GLP-1RA

GLP-1RA Alzheimer’s hopes dashed after Novo Nordisk’s semaglutide miss

While the Phase III results confirm prior analyst sentiments, a KOL notes that GLP-1RAs could still show potential in the preventive Alzheimer’s setting.

Novo Nordisk’s Rybelsus (oral semaglutide) has failed to demonstrate efficacy in a late-stage trial in Alzheimer’s disease, denting hopes of glucagon-like peptide-1 receptor agonists (GLP-1RAs) offering patients new treatment options.

During the Phase III EVOKE (NCT04777396) and EVOKE+ (NCT04777409) studies, the type 2 diabetes pill, which has the same active ingredient as star weight loss drug Wegovy (semaglutide), did not significantly slow Alzheimer’s progression compared with placebo after two years of treatments.

This was evidenced by Rybelsus’ inability to exhibit a significant change in clinical dementia rating, sum of boxes (CDR-SB) scores from baseline. Despite having no significant impact on disease progression, once-daily treatment with Rybelsus did trigger improvements in Alzheimer’s disease-related biomarkers.

However, it seems that biomarker changes alone were not enough to keep the drug in development within Alzheimer’s disease, as Novo Nordisk is now discontinuing the one-year extension periods for both the EVOKE and EVOKE+ trials.

While Novo Nordisk’s next steps in Alzheimer’s remain unclear, investors have shown their sentiments towards the readout, as the pharma company’s stock dropped 5.8% from DKK 304.65 ($46.90) at market close on 21 November to DKK 287.00 at market close on 24 November. The company’s market cap currently sits at DKK 1.24tr ($191.32bn).

Novo Nordisk is not the only company to run into a roadblock in Alzheimer’s disease as of late, as Johnson & Johnson (J&J) announced it was discontinuing the AuTonomy study (NCT04619420) of posdinemab in the indication on 21 November. In the Phase II trial, the tau binder failed to significantly slow decline in early-stage patients.