Current and future development of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or simply GLP-1s, involves complexities not only in formulation but in all areas of early-phase drug development. Developing and refining preclinical models for early efficacy signals, developing and validating the bioanalytical assays necessary for quantitation, and designing the clinical studies that deliver the most robust data in this innovative therapeutic area are all key elements of a drug development program.

In Issue 42 of The Altascientist, we review the requirements for successful GLP-1 drug development, including:

• preclinical approaches 
• early-phase clinical study design 
• bioanalytical techniques 
• manufacturing 

Two case studies are also included. 

The Golden Era of GLP-1 Drugs

GLP-1 RAs are entero-pancreatic hormone-based treatments, first approved in 2005 for type 2 diabetes (T2D), and now commonly prescribed for weight loss and reduction of atherosclerotic cardiovascular (CV) risk in patients with T2D.

According to a MarketsandMarkets report from July 2024, the global GLP-1 market is expected to reach $471 billion worldwide by 2032. More than one billion people worldwide are living with obesity, which increases their risk of major health complications, including T2D, high blood pressure, heart disease, stroke, metabolic syndrome, fatty liver diseases, some cancers, kidney disease, breathing problems, and sleep apnea. Most of these diseases are interrelated, with glycemic control and weight loss being a major factor in improving the overall health of sufferers.

“As we learn more about GLP-1 RAs, we realize that they target many organ systems, including the pancreas, the stomach, brain, heart, kidneys, immune system (due to reduced inflammation), and skeletal muscle. They help control the metabolism of white and brown adipose tissue and show positive effect in fatty liver disease (nonalcoholic steatohepatitis, or NASH),” says Dr. Gaetano Morelli, Chief Medical Officer at Altasciences.

What We Know So Far About GLP-1 RAs

GLP-1 RA head-to-head clinical studies have demonstrated that all GLP-1 RAs are effective at reducing A1C (the average amount of glucose in a person’s blood over the past three months). The initial pivotal studies that led to the first wave of GLP-1 RAs demonstrated that they work in several ways, including stimulating insulin release, slowing digestion, reducing appetite, and inhibiting glucagon release. These actions have made GLP-1 RAs excellent candidates for obesity treatment, where much of the new development is now focused. As with most medical breakthroughs, the development and implementation of GLP-1 RA drugs is not straightforward. 

How Altasciences Can Help With Your GLP-1 Drug Development

Immunomodulatory drugs are at the forefront for the treatment of various types of cancer, infectious diseases, and numerous autoimmune diseases, including rheumatoid arthritis, type I diabetes, lupus, and multiple sclerosis. As the complexity of these therapeutics increases, so must the sophistication of the bioanalytical assays designed to either quantify them or measure their impact on the patient.

In Issue 41 of The Altascientist, we explore common classes of immunomodulators, bioanalytical methods used to quantify them, and their associated biomarkers. Featuring two scenarios that explore the complexities of bioanalysis for immunomodulators, The Altascientist offers practical considerations for ensuring accurate bioanalysis, as well as pharmacokinetic, pharmacodynamic, and safety data in clinical trials.

This issue also covers: 
•    classes of immunomodulators, including monoclonal antibodies, CAR-T cells, and vaccines;
•    immunotherapy trials, focusing on complex study designs and diverse patient populations; and
•    bioanalytical methods and assays, including pharmacokinetics and anti-drug antibodies (ADA).

Immunomodulation Assessments for Clinical Trials

Immunomodulators can be broadly defined as immunostimulants and immunosuppressants, with many types of modalities. The growing understanding of the immune system's role in various diseases, along with advancements in drug development, have led to a natural evolution from traditional vaccines, small molecules, and cytokines, to increased targeted biologics and innovative approaches in gene therapy and vaccines. 
 

“Each class of immunomodulator has a defined complexity and mechanism of action. Thus, the appropriate bioanalytical program will need to be carefully designed for the drug type and the intended purpose of the clinical study." –The Altascientist, Issue 41 pg. 2.

This includes careful consideration of pharmacokinetic and pharmacodynamic endpoints, as well as regulatory and bioanalytical requirements.

Particular attention is needed for monoclonal antibodies, CAR-T cells, antibody-drug conjugates (ADCs), and vaccines, as each class requires tailored strategies to support clinical studies and ensure accurate data collection.

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