AstraZeneca presented early data at The Obesity Society’s ObesityWeek 2024 in San Antonio, Texas, highlighting the potential of its weight management pipeline, including the oral GLP-1 receptor agonist AZD5004 and the selective amylin agonist AZD6234. These early findings suggest promising avenues for obesity treatment, with a focus on tolerability and novel combination therapies.
AZD5004: Oral GLP-1 Receptor Agonist
AZD5004, licensed from Eccogene in November 2023, is a small molecule oral GLP-1 receptor agonist. Early data from studies involving healthy participants and type 2 diabetes patients on metformin showed a clean safety profile, with gastrointestinal toxicities increasing at doses of 50 mg or higher. In type 2 diabetes patients, AZD5004 resulted in a 5.8% weight loss after four weeks. Pharmacodynamic data indicated that all tested doses of AZD5004 lowered fasting plasma glucose during a mixed meal tolerance test.
According to Jefferies analyst Peter Welford, the initial AZD5004 data showcase tolerability with encouraging pharmacokinetics. BMO Capital Markets analyst Etzer Darout noted that AstraZeneca believes AZD5004 is differentiated by its favorable tolerability, reduction in glucose and body weight in type 2 diabetes patients, and simplified manufacturing path.
AZD6234: Long-Acting Amylin Receptor Agonist
AZD6234 is a long-acting amylin receptor agonist designed to delay gastric emptying, suppress appetite, and promote glucagon release. Phase I study results demonstrated that AZD6234 was well-tolerated by healthy participants, with no deaths or serious adverse events. However, side effects, mainly nausea, vomiting, and decreased appetite, were more common in AZD6234-treated patients compared to placebo. Efficacy data showed a statistically significant decrease in body weight in patients treated with subcutaneous AZD6234 compared to placebo.
AstraZeneca is positioning AZD6234 as an alternative for patients intolerant to incretin therapies. Preclinical data suggest that the amylin asset could promote fat-selective weight loss, addressing the lean muscle mass loss seen with other GLP-1 therapies. Darout commented that the AZD6234 data were limited, but AstraZeneca is developing AZD6234 and AZD9550 as a potential fixed-dose combination therapy for obesity, aiming to improve weight loss and organ protection with a potential once-weekly administration; Phase IIb trial planning is underway.
Future Outlook
Despite the promising early data, analysts remain cautiously optimistic. Darout indicated that further de-risking through strong efficacy and clean safety data in larger studies is needed before adopting less conservative revenue estimates. His firm maintains a more conservative revenue estimate of $865 million by 2032, compared to AstraZeneca’s $5 billion peak projection for its metabolic business, pending upcoming Phase II datasets.
