MBX 2109, a Once-Weekly Parathyroid Hormone Replacement Therapy Prodrug: Phase 1, First-in-Human, Randomized Trial.

Introduction: Hypoparathyroidism denotes parathyroid hormone (PTH) deficiency and impaired mineral metabolism. MBX 2109, a novel prodrug yielding a biologically active PTH peptide agonist (PTH[1-32], extended by a fatty acylated Lys33), is being developed as a long-acting, once-weekly PTH replacement therapy. Here, we report the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MBX 2109 in healthy volunteers.

Toward once-monthly insulin therapy synergy in two pharmacokinetic protractors: Fc-conjugation and fatty acid acylation.

Pharmacokinetic properties and duration of therapeutic action of a pharmaceutical agent can be significantly extended through the combination of two distinct strategies aimed at increasing plasma half-life: fatty acid acylation and Fc-conjugation. Using insulin as a case study, we demonstrate that a doubly protracted insulin analog produces a substantial prolongation of pharmacodynamic effect to lower blood glucose in STZ-treated mice when compared to the Fc-only counterparts. This enhancement is further corroborated by direct pharmacokinetic measurements in rat and dog models, demonstrating the potential for once-monthly insulin therapy.

Transforming obesity: The advancement of multi-receptor drugs.

For more than a century, physicians have searched for ways to pharmacologically reduce excess body fat. The tide has finally turned with recent advances in biochemically engineered agonists for the receptor of glucagon-like peptide-1 (GLP-1) and their use in GLP-1-based polyagonists. These polyagonists reduce body weight through complementary pharmacology by incorporating the receptors for glucagon and/or the glucose-dependent insulinotropic polypeptide (GIP).