FDA Approves Novo Nordisk's Oral Semaglutide, First GLP-1 in Pill Form

FDA today approved oral semaglutide, to be sold as Rybelsus, the first glucagon-like peptide-1 (GLP-1) receptor agonist available in a pill form. Novo Nordisk, which previously received approval for injectable semaglutide (Ozempic), sought approval for the oral type 2 diabetes (T2D) therapy in March under a priority review process.

The filings are based on the PIONEER clinical trial program for oral semaglutide, which included a cardiovascular outcomes trial. Unlike the injectable form, which is given once a week, the oral form of semaglutide is taken once a day. Today’s approval does not address Novo Nordisk’s separate requests for cardiovascular (CV) indications for both formulations of semaglutide; those decisions are anticipated in January 2020.

Oral semaglutide is approved in 2 doses, 7 mg and 14 mg, which will be available in the fourth quarter of 2019, according to a sattement from Novo Nordisk.

The drug could address an unmet need in patients with T2D who are overweight, as the GLP-1 receptor agonist class has been shown to help patients achieve significant weight loss. However, not all patients are willing to use an injectable drug, even one only needed once a week.

"People living with type 2 diabetes deserve more innovation, research and support to help them achieve their individual [glycated hemoglobin] goals," Todd Hobbs, vice president and United States chief medical officer of Novo Nordisk, said in a statement. "With Rybelsus, we have the opportunity to expand use of effective GLP-1 receptor agonist therapy by providing adults with type 2 diabetes an oral medication which was previously only available as an injection to help with managing their blood sugar."

During a discussion at the American College of Cardiology Scientific Session this spring, panelists reviewed case studies on when to prescribe GLP-1 receptor agonists versus sodium-glucose cotransporter 2 (SGLT2) inhibitors; cardiologists said there are cases in which GLP-1 receptor agonists are indicated, but patients will not take an injectable drug.

Phase 3 data published in March in JAMA, based on a randomized clinical trial of 1864 adults, showed that those taking oral semaglutide at 7 mg per day or 14 mg per day with metformin, compared with sitagliptin, showed statistically significant reductions in glycated hemoglobin after 26 weeks. Reductions were —1.0% for 7 mg and —1.3% for 14 mg, respectively, compared with —0.8% for sitagliptin.

FDA’s decision comes a week after the Institute for Clinical and Economic Review (ICER) found in a draft report that assuming oral semaglutide is priced similarly to the injectable formulation, it would be less cost-effective than the SGLT2 inhibitor empagliflozin, sold as Jardiance by Eli Lilly and Boehringer Ingelheim. However, the authors cautioned they could not draw a final conclusion until the product was priced.

Oral semaglutide, the ICER authors wrote, would produce “incremental benefit” compared with other T2D treatments in terms of preventing heart attacks, strokes, and other major CV events. But, they continued, this is “only part of the treatment puzzle,” and other options may provide better treatment at a lower cost.

When contacted by The American Journal of Managed Care^® a spokesperson for Novo Nordisk said the company will respond to the draft ICER report at the end of October.