The Center for Drug Evaluation (CDE) in China has released a new set of Guidelines aimed at streamlining the design of clinical trials for semaglutide biosimilars, with a specific emphasis on weight management indications. These Guidelines are now open for public feedback for a period of one month, allowing stakeholders to contribute to the finalization of the document.
Semaglutide, a long-acting human glucagon-like peptide-1 (GLP-1) receptor agonist, was originally developed by Danish pharmaceutical company Novo Nordisk. It was approved in the US and European Union (EU) in 2017 under the trade name Ozempic for managing blood glucose levels in type 2 diabetes (T2D) patients. The drug gained market entry in China in April 2021. Later, in June 2021, the same molecule was approved in the US for weight loss under the trade name Wegovy, with this indication also registered in the EU and Japan.
In July 2023, the weight loss indication was updated to include a dosage regimen starting at 0.25mg for subcutaneous injection during the initial weeks, gradually increasing to 2.4mg from week 17 onwards.
According to the CDE, clinical studies for biosimilar versions of semaglutide must use the originator drug marketed in China as the reference. The CDE recommends a single-dose, randomized, parallel-controlled trial design. If indications for both T2D and weight management are filed concurrently, a single set of pharmacokinetic (PK) comparison research data can be utilized. The selection of sensitive doses capable of detecting PK differences between the experimental and reference drugs is advised. In PK comparison studies, a dosage of 0.25mg is recommended. Consistency in the choice of injection site is encouraged to facilitate sensitive evaluation of PK differences.
The Guidelines suggest that the study population should ideally consist of obese individuals without type 2 diabetes, with a BMI of ≥ 28.0kg/m², to minimize subject dropout during clinical trials. The primary evaluation indicator is the difference in relative baseline weight loss percentage between the experimental drug group and the originator reference group after 44 weeks of treatment. Secondary efficacy indicators may include the proportion of subjects with a relative weight loss of ≥ 5% from baseline and waist circumference indicators.
For pharmacokinetic studies, the CDE notes that since the absorption, metabolism, and clearance pathways of semaglutide are largely consistent across healthy subjects and obese/overweight patients, PK comparative studies in obese patients are not necessary.- Flcube.com
