Summary: In this Q&A with Dr. Andrew Lewis, Chief Scientific Officer, Matt Paterson, Chief Strategy Officer, and Dr. Andreas Reichl, Senior Drug Development Consultant, we discuss developments in this space and how we support clients to address drug product formulation and clinical testing of these therapies.
Interest in the development of new therapies to treat endocrine and metabolic diseases has skyrocketed, driven in part by increased commercial success and medical efficacy of GLP-1 agonists and other incretin hormones used to treat obesity in recent years.
As a result, research and development spending in metabolic disease therapies is now on par with oncology, making it one of the most sought-after areas in the pharmaceutical industry.
Q: What is fueling the tremendous growth of the metabolic drug market?
Dr. Andreas Reichl: Obesity rates have soared globally, tripling for women and quadrupling for men since 1975. The industry is responding, and there is currently a pipeline of over 300 obesity treatments in development. The market for obesity therapies alone is projected to surge from $2.4 billion in 2022 to as much as $100 billion by 2030.
Dr. Andrew Lewis: The success of GLP-1 agonists and incretin hormones in treating obesity is now being applied in other areas. Beyond obesity, there’s a broad spectrum: diabetes remains a common comorbidity, and cachexia (“wasting syndrome”), which often also affects cancer and HIV patients.
Q: Developing these therapies sounds complex. What are the main formulation and delivery challenges for new therapies to treat endocrine and metabolic diseases?
Dr. Andrew Lewis: Although injectable GLP-1 therapies work very well, they have faced hurdles in recent years. There have been various news stories regarding supply chain disruptions and challenges with maintaining patient adherence over extended time periods.
As I’ve discussed in past articles and at conferences, oral drugs are preferable for patients and are easier to produce, but oral GLP-1 have historically been tougher to formulate because of poor solubility or bioavailability. Many oral GLP-1s need permeation enhancers, and finding the right ratio and dosing schedule can be a challenge. Achieving effective plasma levels with once-daily dosing can take extensive testing.
Dr. Andreas Reichl: Another key challenge is bridging the gap between animal models and human results, especially for pharmacokinetics. It takes ingenuity and rigorous science to get it right.
Q: How do clinical trials in this space differ, and what strategies help ensure success for new therapies to treat endocrine and metabolic diseases?
Dr. Andreas Reichl: Trials often run for long periods, as safe weight loss and body composition changes take time. Patient retention is a big concern, and there are of course instances where adverse events and slow results discourage participation.
We use trial designs like lead-in phases and dose escalation to build tolerance, plus pharmacodynamic endpoints for early efficacy reads. Engaging patients through support groups, dietary counseling, and proactive communication is vital for retention.
The overall patient experience must be front and center. Minimizing burdens and improving engagement increase both participation and the value of trial data.
Q: What sets Quotient Sciences’ services apart from other CDMO or CRO addressing metabolics?
Matt Paterson: Quotient Sciences has supported metabolic drug development for a number of years. Taking a fully integrated approach has been one aspect constantly setting us apart from other vendors, with formulation development, manufacturing, and clinical capabilities within the same organization.
We’re among the few industry partners able to offer developers a fully integrated model—Translational Pharmaceutics®, our platform for accelerated drug development that we’ve applied to client programs for almost two decades.
How we bring together multidisciplinary teams is another point I’d raise that sets Quotient Sciences apart. Drug development consultants, formulation scientists, regulatory and quality assurance specialists, and data science professionals are among the Quotient Sciences colleagues who are assembled to support a project. They are all coordinated by a dedicated project manager, and this model ensures activities can run in parallel and stay coordinated.
Dr. Andrew Lewis: Oral peptides is an application where Translational Pharmaceutics® has stood out, and our experience in this space continues to evolve. We’ve worked on over 14 oral peptide programs over the last decade, and that has included evaluating 10 different permeation enhancers, including modeling & simulation studies on the effect of a permeation enhancer.
It’s worth adding that our expertise in overcoming CMC challenges for both injectable and oral peptides, and our proficiency in clinical pharmacology, played a critical role in supporting development of Novo Nordisk’s Rybelsus®.
Matt Paterson: We’ve often heard from clients how seeing Translational Pharmaceutics® applied is a real eye-opening experience. When compared to “traditional” methods of development, we’re able to support clients in achieving milestones faster, with greater precision and confidence.
For more insight about Quotient Sciences’ experience, download our recent whitepaper, “How to Capture Growth in the Expanding Metabolic Drug Market.”
i Baekdal TA, Donsmark M, Hartoft-Nielsen ML, Søndergaard FL, Connor A. “Relationship Between Oral Semaglutide Tablet Erosion and Pharmacokinetics: A Pharmacoscintigraphic Study.” Clin Pharmacol Drug Dev. 2021 May;10(5):453-462. doi: 10.1002/cpdd.938. Epub 2021 Mar 22. PMID: 33750044; PMCID: PMC8251533. https://pubmed.ncbi.nlm.nih.gov/33750044