Huadong Medicine's oral GLP-1 drug HDM1002 meets Phase III weight loss endpoints

September 27 — Huadong Medicine (hereinafter "the Company") announced that its independently developed Class 1 innovative drug, HDM1002, has met all primary and key secondary endpoints at Week 44 in a Phase III clinical trial, with further weight reduction observed at Week 52 and no plateau in weight loss. The drug also demonstrated multiple differentiated advantages, including improvements in several cardiometabolic markers, reductions in liver fat content and improvements in liver enzyme indicators, as well as preferential fat loss with preservation of lean body mass. The Company has completed a Pre-NDA (New Drug Application pre-submission meeting) communication and is about to formally submit a marketing application in China for HDM1002 tablets for weight management.

Phase III Trial Design

According to the announcement, the HDM1002-301 study was a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial. It enrolled 857 adult patients who were either obese (BMI ≥ 28 kg/m²) or overweight (BMI ≥ 24 kg/m²) with at least one weight-related comorbidity. Participants were randomized in a 2:2:1 ratio to receive either HDM1002 200 mg once daily, HDM1002 400 mg once daily, or placebo, over a 52-week treatment period.

• Mean baseline body weight: 83.6 kg
• Mean baseline BMI: 30.7 kg/m²
• Female participants: 66.5%

The primary endpoints were the percentage change in body weight from baseline at Week 44, and the proportion of participants achieving a weight reduction of ≥ 5% from baseline.

Weight Loss Efficacy

At Week 44, the HDM1002 200 mg QD and 400 mg QD groups achieved mean weight reductions of 9.2% and 10.7% from baseline, respectively, compared to 1.5% in the placebo group. At Week 52, the two dose groups achieved mean reductions of 10.7% and 12.2%, respectively, versus 1.2% for placebo.

Weight Loss Achievement Rates at Week 52

| Criterion | HDM1002 200 mg QD | HDM1002 400 mg QD | Placebo | |-----------|-------------------|-------------------|---------| | ≥ 5% weight loss | 74.6% | 79.6% | 18.3% | | ≥ 10% weight loss | 46.7% | 53.9% | 6.4% | | ≥ 15% weight loss | 21.1% | 29.1% | 2.8% |

All results in the treatment groups were significantly superior to placebo.

Differentiated Profile: Fat Loss with Muscle Preservation

Notably, HDM1002 demonstrated a "fat-reducing, muscle-preserving" profile, achieving weight loss primarily through reduction of adipose tissue while retaining lean body mass. The drug also showed potential therapeutic value for metabolic dysfunction-associated steatotic liver disease / metabolic-associated steatohepatitis (MASLD/MASH).

Safety and Tolerability

The overall safety profile of HDM1002 was favorable and consistent with the known safety characteristics of GLP-1 receptor agonists.

Oral Formulation Advantage

Currently, mainstream GLP-1 drugs are predominantly injectable formulations, which present challenges such as injection pain, cold chain transportation requirements, and needle aversion in some patients. Oral formulations are considered a key direction for improving medication accessibility. To date, the only oral small-molecule GLP-1 receptor agonist approved globally is Eli Lilly's product.

HDM1002 is positioned to fill this gap. As a small-molecule oral formulation taken once daily, its absorption is unaffected by food or water intake, allowing flexible administration. This regimen, closer to that of conventional chronic disease medications, is expected to reduce patient discontinuation rates and improve long-term treatment adherence.

Huadong Medicine's GLP-1 Pipeline Strategy

Huadong Medicine is both a pioneer in GLP-1 biosimilars and an innovator in domestic GLP-1 novel drugs, advancing its endocrinology and metabolic disease portfolio through a differentiated pipeline matrix.

• Liluping® (liraglutide injection) was approved in 2023 as the first domestic liraglutide biosimilar and the first GLP-1 product approved in China for obesity or overweight indications.
• The Company's semaglutide injection has had its marketing applications accepted in China for both diabetes and weight management indications, placing it in the domestic first tier.

The "Three Musketeers" in Metabolism

Beyond HDM1002, Huadong Medicine has built a comprehensive and differentiated pipeline of long-acting and multi-target global innovative drugs targeting GLP-1 and other metabolic regulatory pathways, including oral tablets and injectables. Two other candidates have entered the pivotal Phase III stage:

1. HDM1005 (poterepatide) — A GLP-1R/GIPR dual-target long-acting peptide agonist injection. The Company expects to submit a Pre-NDA communication application in Q4 2026.

1. DR10624 — Developed by Huadong Medicine's controlled subsidiary, Zhejiang Doer Biologics Co., Ltd., targeting FGF21R/GCGR/GLP-1R. It has received CDE Breakthrough Therapy designation for severe hypertriglyceridemia (sHTG) and has initiated a Phase III clinical study. A Phase II study for metabolic-associated fatty liver disease with high risk of liver fibrosis has yielded top-line results. The drug has also been selected for the National Major Science and Technology Project for Innovative Drug Development under the "Heart Failure Innovative Drug Development" program.

Differentiation Strategy

• HDM1002: Once-daily oral small molecule, single-target; differentiation lies in dosing convenience and fat-reducing/muscle-preserving effects.
• HDM1005: GLP-1R/GIPR dual-target long-acting peptide injection; differentiation lies in weight loss potency and dosing interval.
• DR10624: Differentiation lies in targeting severe hypertriglyceridemia and metabolic-associated fatty liver disease complications.

Full-Chain Capabilities

Huadong Medicine possesses end-to-end closed-loop capabilities spanning drug discovery, clinical development, regulatory filing, manufacturing, market access, and academic promotion. With decades of深耕 in endocrinology, the Company has a mature academic promotion team and terminal resources. On the manufacturing front, the Company has the capacity for active pharmaceutical ingredient (API) production.

In the GLP-1 field, leveraging its comprehensive pipeline, commercialization experience from marketed products, and cost control from in-house production capabilities, Huadong Medicine is well-positioned to secure a leading position among domestic players.

(Source: Securities Daily)