AstraZeneca On Monday, it announced the competitive potential of its weight management pipeline at the Obesity Society’s ObesityWeek 2024 meeting in San Antonio, Texas, revealing the first data for oral GLP-1, a selective amylin agonist and fixed-dose combination therapy.

At the forefront of the pharmaceutical industry’s weight loss program is AZD5004, a small molecule oral GLP-1 receptor blocker. licensed from Shanghai-based biotech Eccogene in November 2023. AstraZeneca announced preliminary data for AZD5004 at ObesityWeek and touted the investigational pill’s clean safety profile.

AZD5004 in healthy participants Did not cause serious adverse eventsGastrointestinal toxicities became increasingly common at doses of 50 mg or greater. In type 2 diabetic patients receiving metformin therapy, AZD5004 caused more side effects, primarily of a gastrointestinal nature, compared to placebo; however, none of the side effects were serious.

GLP-1 resulted in 5.8% weight loss in type 2 diabetes patients after four weeks of treatment. Pharmacodynamic data showed that all tested doses of AZD5004 reduced fasting plasma glucose during the mixed meal tolerance test.

Jefferies analyst Peter Welford said initial AZD5004 data showed “tolerability” with “encouraging” pharmacokinetics.

AstraZeneca believes AZD5004 is “different” from other GLP-1 therapies in development and on the market, particularly given its “favorable tolerability,” BMO Capital Markets analyst Etzer Darout said in a note to investors. Further helping AZD5004 stand out in the crowded obesity field is its “reduction in glucose and body weight” and “simplified production pathway” in patients with type 2 diabetes, Darout wrote.

Also at ObesityWeek, AstraZeneca presented initial data for AZD6234, a long-acting amylin receptor agonist that, unlike most obesity therapies, targets the amylin pathway. achieve generally similar effectsIt delays gastric emptying, suppresses appetite and promotes the release of glucagon from the pancreas.

Phase I study of AZD6234 was well tolerated by healthy participantsNo deaths or serious adverse events were recorded. However, pooled global data showed that side effects were more common in patients treated with AZD6234 compared to placebo, most commonly nausea, vomiting and decreased appetite.

In terms of effectiveness, the first study showed that patients treated with subcutaneous AZD6234 experienced a “statistically significant reduction in body weight” compared to placebo.

According to Darout, AstraZeneca is positioning AZD6234 as an effective treatment alternative for patients intolerant to incretin therapies. Darout noted that preclinical data indicate that the presence of amylin may promote fat-selective weight loss. Other GLP-1 treatments have resulted in loss of lean muscle mass.

Darout commented that the AZD6234 ObesityWeek data was limited to “very little to create excitement, as expected.” Still, he said AstraZeneca is developing AZD6234 and AZD9550 as a potential fixed-dose combination therapy for patients with obesity. The combination of amylin and GLP-1/glucagon, which “aims to improve weight loss and organ protection,” is a potential once-weekly therapy for which Phase IIb trial planning is ongoing.

“We like AZN’s optionality for these programs, as well as their possible combination with other assets in the portfolio,” Darout said. But he added that until there is “further de-risking” of the pharma industry’s obesity portfolio (strong efficacy and clear safety data in larger studies), his firm will continue to adopt a more “conservative” revenue forecast of $865 million by 2032. Bemoan AstraZeneca’s $5 billion peak projection for its metabolic business.

“We are being more cautious given the early stage of development of these assets and expect to take more risk from the upcoming Phase II datasets,” Darout said.

Viking Therapeutics at ObesityWeek on Sunday explained Initial data from the first-in-human study of the investigational oral obesity drug VK2735 indicates robust weight loss in healthy adults and an encouraging safety profile.