotherapy protects murine hematopoietic stem cells (HSCs) from chemotherapy-induced exhaustion in a serial 5-fluorouracil (5FU) treatment model. Consistent with a cell intrinsic effect, we show directly preserved HSC function resulting in a more rapid recovery of peripheral blood counts, enhanced serial transplantation capacity and reduced myeloid skewing. When administered to healthy human volunteers, G1T28 demonstrated excellent in vivo pharmacology and transiently inhibited bone marrow (BM) HSPC proliferation. These findings suggest that the combination of CDK4/6 inhibitors (CDK4/6i) with cytotoxic chemotherapy should provide a means to attenuate therapy-induced BM exhaustion in patients with cancer.

Vorapaxar provided rapid and sustained dose-related inhibition of platelet aggregation without affecting bleeding or clotting times.

The pharmacokinetic data support coadministration of daclatasvir with atazanavir/ritonavir, efavirenz and/or tenofovir. A Phase III study in HIV-HCV coinfection has commenced using the described dose modifications.

Co-administration of ezetimibe 10 mg with rosuvastatin 10 mg daily caused a significant incremental reduction in LDL-C compared with rosuvastatin alone. Moreover, co-administering ezetimibe and rosuvastatin was well tolerated in patients with hypercholesterolemia.