Novo Nordisk has lifted the lid on a phase 1 trial of its oral amylin and GLP-1 receptor co-agonist, linking the candidate to 13.1% weight loss after 12 weeks—and highlighting the potential for further reductions in longer trials.
The drug candidate is designed to act on GLP-1, the target of existing drugs such as Novo’s Ozempic and amylin. Because amylin affects glucose control and appetite, Novo posited that designing one molecule to engage both the peptide and GLP-1 could improve weight loss.
The phase 1 study is an early test of whether Novo can realize those benefits in an oral formulation.
Novo shared (PDF) a headline finding—13.1% weight loss after 12 weeks—in March but kept the rest of the dataset back for the European Association for the Study of Diabetes (EASD). At EASD Wednesday, the drugmaker said (PDF) it saw the 13.1% reduction in people who received 100 mg of amycretin once a day. The weight loss figures for the 50 mg and placebo groups were 10.4% and 1.1%, respectively.
Agnes Gasiorek, Ph.D., senior clinical pharmacology specialist at Novo, called the result “remarkable for an orally delivered biologic” in a presentation of the data at EASD. Average weight fell in both amycretin cohorts between the eighth and twelfth weeks of the trial, prompting Gasiorek to note that there were no apparent signs of plateauing while adding a caveat to assumptions that further weight loss is likely.
“It is important to consider that the relatively short treatment duration and limited time on final dose, being two weeks only, could potentially introduce bias to this observation,” the Novo researcher said. Gasiorek added that larger and longer studies are needed to fully assess the effects of amycretin.
The studies could clear up some of the outstanding questions about amycretin and how it compares to rival candidates in development at companies such as Eli Lilly, Pfizer, Roche, Terns Pharmaceuticals and Viking Therapeutics. The size of the trials and challenges of cross-trial comparisons make picking winners impossible at this stage but Novo looks competitive on efficacy.
Tolerability could be an issue, with 87.5% of people on the high dose of amycretin experiencing gastrointestinal adverse events. The result was driven by the percentages of people reporting nausea (75%) and vomiting (56.3%). Nausea cases were mild to moderate and patients who vomited did so once or twice, Gasiorek said.
Such gastrointestinal events are frequently seen in recipients of GLP-1 drugs but there are opportunities for companies to differentiate their assets based on tolerability. Viking, for example, reported lower rates of adverse events in the first part of its dose escalation study.