Eli Lilly (United States)

Image-Based Quantification of Amorphous Solid Dispersion Tablet Formulation Disintegration Profiles in a Custom USP-2 Apparatus

Abstract Amorphous solid dispersions (ASDs) are single-phase molecular mixtures of amorphous drug and polymer designed to enhance solubility, inhibit crystallization, and improve release rate, increasing bioavailability. During dissolution, water lowers the glass-transition tempe...

Pregnancy outcomes following exposure to galcanezumab: Analysis of cases from the galcanezumab clinical trials and postmarketing database

OBJECTIVE: This study was conducted to describe pregnancy outcomes reported following maternal or paternal exposure to galcanezumab in clinical trials and postmarketing surveillance. BACKGROUND: Galcanezumab is a calcitonin gene-related peptide-inhibiting monoclonal antibody indi...

Indirect comparative efficacy and safety of tirzepatide vs semaglutide for the treatment of obesity or overweight in patients without type 2 diabetes

Tirzepatide is a once-weekly, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) for obesity treatment. This indirect treatment comparison (ITC) assessed the relative efficacy and safety of tirzepatide versus the GLP-1 RA semagl...

Revealing Nanomedicine Design Principles for Efficient siRNA Delivery to the Central Nervous System

Abstract A series of polymer nanocapsules were designed and synthesized for non-viral siRNA delivery to the central nervous system via intracerebroventricular injection. Various factors can contribute to superior diffusion profiles. In this study, we find that size, charge, and m...

Toward the Development of a Commercial Process to Produce Muvalaplin. Part II: Preparation of the Drug Substance

Abstract Herein, we describe the development of steps 5–7 for a large-scale process to synthesize muvalaplin, a small-molecule lipoprotein(a) inhibitor for the potential reduction of major adverse cardiovascular events in participants with established cardiovascular disease or at...

The RobinCar Family: R tools for robust covariate adjustment in randomized clinical trials

Abstract Purpose Covariate adjustment is a powerful statistical technique that can increase efficiency in clinical trials. Recent guidance from the U.S. Food and Drug Association (FDA) provided recommendations and best practices for using covariate adjustment. However, there has...

Voltage-gated sodium channel, Nav 1.8, regulates calcium dynamics in the dorsal root ganglion induced by cold nociceptive stimulus

Nociceptive pain responses are mediated by neurons in the dorsal root ganglion. Certain voltage-gated sodium channels, such as Na v 1.8, are necessary for action potential firing and sensing pain. Prior work has demonstrated that interfering with voltage-gated calcium channel act...

The pandemic and the shift in social dynamics: how well do existing theoretical frameworks explain volunteering during COVID-19?

This study examines how well existing theoretical frameworks explain formal volunteering amid a public health crisis, focusing on dominant status, social networks, role constraints, and risk perceptions. Grounded in these four theoretical frameworks, the study tests whether the r...

Glycemic and bodyweight effects of GIPR coding variation reflect differences in surface expression and intrinsic functional impairment

The glucose-dependent insulinotropic polypeptide receptor (GIPR) is a major therapeutic target in type 2 diabetes and obesity. Missense variation in GIPR could confer phenotypic effects through alterations to constitutive activity or functional responses to GIP or pharmacological...

A Review on Lymphatic Uptake of Large Therapeutic Proteins after Subcutaneous Injection

Subcutaneous (SC) administration has emerged as a promising route for delivering large therapeutic proteins, offering advantages such as improved patient convenience and reduced healthcare costs. However, the mechanisms that regulate the uptake of these macromolecules are not yet...

Tiny Messengers, Actionable Targets: sEV-Driven Epigenetic Changes in Cancer

Small extracellular vesicles (sEVs) are pivotal mediators of intercellular epigenetic communication in cancer. Following MISEV2023, we use the size- and isolation-based term sEV throughout, because most primary studies cited here cannot resolve which biogenetic route generated th...

Liver Fat Changes in Patients With Type 2 Diabetes by Presence of Genetic Hepatic Steatosis: A Post Hoc Analysis of SURPASS ‐3 MRI

ABSTRACT The patatin‐like phospholipase 3 (PNPLA3) I148M genetic variant is highly associated with steatotic liver disease. In the SURPASS‐3 MRI substudy, tirzepatide significantly reduced liver fat content (LFC) versus insulin degludec in insulin‐naïve patients with type 2 diabe...

BE-BOIN: A Dose Optimization Design Accommodating Backfill and Late-Onset Toxicity

The US Food and Drug Administration (FDA) launched Project Optimus and issued guidance to reform dose-finding and selection trials, shifting the paradigm from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), which optimizes the risk a...