- Novo Nordisk plans to test whether its diabetes pill Rybelsus can prevent dementia in Alzheimer's, announcing Wednesday a plan to begin a Phase 3 trial next year in 3,700 people with early-stage disease.
- Novo made the decision after combing through clinical data and evidence since the drug's launch suggesting that Rybelsus patients appear to have a lower risk of developing dementia. Its announcement comes as the need for an effective Alzheimer's treatment remains unmet: the Food and Drug Administration may be pressured to reject the latest Alzheimer's hopeful, Biogen's aducanumab, after negative feedback from an advisory panel.
- Alzheimer's drug development is notoriously fraught, with numerous failures in spite of billions of dollars spent on research — the latest example being azeliragon, an experimental treatment from vTv Therapeutics. Novo's trial, however, represents a fairly low-risk bet, as Rybelsus is an approved drug already generating sales revenue in diabetes and can bypass early-stage safety studies.
Denmark-based Novo is known primarily for its work in diabetes and metabolic disease, having a suite of insulins and drugs like Rybelsus, called GLP-1 agonists. Taking on neurodegeneration, then, marks a strategic departure, albeit one with high reward, given the dearth of effective Alzheimer's medicines.
Novo's decision to move forward with this trial is founded on intriguing, but tentative, research. Retrospective analyses of the large cardiovascular outcomes trials of Rybelsus and two other, similar Novo drugs found that of nearly 16,000 diabetics followed for more than three years, 32 patients taking a placebo and 15 taking a GLP-1 drug developed dementia.
That 52% risk reduction, Novo said, is supported by Danish registries, U.S. claims databases and the FDA's adverse events reporting system, which have found similar associations.
Rybelsus and other GLP-1s may work by reducing levels of nervous system inflammation and therefore help people from developing the memory and critical thinking problems characteristic of Alzheimer's. Diabetes itself is a risk factor for dementia, so disease control may help, too.
The trial will enroll patients with mild cognitive impairment or mild dementia, and track their disease progression. Novo expects participants to be tracked for two years.
Novo's chief rival, Eli Lilly — which is developing eight experimental Alzheimer's and dementia drugs — is almost certainly aware of the data hinting at the promise of GLP-1 drugs in treating the memory-robbing disorder. Earlier this year, some of its employees were listed as authors on a review of large studies of Lilly's diabetes drug Trulicity, which found the treatment reduced the risk of cognitive decline by 14%.
For now, Lilly hasn't yet taken the same leap as Novo. It is focusing its efforts on the more established hypotheses in Alzheimer's, which suggests the root cause of the disease is the buildup of brain plaques consisting of two proteins, called amyloid beta and tau.