AstraZeneca ends development of daily GLP-1/glucagon co-agonist cotadutide

AstraZeneca has terminated the programme for its daily injectable GLP-1/glucagon co-agonist cotadutide, saying it will instead shift focus to AZD9550, a weekly injectable drug in the same class, as well as on its broader non-alcoholic steatohepatitis (NASH) pipeline. "Important data and learnings from the cotadutide programme will help to inform the continuing AZD9550 programme, and substantiates our belief in a dual agonist approach of GLP-1 and glucagon to drive complementary metabolic and anti-fibrotic benefits through systemic, as well as direct liver effects," a company spokesperson told FirstWord.

Cotadutide was being tested in the Phase IIb/III PROXYMO-ADV study of non-cirrhotic NASH patients with fibrosis. The trial, which started last year, is evaluating two once-daily subcutaneously administered doses of cotadutide versus placebo. PROXYMO-ADV remains under way although it is no longer recruiting, having topped off at 45 participants. It is expected to complete in April 2024. The AstraZeneca spokesperson said a readout of the study will depend on the number of subjects that remain in the programme after investigators consult with their patients.

Work in obesity, diabetes previously stopped

Following AstraZeneca's third-quarter financial results last year, Credit Suisse analysts noted that development of cotadutide had been halted in both obesity and diabetes. The analysts, citing company management, said that the decision was "driven by the product profile, given the high bar set by competition."

Meanwhile, cotadutide was also being tested in a pair of Phase I studies that have recently been terminated; one in patients with hepatic impairment and the other to assess the drug's effect on cardiac repolarisation in healthy participants. According to their respective entries on ClinicalTrials.gov, the studies were terminated based on "strategic pipeline considerations," and the decisions were "not due to any newly observed safety signals or a change in the risk/benefit profile."

AZD9550 heading to clinic

"We remain committed to addressing the needs of patients in the NASH space by aiming to deliver a diverse portfolio that addresses different disease drivers and stages of progression," the spokesperson said, adding that AZD9550 will be entering clinical studies this year.

Boehringer Ingelheim is also developing a dual-acting GLP-1/glucagon agonist in partnership with Zealand Pharma. The compound, dubbed BI 456906, is under investigation across Phase II trials, including for diabetes, obesity and NASH. A spokesperson for Boehringer Ingelheim told FirstWord that the company completed a mid-stage study comparing BI 456906 against placebo in people living with overweight/obesity without type 2 diabetes, and is planning to share results with the scientific community "in the coming months." Earlier data had shown up to 13.7% weight loss following 16 weeks of BI 456906 in a Phase Ib trial. "Boehringer Ingelheim is engaging in parallel with health authorities to discuss plans for Phase III trials for people living with overweight/obesity," the spokesperson said.