In good news for those averse to injections, GLP-1 agonist medication is a step closer to being offered in oral pill form, with AstraZeneca revealing "encouraging data" out of its Phase I study of its obesity and diabetes drug AZD5004.
In a presentation at the ObesityWeek conference in San Antonio this week, the UK pharmaceutical company perhaps best known in recent times for its COVID-19 vaccine, said AZD5004 performed similarly to injected GLP-1 agonists in the early-stage trial, and is now being assessed in two Phase IIb studies, with results scheduled for as soon as late 2025.
Much like current medications that need to be injected, the oral GLP-1 agonist is AstraZeneca's big hope in entering the lucrative obesity drug market and joining the likes of Novo Nordisk, the Danish company behind the semaglutide products Ozempic for diabetes and Wegovy for obesity.
In the Phase I trial, which tested AZD5004 on 72 healthy non-obese patients or people with type 2 diabetes, the drug was deemed safe in doses under 50 mg. Higher doses saw an increase in adverse gastrointestinal issues – in line with the side effects most reported in the drugs currently on the market. The people in the trial had an average weight loss of 5.8% after four weeks and saw improvements in their fasting plasma glucose.
Now, the drug will enter a dedicated obesity Phase IIb trial (the Vista study), as well as one specifically for type 2 diabetes (the Solstice study), no doubt to, like Novo Nordisk, hopefully emerge with two specific GLP-1 agonist medications. The obesity trial is expected to enroll 304 people and conclude towards the end of 2025. The Solstice study, with 384 patients, is expected to continue through to early 2026.
AstraZeneca licensed AZD5004 from Chinese company Eccogene in 2023 for nearly US$2 million, but anticipates that, if all goes to plan with the next stage, it could see $800 million in sales by 2032.
"We believe this oral GLP-1RA molecule could offer alternatives to current injectable therapies both as a potential monotherapy as well as in combination for cardiometabolic diseases such as type 2 diabetes, as well as for obesity," executive vice president Sharon Barr said last year when the deal with Eccogene was struck.
While the company's presentation at the conference was light on detail, it revealed that AZD5004 would be a once-daily small-molecule drug. It also revealed plans for another study that combines this drug with AZD6234, a long-acting analogue targeting the pancreas hormone amylin, which is currently in a Phase IIb weight loss trial. The company hopes a combination of the two will result is more targeted and effective fat loss.
At the conference, Barr didn't reveal a timeline for this two-drug trial, but said "encouraging Phase I data provided confidence for the combination strategy."
Tested for safety and tolerability, AZD5004 – which was taken with and without food – reportedly resulted in no serious side effects.
"We saw a dose-dependent increase in nausea and vomiting consistent with molecules in this class," Barr said at a briefing.
AstraZeneca is a few years behind Novo Nordisk and Eli Lilly, however, demand for their obesity drugs suggests there's plenty of room in the market for more players – especially for oral medications.
Viking Therapeutics also presented early-stage results from a trial of its own oral obesity candidate. The company reported its dual GLP-1/GIP co-agonist drug VK2735 saw up to an average of 8.2% weight loss over 28 days on its highest-tested dose of 100 mg.
Sources: AstraZeneca, ObesityWeek, Viking Therapeutics
