Novo Nordisk’s semaglutide, an oral GLP-1 analogue, continues to rack up positive Phase III clinical trial data compared to its competitors.
Novo Nordisk’s semaglutide, an oral GLP-1 analogue, continues to rack up positive Phase III clinical trial data compared to its competitors. The company reported the results of two Phase III trials, PIONEER 4, comparing semaglutide to its own Victoza (liraglutide injection) or placebo, and PIONEER 7, comparing semaglutide to Merck & Co.’s Januvia (sitagliptin).
Both trials used two distinct statistical approaches, one required by recent regulatory guidance that evaluates the effect of the drugs regardless of ending treatment and use of rescue medication. The other method describes the drugs’ effect while on treatment and without the use of rescue medication.
PIONEER 4 lasted a year and was a double-blinded, double-dummy trial evaluating 14 mg oral semaglutide compared to Victoza 1.8 mg and placebo in 711 people with type 2 diabetes that isn’t properly controlled by metformin, with or without an SGLT-2 inhibitor. It met its primary objective, showing a non-inferior reduction in HbA(1c) and statistically significant and superior weight loss at 26 weeks compared to Victoza.
PIONEER 7 also achieved its primary goal, showing that semaglutide was significant and superior to Januvia, and demonstrated significant and superior reductions in body weight versus Januvia.
Analysts with Deutsche Bank wrote in a note, “This data is important, as it positions oral-sema as at least as good as the market leading injectable GLP-1.” They also projected that it could eventually hit $5 billion in annual sales.
On May 30, Novo Nordisk reported that its PIONEER 2 trial, which evaluated oral semaglutide compared to Boehringer Ingelheim and Eli Lilly’s Jardiance (empagliflozin) in patients with type 2 diabetes. The trial showed semaglutide had a statistically significant and superior improvement in HBA1C compared to Jardiance at 26 weeks, but the difference in weight loss in the same period was not statistically significant in one data analysis method, while it was in another. At that time, Deutsche Bank analysts wrote, “Oral semaglutide increasingly appears to be on its way to become a major blockbuster. We believe this news should come as expected to most investors, a relief to some and a source of controversy to a few.”
The company hopes to launch the drug in 2020. There are six remaining clinical trials ongoing, with the PIONEER 3 trial expected to readout before the end of the second quarter. That trial is comparing three different dosages of oral semaglutide to Januvia.
GLP-1 agonists are a class of enzymes that help stimulate insulin production. They were originally discovered by John Eng while working in the laboratory of Rosalyn Yalow at the Mount Sinai School of Medicine. His research was on peptide hormones, and in the late 1980s he was advancing Yalow’s research by developing more sensitive tests to help identify hormones. He began with guinea pigs and then chinchillas. He was looking for more difficult test subjects, when he read about earlier work on snake venom and lizard venom, especially the venom of the Gila monster. In 1992, he identified two compounds in Gila monster venom, one which he named exendin-4. It was similar to GLP-1 and was eventually licensed to Amylin Pharmaceuticals to develop into Exenatide, the first GLIP-1 analogue, which was approved in the U.S. in 2005.
