USA – AstraZeneca has unveiled new developments in its weight management pipeline, presenting early data for three promising therapies aimed at tackling obesity and its associated metabolic challenges at ObesityWeek 2024, held in San Antonio, Texas.
Among these, AZD5004, a small-molecule oral GLP-1 receptor blocker, AZD6234, a long-acting amylin receptor agonist, and a potential fixed-dose combination therapy were highlighted as key innovations in AstraZeneca’s growing obesity portfolio.
AstraZeneca’s leading contender, AZD5004, stands out as a groundbreaking oral GLP-1 receptor blocker licensed from Eccogene in November 2023.
This therapy is currently undergoing evaluation in Phase 2b trials for both obesity and type 2 diabetes, with results expected by the end of 2025 and early 2026.
Early clinical data presented at ObesityWeek highlighted AZD5004’s safety profile, showing no serious adverse events in healthy participants.
However, gastrointestinal side effects like nausea became more prevalent at doses of 50 mg and above.
In patients with type 2 diabetes on metformin, AZD5004 also resulted in gastrointestinal issues, though these were not severe.
Importantly, the therapy demonstrated a significant 5.8% weight loss after four weeks of treatment and proved effective in lowering fasting plasma glucose levels, adding value for diabetes management.
AstraZeneca’s Sharon Barr, EVP of Biopharmaceuticals R&D, noted the company’s forward-thinking approach to integrating AZD5004 with other approved medications: “Recognizing and targeting the interconnectedness of diseases such as chronic kidney disease, heart failure, high cholesterol, and type 2 diabetes will help us to create more effective and holistic treatments.”
AZD6234: Targeting Amylin for effective weight loss
Another promising asset presented at ObesityWeek was AZD6234, a long-acting amylin receptor agonist designed to address obesity through a novel mechanism.
Unlike typical obesity treatments, AZD6234 targets the amylin pathway, delaying gastric emptying, suppressing appetite, and stimulating glucagon release from the pancreas.
Early Phase I study results indicated that AZD6234 was well-tolerated by healthy participants, with no serious adverse events.
However, mild side effects such as nausea, vomiting, and decreased appetite were more common in AZD6234-treated patients compared to the placebo group.
Despite these side effects, the treatment demonstrated a statistically significant reduction in body weight.
According to BMO Capital Markets’ analyst Etzer Darout, AZD6234 could be an effective alternative for patients who are intolerant to traditional incretin therapies like GLP-1 treatments.
He further emphasized that preclinical data suggest AZD6234 could promote fat-selective weight loss, distinguishing it from other therapies that may lead to the loss of lean muscle mass.
Potential combination therapy
AstraZeneca is also exploring the possibility of combining AZD6234 with its GLP-1 and glucagon therapies, including AZD9550, to create a once-weekly, fixed-dose combination treatment.
This combination aims to maximize weight loss while offering organ protection, which is critical for patients dealing with obesity-related metabolic issues.
A Phase IIb trial for this combination therapy is currently in the planning stages, with AstraZeneca positioning it as a potential breakthrough for patients with complex metabolic needs.
Darout added that the company’s focus on combining these therapies could help set AstraZeneca apart in the competitive weight loss market.
“These combinations aim to improve both weight loss and organ protection,” Darout noted. “It’s a critical consideration for patients with obesity-related metabolic issues.”
