Novo Nordisk's oral formulation of semaglutide met its primary end point in a Phase II trial, suggesting changes could be coming for the increasingly crowded antidiabetic glucagon-like peptide 1 (GLP1) drug class.

The US Food and Drug Administration approved AstraZeneca's first-in-class GLP1 analogue exenatide for type 2 diabetes in 2005. The class has since grown with the approval of once-daily and once-weekly formulations of the therapies, which enhance insulin secretion. The market for GLP1-receptor agonists was worth US$3 billion in 2014, and is set to grow to $9 billion by 2023, according to Decision Resources. Novo Nordisk now seems to have cracked the oral delivery of these peptide therapeutics, and hopes it may be able to grow and dominate the market with an oral formulation of semaglutide. The company is also developing a once-weekly subcutaneous formulation of semaglutide.

In the 600-patient Phase II trial, glycated haemoglobin (HbA1c) levels improved by 0.7–1.9% in patients treated with different doses of the oral GLP1 analogue. HbA1c levels improved by 1.9% in a subcutaneous semaglutide comparator arm, and by 0.3% in a placebo comparator arm. Weight loss with the highest oral dose of semaglutide was comparable to weight loss with injected semaglutide.

Novo Nordisk is now considering its options for Phase III trials of their oral antidiabetic. The data suggest, however, that they may need 300-fold the amount of active ingredient to succeed with their oral drug (it is dosed at 40 mg per day for oral treatment, versus 1 mg per week for subcutaneous treatment), leading to some concerns about the commercial viability of this oral approach.

TransTech Pharma also has an oral GLP1 agonist in Phase II trials. Its TTP054 is a small molecule, however, rather than a peptide.

Intarcia, meanwhile, is developing a matchstick-sized device that is inserted under the skin to slowly release exenatide over 6 or 12 months. Their device has already cleared two Phase III trials (Nature Biotech. 32, 1178; 2014).