NN 9535 (semaglutide) meets endpoints for type 2 diabetes in phase III trial- Novo Nordisk

Novo Nordisk announced the headline results from SUSTAIN1, the first Phase IIIa trial for NN 9535 (semaglutide), the GLP-1 analogue administered once-weekly for Type 2 Diabetes. The trial investigated the efficacy and safety of 0.5 mg and 1.0 mg semaglutide as monotherapy during 30 weeks of treatment compared with placebo in 388 people with type 2 diabetes previously on diet and exercise.

The trial achieved its primary objective by demonstrating that from a mean baseline HbA1c of 8.1%, people treated with doses of 0.5 mg and 1.0 mg semaglutide, achieved superior improvements in HbA1c of 1.5% and 1.6%, respectively, compared to no change in HbA1c in the placebo group. 74% and 73% of the people treated with 0.5 mg and 1.0 mg semaglutide, respectively, achieved the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) treatment target of HbA1c below 7% compared with 25% of the people treated with placebo. Furthermore, from a mean baseline of 92 kg, people treated with semaglutide in both doses of 0.5 mg and 1.0 mg experienced a superior weight loss of 3.8 kg and 4.6 kg, respectively, compared with a weight loss of 1.0 kg for people treated with placebo.

In the trial, semaglutide appeared to have a safe and well-tolerated profile. The most common adverse events were related to the gastrointestinal system, primarily nausea, were comparable to liraglutide (Victoza) in similar trials and diminished over time. The discontinuation rates due to all adverse events for 0.5 mg and 1.0 mg semaglutide were 6% and 5% compared to a discontinuation rate of 2% for placebo.

Comment: In 2014, the FDA and EU gave approval for the once-weekly Trulicity (dulaglutide), from Eli Lilly, the only contender that has measured up to Victoza in a Phase III trial. It will also compete with AstraZeneca’s once-weekly GLP-1 receptor agonist Bydureon (extended-release exenatide), and GlaxoSmithKline’s Eperzan (albiglutide), approved in March 2014, amongst others. GLP-1 agonists are not risk free, however. Gastrointestinal side effects such as nausea, vomiting and diarrhoea seem to be associated with the treatment, and according to a study published in JAMA in 2013, Byetta may double patients' risk of pancreatitis. Claims that GLP-1 agonists as a class increase the risk of pancreatitis are still under investigation. Meanwhile liraglutide causes thyroid C-cell tumours at clinically relevant exposures in rodents, though this has not been confirmed in humans. The FDA and EMA continue to review whether these drugs increase the risk of pancreatitis and pancreatic cancer.