AstraZeneca's oral GLP-1 receptor agonist (GLP-1RA) AZD5004 is showing encouraging results in early-stage trials, offering a potential alternative to injectable therapies for obesity and type 2 diabetes. The Phase I study, presented at ObesityWeek, demonstrated a favorable safety profile and promising efficacy, paving the way for Phase IIb trials.
Phase I Trial Results
The Phase I trial evaluated AZD5004 in 72 healthy, non-obese individuals and patients with type 2 diabetes. The drug was found to be safe at doses below 50 mg, with higher doses leading to increased gastrointestinal side effects, consistent with other GLP-1RA medications. Participants experienced an average weight loss of 5.8% over four weeks, alongside improvements in fasting plasma glucose levels.
"We saw a dose-dependent increase in nausea and vomiting consistent with molecules in this class," said Sharon Barr at a briefing during ObesityWeek.
Advancement to Phase IIb
Based on these promising results, AZD5004 is now being evaluated in two Phase IIb studies. The Vista study will focus on obesity, enrolling 304 participants with an expected completion date in late 2025. The Solstice study will investigate AZD5004 in 384 patients with type 2 diabetes, with results anticipated in early 2026.
Strategic Combination Therapy
AstraZeneca is also exploring a combination therapy approach, pairing AZD5004 with AZD6234, a long-acting amylin analogue currently in a Phase IIb weight loss trial. The company hopes that combining these two drugs will result in more targeted and effective fat loss. While the timeline for this combination trial remains unclear, Sharon Barr stated that the "encouraging Phase I data provided confidence for the combination strategy."
Market Context
AstraZeneca licensed AZD5004 from Eccogene in 2023 for nearly US$2 million, anticipating potential sales of $800 million by 2032 if development progresses successfully. While AstraZeneca lags behind Novo Nordisk and Eli Lilly in the obesity drug market, the demand for such medications, particularly in oral form, suggests ample opportunity for new entrants. Viking Therapeutics also presented early-stage results from a trial of its oral obesity candidate VK2735, reporting up to an average of 8.2% weight loss over 28 days at the highest tested dose of 100 mg.
"We believe this oral GLP-1RA molecule could offer alternatives to current injectable therapies both as a potential monotherapy as well as in combination for cardiometabolic diseases such as type 2 diabetes, as well as for obesity," Sharon Barr said when the deal with Eccogene was struck.
