Novo Nordisk splashes out as oral semaglutide starts phase III

Novo Nordisk's semaglutide, which could be the first oral alternative to injectable GLP-1 agonists in type 2 diabetes, has started phase III trials.

If it reaches the market, the oral formulation could have a massive impact on the GLP-1 agonist category, currently headed by Novo's own $2 billion-a-year Victoza (liraglutide) brand which stands alongside other drugs such as AstraZeneca's Bydureon (exenatide), GlaxoSmithKline's Tanzeum/Eperzan (albiglutide) and Eli Lilly's Trulicity (dulaglutide).

Semaglutide is also being developed as a once-weekly injection that has already been shown to provide good control of blood glucose in phase III trials, with a low risk of low blood sugar and beneficial effects on weight and appetite.

The new oral formulation has been developed with the help of Emisphere Technologies, and specifically its Eligen drug delivery technology, which attaches carrier molecules to the protein that allow it to be transported more readily across the lining of the gastrointestinal tract.

In phase II trials reported in February, oral semaglutide (also known as OG217SC) was found to be equivalent to the once-weekly injection of the drug in terms of its ability to reduce haemoglobin A1c levels (HbA1c), a measure of glucose control over time.

The phase III programme, called PIONEER, will consist of seven studies involving around 8,000 patients and will include a trial specifically looking at whether the drug can reduce cardiovascular disease in diabetics.

The first trial will compare a once-daily oral dose of semaglutide with Merck & Co's oral DPP-4 inhibitor Januvia (sitagliptin) and is scheduled to get underway early next year.

Novo is leaving nothing to chance as it advances semaglutide and other drugs in its diabetes portfolio, announcing a $2 billion investment programme over the next five years that will boost its production capacity with the construction of two new facilities in the US and Denmark.

One of these, at Clayton in North Carolina, will focus on producing active pharmaceutical ingredients (APIs) for isemaglutide and other diabetes drugs, while the Danish plant in Måløv will be used for 'tableting and packaging of oral semaglutide and future oral products'.

Both are due to come online in 2020, with the US facility employing 700 workers and the Danish plant employing 100.

"Delivering protein-based medicine like semaglutide in the form of a tablet and producing it on a large scale is a major challenge," said Mads Krogsgaard Thomsen, Novo's chief science officer.

"We are excited about the opportunities oral semaglutide represents as a new oral anti-diabetic agent to further improve type 2 diabetes treatment," he added.

Analysts seem to share that excitement, with a number suggesting oral semaglutide – while still a risky project – could be the biggest driver for growth at Novo in the next few years, ahead of other new products such as obesity drug Saxenda (liraglutide).

Meanwhile, the start of phase III trials of oral semaglutide is also a boost for Novo after it published disappointing results from a trial of Victoza in type 1 diabetes this week, revealing that it put patients at increased risk of low blood sugar episodes when given alongside insulin.