Race for approval of first oral GLP-1R drug in obesity intensifies with four in phase III trials: GlobalData

In recent years, GLP-1 receptor (GLP-1R) products have gained immense popularity. Currently, four innovative GLP-1Rs are approved worldwide for obesity, all of which are injectables. This leaves a gap in the obesity market for an oral GLP-1R product. 63 drugs are in active development, with four Phase III products racing to earn the inaugural approval in this untapped market, says GlobalData.

Obesity, defined as excessive fat accumulation resulting from an imbalance between energy intake (diet) and expenditure (physical activity), has reached epidemic proportions. By 2030, half of all US adults are predicted to be obese (New England Journal of Medicine). This alarming trend presents a lucrative opportunity for drugmakers.

The success of GLP-1R-targeting drugs highlights their viability as a treatment approach. Currently, there are four innovative GLP-1Rs approved for obesity. This includes blockbuster drugs Novo Nordisk’s Wegovy and Saxenda, and Eli Lilly’s Zepbound. Shanghai Benemae Pharmaceutical’s Yishengtai is the final approved drug in this category.

However, all four mentioned products are approved as injectables. This route of administration is associated with negative attributes such as the requirement to attend a professional clinic, highlighting the appeal of oral alternatives, which offer convenience, lower development costs, and simpler marketing.  As such, companies are developing oral drugs with the intention of entering this untapped market.

Jasper Morley, Pharma Analyst at GlobalData states, “Novo Nordisk and Eli Lilly are looking to expand their GLP-1R portfolios and cement their positions as frontrunners within the oral GLP-1R for obesity category. Novo Nordisk is leading the pack with four separate products, two apiece in Phase III and Phase II. The company’s Phase III product Rybelsus, already FDA approved for cardiovascular risk factors and type 2 diabetes, is being positioned for a label expansion to include obesity. Additionally, Novo Nordisk’s novel Phase III candidate, NN-9932, which is expected to be launched by the end of 2025, has the highest probability of success among all drugs in this category, with a 35 per cent likelihood of approval (LoA).”

Morley adds, “Eli Lilly’s lone Phase III candidate, orforglipron calcium, has two firsts, becoming the initial oral GLP-1R approved for obesity and achieving the first GLP-1R approval for a small molecule. With a projected launch in 2026, it represents Eli Lilly’s bid to expand the company’s dominance in the GLP-1R category.”

China-based Jiangsu Hengrui’s HRS-9531 is the final Phase III contender and the only one not being developed by pharma giants Novo Nordisk or Eli Lilly. This highlights the increasing interest from global players in entering the competitive oral GLP-1R market.

Morley concludes, “With expected drug sales for GLP1Rs in obesity estimated to surpass $126 billion by 2030, this drug category presents a lucrative market for drug developers. Novo Nordisk and Eli Lilly have already reaped substantial rewards in the injectable segment. However, the emergence of oral therapies is reshaping the landscape.

“With 63 active products in the pipeline, the race for the first approval is intensifying. Nevertheless, Novo Nordisk and Eli Lilly are positioned at the forefront, striving to capitalise on their already successful GLP-1R portfolios and solidify their dominance in the GLP-1R market.”