Novo Nordisk's amycretin shows competitive phase 2 weight loss

Just one day after two closely watched studies failed to show that Novo Nordisk's oral GLP-1 semaglutide slows the progression of Alzheimer's disease, the company reported encouraging phase 2 results for its next-generation weight-loss drug, amycretin.

This announcement lifted Novo Nordisk's stock by more than 4% today, partially recovering from yesterday's 12% drop.

Amycretin was tested in individuals with type 2 diabetes for the first time in this trial. The study enrolled over 440 individuals who continued to have elevated blood sugar levels despite use of standard medications like metformin, either with or without an SGLT2 inhibitor.

In the combined multiple-ascending-dose study, the drug's safety and efficacy were evaluated over a 36-week period using six weekly injectable doses (0.4-40 mg) and three daily oral doses (6, 25 and 50 mg).

The mid-stage data shows that daily oral amycretin achieved a placebo-adjusted weight loss of 7.6%, while the weekly subcutaneous formulation delivered 11.9%.

Oral amycretin users lost up to about 22 pounds (10.1%) from an average starting weight of about 223 pounds, while placebo users lost about 6 pounds (2.5%). Individuals who began at roughly 219 pounds and took the injectable form of amycretin lost up to 32 pounds (14.5%), while those who took a placebo lost about 6 pounds (2.6%).

By week 36, participants had not yet reached a weight-loss plateau at the higher doses, whether administered as an injection or a pill, the company says.

HbA1c, a measure of blood glucose, was also included in the readout. By week 36, the oral form of amycretin resulted in a 1.1% placebo-adjusted drop in HbA1c, whereas subcutaneous amycretin reduced it by 1.6%.

Improvements in glucose concentrations were dose-dependent for both drug formulations, the study found.

"We are very encouraged by the phase 2 data with amycretin in people with type 2 diabetes. The data further validate the potential best-in-class profile of amycretin" Martin Holst Lange, chief scientific officer and executive vice president of Research and Development at Novo Nordisk, said in the announcement.

Amycretin targets the GLP-1 pathway, similar to Novo Nordisk's blockbuster obesity drug Wegovy (semaglutide), while activating amylin receptors. This dual strategy is intended to trigger superior weight loss without the same degree of tolerability issues associated with commonly used GLP-1s.

Although Novo said that both formulations "appeared to have a safe and well-tolerated profile, consistent with other incretin and amylin-based therapies," tolerability data is limited, with the majority of adverse events being mild to moderate gastrointestinal symptoms.

Bolstered by the readout, Novo said it plans to move both oral and injectable versions of amycretin into late-stage trials in the first half of next year.

The Danish drugmaker trails its competitor Eli Lilly, which plans to move its selective amylin agonist eloralintide into phase 3 next month following mid-stage data reporting a 19.6% placebo-adjusted weight loss for the highest dose in people without type 2 diabetes.

Instead, amycretin may offer a differentiated profile, positioning it as a competitive option against Lilly's orforglipron and tirzepatide.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.