While expected and seen as largely incremental, Jefferies analyst Peter Welford in a Tuesday note to investors said the detailed data for three early-stage assets support moving them into Phase IIb studies and creates a “foothold” for AstraZeneca in the weight loss space.
AstraZeneca on Monday touted the competitive potential of its weight management pipeline at The Obesity Society’s ObesityWeek 2024 meeting in San Antonio, Texas, revealing early data for its oral GLP-1, a selective amylin agonist and a fixed-dose combination therapy.
Leading the pharma’s weight loss program is AZD5004, a small molecule oral GLP-1 receptor blocker licensed in November 2023 from Shanghai-based biotech Eccogene. At ObesityWeek, AstraZeneca unveiled early data for AZD5004, touting a clean safety profile for the investigational pill.
AZD5004 in healthy participants did not result in serious adverse events, while gastrointestinal toxicities became increasingly common at doses at or above 50 mg. In type 2 diabetes patients on metformin treatment, AZD5004 led to more side effects than placebo, particularly gastrointestinal in nature—though none of the side effects were serious.
The GLP-1 resulted in 5.8% weight loss after four weeks of treatment in type 2 diabetes patients. Pharmacodynamic data showed that all tested doses of AZD5004 lowered fasting plasma glucose during a mixed meal tolerance test.
Jefferies analyst Peter Welford said the initial AZD5004 data “showcase tolerability” with “encouraging” pharmacokinetics.
BMO Capital Markets analyst Etzer Darout in a note to investors said that AstraZeneca believes that AZD5004 is “differentiated” from other GLP-1 therapies in development and on the market, particularly given its “favorable tolerability.” Further helping AZD5004 distinguish itself in the crowded obesity space is its “reduction in glucose and body weight” in patients with type 2 diabetes and its “simplified manufacturing path,” Darout wrote.
Also at ObesityWeek, AstraZeneca presented early data for AZD6234, its long-acting amylin receptor agonist which, unlike most obesity therapies, targets the amylin pathway but is designed to achieve broadly similar effects—delay gastric emptying, suppress appetite and promote the release of glucagon from the pancreas.
The Phase I study demonstrated that AZD6234 was well-tolerated by healthy participants, with no deaths or serious adverse events recorded. However, pooled global data showed that side effects were more common in AZD6234-treated patients versus placebo, with mostly episodes of nausea, vomiting and decreased appetite.
In terms of efficacy, the early study showed that patients treated with subcutaneous AZD6234 experienced a “statistically significant decrease in body weight” compared with placebo.
AstraZeneca is positioning AZD6234 as an effective treatment alternative for patients who are intolerant to incretin therapies, according to Darout, who noted that preclinical data indicate that the amylin asset could promote fat-selective weight loss. Other GLP-1 therapies have resulted in the loss of lean muscle mass.
Darout commented that the AZD6234 ObesityWeek data were limited with “little to build enthusiasm as expected.” Still, he said AstraZeneca is developing AZD6234 and AZD9550 as a potential fixed-dose combination therapy for patients with obesity. The amylin and GLP-1/glucagon combo, which “aims to improve weight loss and organ protection,” is a potential once-weekly therapy with Phase IIb trial planning underway.
“We like AZN’s optionality for these programs as well as potential combinations with other assets in the portfolio,” Darout said. However, he added that until “further de-risking” of the pharma’s obesity portfolio—through strong efficacy and clean safety data in larger studies—his firm will continue to adopt a more “conservative” revenue estimate of $865 million by 2032, a far cry from AstraZeneca’s $5 billion peak projection for its metabolic business.
“We’re more conservative given the earlier stage of development of these assets and look to further de-risking from upcoming Phase II datasets,” Darout said.
At ObesityWeek on Sunday, Viking Therapeutics unveiled early data from the first-in-human study of its investigational oral obesity drug VK2735, touting strong weight loss in healthy adults and an encouraging safety profile.
