NOVO — Semaglutide FDA Review (NDA213051, ORIG 1, 2019)
NOVO · 2019 · FDA Review (openFDA)
Report summary
This FDA review summarizes the clinical pharmacology of Novo Nordisk's oral semaglutide (Rybelsus) for type 2 diabetes. The drug, administered on an empty stomach, utilizes the absorption enhancer SNAC. The comprehensive development program, including 32 studies, established its pharmacokinetics, dose-response for HbA1c reduction, and safety profile. Semaglutide exhibits dose-proportional kinetics, a weekly half-life, and significant accumulation. While bioavailability varies, dose adjustment for weight is unnecessary. Exposure-response models confirm HbA1c reduction and link nausea/vomiting to dose titration. Immunogenicity rates were low with no impact on efficacy. Intrinsic factors and drug interactions were also assessed.
Key findings — cited to the page
| Proposed Indication | Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus | · p.2 |
| Applicant | Novo Nordisk | · p.2 |
| Associated IND | IND-114464 | · p.2 |
| Semaglutide sequence homology to human GLP-1 | 94 % | · p.8 |
| Recommended starting dose | 3 mg once daily | · p.9 |
| Dose increase after 1 month | 7 mg once daily | · p.9 |
| Maximum dose | 14 mg once daily | · p.9 |
| HbA1c change from baseline ED50 | 6 mg | · p.9 |
| Mean population-PK estimated steady-state concentration (7mg) | 6.7 nmol/L | · p.10 |
| Mean population-PK estimated steady-state concentration (14mg) | 14.6 nmol/L | · p.10 |
| Absolute bioavailability of semaglutide | 0.4 - 1 % | · p.10 |
| Route of Administration | Oral | · p.2 |
Source: NOVO ↗ · License: US Government public domain. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Metabolic library →