GLP-1 agonists have been shown to be beneficial in a lengthening list of diseases, but it seems Alzheimer’s disease may not be among them.
Novo Nordisk has just released the topline findings from two eagerly anticipated phase 3 trials of its oral formulation of GLP-1 drug semaglutide, with the deeply disappointing news that the drug was unable to slow down the progression of cognitive decline in patients with early-stage, symptomatic Alzheimer’s.
The evoke and evoke+ studies compared oral semaglutide to placebo in more than 3,800 subjects, but found that the GLP-1 wasn’t significantly better at slowing down progression of Alzheimer’s, as measured by the change from baseline in the widely used CDR-SB scale, despite promising results on other disease-related plasma biomarkers.
Novo Nordisk’s decision to run the phase 3 programme was prompted in part by the midstage ELAD trial of its older, once-daily injectable GLP-1 drug liraglutide – which suggested that the drug was able to reduce shrinking in the areas of the brain that control memory, learning, language, and decision-making – along with “real-world evidence studies, pre-clinical models, [and] post-hoc analyses from diabetes and obesity trials,” said the company.
While the data from the studies isn’t ready to be released, there seems to be little hope for the programme, as Novo Nordisk has already said it will discontinue a one-year extension period in the two studies.
The dose of oral semaglutide used in evoke and evoke+ is the same as that used in its already-approved Rybelsus formulation of oral semaglutide for type 2 diabetes, i.e. 14 mg once daily. That is lower than the 25 mg formulation that has been submitted for approval in the US as a weight-loss therapy, with a decision by the FDA expected shortly.
In a statement, Novo Nordisk’s R&D chief, Martin Holst Lange, said that the company felt that it had a responsibility to explore semaglutide’s potential in Alzheimer’s, despite “a low likelihood of success.”
He added: “We are proud to have conducted two well-controlled phase 3 trials in Alzheimer’s disease that meet the highest standards of research and rigorous methodology.”
Preliminary data from the two studies will be reported at the Clinical Trials in Alzheimer’s Disease (CTAD) conference in San Diego on 3rd December, with a full presentation scheduled for the Alzheimer’s and Parkinson’s Diseases Conferences (AD/PD) in Copenhagen next March.
Eli Lilly has previously said it was considering running trials of its dual GLP-1/GIP drug tirzepatide in Alzheimer’s, but does not have any studies on the go.
Shares in Novo Nordisk – already depressed by slowing growth for its semaglutide products in indications like type 2 diabetes and obesity – were down almost 10% at the time of writing.
It is the second disappointing result in Alzheimer’s in swift succession, coming after Johnson & Johnson abandoned a phase 3 clinical trial of its tau inhibitor posdinemab.
