AstraZeneca Strengthens Obesity Development Portfolio with Encouraging Initial Results for Treatment Candidates
AstraZeneca recently showcased the promising potential of its weight management development at The Obesity Society’s ObesityWeek 2024 event in San Antonio, Texas. The company shared preliminary findings for its oral GLP-1, a selective amylin agonist, and a fixed-dose combination therapy.
Heading AstraZeneca’s weight loss initiative is AZD5004, an oral GLP-1 receptor blocker acquired in November 2023 from Eccogene, a biotech firm based in Shanghai. At ObesityWeek, early results for AZD5004 were presented, highlighting a favorable safety profile for this investigational medication.
The data showed that AZD5004 did not lead to serious adverse events in healthy subjects, though gastrointestinal issues emerged more frequently at dosages equal to or exceeding 50 mg. In patients with type 2 diabetes receiving metformin, AZD5004 produced more side effects compared to placebo, primarily gastrointestinal, but none were serious.
Type 2 diabetes patients experienced a weight loss of 5.8% after just four weeks of treatment with the GLP-1. The pharmacodynamic analysis revealed that AZD5004 led to decreased fasting plasma glucose during a mixed meal tolerance test across all tested dosages.
Jefferies analyst Peter Welford praised the initial findings of AZD5004, noting its “encouraging” pharmacokinetics and overall tolerability.
BMO Capital Markets analyst Etzer Darout noted in a communication to investors that AstraZeneca considers AZD5004 to be “differentiated” from other GLP-1 treatments, especially due to its desirable tolerability profile. The drug’s ability to lower both glucose levels and body weight in type 2 diabetes patients, alongside a streamlined manufacturing process, helps it stand out, according to Darout.
In addition to AZD5004, AstraZeneca introduced early findings for AZD6234, its long-acting amylin receptor agonist that targets the amylin pathway, offering effects such as delayed gastric emptying, appetite suppression, and enhanced glucagon release from the pancreas similar to other obesity medications.
The Phase I trial indicated that AZD6234 was well-tolerated among healthy participants, with no severe adverse events reported. However, the overall data indicated a higher frequency of side effects in patients treated with AZD6234 compared to the placebo group, mainly consisting of nausea, vomiting, and reduced appetite.
Effectiveness-wise, the early results demonstrated a “statistically significant decrease in body weight” in subcutaneous AZD6234 patients relative to those given placebo.
AstraZeneca is strategizing to position AZD6234 as a viable treatment option for those unable to tolerate incretin therapies. Darout noted that preclinical studies suggest the amylin-based drug could promote fat-specific weight reduction, contrasting with other GLP-1 therapies that often cause loss of lean muscle mass.
Darout remarked that the findings for AZD6234 from ObesityWeek were modest, providing “little to incite excitement.” Nonetheless, AstraZeneca is advancing the development of AZD6234 alongside AZD9550 as a potential fixed-dose therapy option for obesity patients. This combination of amylin and GLP-1/glucagon aims to enhance weight loss and organ protection and is expected to lead to a once-weekly treatment, with a Phase IIb trial already in the planning stages.
“We appreciate AstraZeneca’s potential for these programs and possible combinations with other elements in their portfolio,” stated Darout. However, he expressed that until the company’s obesity portfolio demonstrates robustness through effective safety and efficacy data in broader studies, his firm would adopt a cautious revenue forecast of 5 million by 2032, significantly less than AstraZeneca’s billion peak expectations for its metabolic department.
“We are taking a conservative stance owing to these assets’ early development stages and are awaiting further validation from upcoming Phase II data sets,” Darout concluded.
During ObesityWeek on Sunday, Viking Therapeutics unveiled early findings from the first-in-human trial of its investigational oral obesity treatment VK2735, which demonstrated significant weight loss in healthy adults alongside an encouraging safety profile.