Corxel's Oral GLP-1 Agonist CX11 Achieves Up to 11.5% Weight Loss in U.S. Phase 2 Obesity Trial
核心洞察
Corxel Pharmaceuticals (搜索) reported positive top-line results from its U.S. Phase 2 trial of CX11, an oral small molecule GLP-1 receptor (搜索) agonist, in obese and overweight (搜索) adults.
CX11 achieved up to 11.5% weight loss at 36 weeks, with weight reduction continuing at a consistent rate and no evidence of a slowing trajectory.
The treatment demonstrated a favorable gastrointestinal tolerability and safety profile, with a low 5.0% discontinuation rate due to GI adverse events and no hepatic safety signal.
Corxel Pharmaceuticals (搜索) Limited announced positive top-line results from its Phase 2 trial evaluating CX11, an oral small molecule GLP-1 receptor (搜索) agonist (GLP-1 RA), in obese and overweight (搜索) participants in the United States. The trial met its primary endpoints, with CX11 achieving up to 11.5% weight loss at 36 weeks, showing continued weight reduction at a consistent rate and no evidence of a slowing trajectory. Building on these results and the successful China obesity (搜索) Phase 3 results recently announced by its partner Vincentage Pharma (搜索) Co., Ltd., Corxel plans to advance into pivotal global Phase 3 studies of CX11 in weight management.
Trial Design and Patient Population
The Phase 2 trial (NCT07011797) enrolled 246 adults in the United States with obesity (搜索) (BMI ≥30 kg/m²) or who were overweight (搜索) (27 kg/m² ≤ BMI <30 kg/m²) with at least one weight-related comorbidity. Participants were randomized 1:1:1:1:1 to receive CX11 120 mg, CX11 160 mg, CX11 200 mg (slow titration), CX11 200 mg (fast titration), or placebo once daily for 36 weeks.
At 36 weeks, CX11 achieved up to 11.5% weight loss among U.S. obesity (搜索) patients, with weight loss continuing at a consistent rate and no evidence of a slowing trajectory. The point estimate is important, but so is the direction of the response. Weight reduction was continuing at a consistent rate when the study ended, with no evidence that it had reached a plateau.
Safety and Tolerability Profile
Throughout the 36-week double-blind treatment period, CX11 demonstrated a favorable gastrointestinal (GI) tolerability and safety profile. Nausea rates ranged from 33-34%, vomiting from 12-16%, diarrhea from 4-12%, and constipation from 2-12% across different dosing cohorts. The most commonly reported adverse events were GI-related and generally mild to moderate in severity. There were no severe cases of nausea, vomiting, diarrhea, or constipation reported in the study.
Gastrointestinal adverse events (GI AEs) primarily occurred during the dose escalation period and gradually subsided during the maintenance period. The overall treatment discontinuation rate due to GI AEs was low, at 5.0%. CX11 continued to demonstrate a favorable hepatic safety profile in the study, with no hepatic safety signal observed. To date, more than 1,500 participants have been studied across all CX11 clinical studies, with no hepatic safety signal identified.
"We are delighted with these positive U.S. Phase 2 results, which are consistent with the competitive profile established in the China Phase 3 program," said Bo Liang, MD, PhD, Chief Medical Officer of Corxel. "Together, these datasets reinforce our confidence in CX11 and our conviction to offer patients around the world an effective and highly tolerable option with dosing flexibility."
Complementary Evidence from the China Phase 3 Program
Vincentage's pivotal Phase 3 trial enrolled 840 adults in China with obesity (搜索), or who were overweight (搜索) and had at least one weight-related comorbidity. After 52 weeks, mean body weight declined by 12.2% with the 120 mg dose and 12.4% with the 160 mg dose, compared with 1.3% for placebo. Gastrointestinal events were generally mild to moderate and occurred primarily during dose escalation. No severe nausea or vomiting was reported, discontinuation due to treatment-related adverse events was 1.8% in each active-treatment group, and no hepatic safety signal was observed. Based on this data, Vincentage has just submitted an NDA for weight management in China.
The importance of the China program and Corxel's global program is that they provide complementary evidence across geographies and study designs.
Addressing Unmet Needs in Cardiometabolic Disease
Cardiometabolic disease remains a leading cause of death, responsible for over 30% of global annual mortality. Medication adherence remains a critical barrier, with studies showing up to 50% of patients with chronic conditions do not take medications as prescribed. Broad adoption of current GLP-1 therapies remains suboptimal due to challenges such as inconvenience of subcutaneous injections, titration difficulty, limited tolerability, and supply constraints.
CX11 is designed as a once-daily oral treatment without food or water restrictions or a fixed dosing-time requirement. It does not require refrigeration or light-protected storage. Its small molecule profile may also support more cost-efficient and scalable manufacturing and distribution.
Dosing Flexibility and Next Steps
Dosing flexibility matters because the early treatment experience can influence whether someone remains on a long-term therapy. Patients may respond differently to the pace of escalation and to different dose levels. Giving physicians the ability to consider both clinical response and tolerability may help them manage treatment more effectively than a rigid, one-size-fits-all approach. The Phase 2 study included both slow and fast titration approaches at the 200 mg dose specifically to generate information that can inform later-stage regimen design.
Corxel acquired worldwide development and commercialization rights outside Greater China to VCT220, now CX11, in December 2024. Vincentage continues to lead the program in Greater China, while Corxel is responsible for advancing it across the rest of the world. Corxel plans to advance CX11 into a global Phase 3 clinical trial for weight management.
Beyond CX11, Corxel's cardiometabolic portfolio includes JX10, a thrombolytic and anti-inflammatory agent for acute ischemic stroke now in a global Phase 2/3 trial, and CX12 (搜索), an internally discovered oral small molecule amylin receptor (搜索) agonist in preclinical development. CX12 reflects the view that the next phase of obesity (搜索) treatment will involve multiple complementary biological pathways to bring additional clinical benefits beyond GLP-1 RA.