▎Edited by the WuXi AppTec content team

Today, the R&D team of Amgen (Amgen), Inc. in the subsidiary journal of "Nature"Nature MetabolismPublished the preclinical studies and Phase 1 clinical trial results of the investigational weight loss therapy AMG 133. The clinical trial results showed,Obese patients only need one injection per month. After 85 days of treatment with a high dose of AMG 133, their weight can be reduced by 14.5% (approximately 26 catties). Notably, these patients can still maintain a weight reduction of 11.2% after stopping the medication for 150 days.Amgen is conducting a Phase 2 clinical trial to explore maintaining weight loss in patients by using a lower dose of AMG 133 or less frequent dosing after their weight has been reduced with a higher dose of AMG 133.

▲AMG 133 is a GLP-1 receptor agonist and GIPR antagonist (Image source: Reference [2])

In Phase 1 clinical trials, obese participants received different doses of AMG 133. In the single ascending dose cohort, the dose of AMG 133 ranged from 21 mg to 840 mg. In the multiple ascending dose cohort, the dose of AMG 133 ranged from 140 mg to 420 mg, administered once every 30 days.

The test results showed that in the multi-dose escalation cohort, the patients' weight, BMI, and waist circumference all showed a dose-dependent decrease.Patients receiving AMG 133 at a dose of 420 mg experienced an average weight reduction of 14.5% (approximately 26 catties) from baseline at day 85.It is worth mentioning that patients who usually receive GLP-1 receptor agonist treatment often experience weight rebound after discontinuation of the medication, butPatients receiving high-dose AMG 133 treatment maintained weight loss of over 10% even 150 days after discontinuation., demonstrating the sustained efficacy of AMG 133.

▲In the multi-dose escalation cohort, patients' weight, BMI, and waist circumference all showed a dose-dependent decrease (Image source:Reference [2])

In terms of adverse events, the most common adverse events were gastrointestinal-related, including nausea and vomiting, most of which were mild, similar to those known for GLP-1 receptor agonists. No increase in the severity of nausea, vomiting, or other adverse events was observed with increasing doses of AMG 133.

In the ongoing Phase 2 clinical trial, researchers from Amgen will first titrate the dosage for participants, using the maximum tolerated dose of AMG 133 to induce weight loss. After a period of time, the dosing regimen will be transitioned to a lower-dose maintenance treatment plan to explore whether weight loss can be sustained at a lower dose. Dr. Narimon Honarpour, Vice President of Global Development at Amgen, stated in an interview with the industry media STAT,There may be an opportunity to use an induction maintenance strategy to formulate the dosing regimen for AMG 133, similar to the medication strategies of various anti-inflammatory drugs, where a high dose is used at the beginning of treatment and a low dose or reduced dosing frequency is applied during the maintenance phase.

▲Dr. Robert Gabbay, Chief Scientific Officer and Chief Medical Officer of the American Diabetes AssociationWuXi AppTec Global ForumShare Insights

Obesity, as a risk factor for various metabolic diseases such as diabetes, cardiovascular disease, and non-alcoholic steatohepatitis (NASH), is receiving increasing attention. The application of GLP-1 receptor agonists in the field of weight loss has brought profound impacts to the industry and further emphasized the significant value of disease prevention. Recently, Dr. Robert Gabbay, Chief Scientific Officer and Chief Medical Officer of the American Diabetes Association, stated in...WuXi AppTec Global ForumAs stated above,We should work together to build a "prevention-based world."For example, high-risk populations can be identified through biomarkers for disease prevention. Digital wearable devices can also help people understand their health data and make corresponding changes. We look forward to medical advancements that can prevent problems before they occur, allowing more people to lead healthy lives.

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