Topline Phase 3 Results of Hengrui Pharma and Kailera Therapeutics’ Dual Agonist HRS9531 Shows Promising Weight Loss: A Rising Competitor to Zepbound?

In a key event, Chinese pharmaceutical giant Hengrui Pharma and U.S.-based biotech firm Kailera Therapeutics have reported inspiring Phase 3 results for their novel weight-loss drug candidate, HRS9531. This once-weekly injectable drug, a dual GLP-1/GIP receptor agonist, demonstrated weight reduction effects that match with its closest rival of Eli Lilly’s tirzepatide (Zepbound), showcasing it as a strong potential alternative in the anti-obesity therapeutics market.

The HRS9531 program was initiated by Hengrui Pharma and is based on a GLP-1 receptor agonist platform aimed at treating metabolic disorders. In 2023, Hengrui partnered with U.S.-based Kailera Therapeutics to advance the international development of HRS9531. This collaboration supports the global clinical progression of the drug in what is considered to be the most competitive field of GLP-1-based therapies.

Trial Design and Results

The HRS9531‑301 trial (NCT06396429) is a randomized, double-blind, placebo-controlled, multicenter Phase 3 clinical study conducted across multiple sites in China. The study was sponsored by Hengrui Pharma and evaluated the efficacy and safety of HRS9531. The trial spanned 48 weeks of treatment, with an additional follow-up period to monitor long-term effects and adverse events. The trial was designed in a way that it will support regulatory approval in China and other markets.

The study enrolled 567 adults aged more than 18 years with a mean weight of 93 kg with obesity or overweight status as defined by a BMI ≥28 kg/m² or a BMI ≥24 kg/m² with at least one obesity-related comorbidity (e.g., hypertension, dyslipidemia, sleep apnea).

Key exclusion criteria included a diagnosis of type 1 or type 2 diabetes, History of significant gastrointestinal disease, prior or ongoing anti-obesity pharmacotherapy or bariatric surgery, and uncontrolled psychiatric illness or endocrine disorders.

This strict inclusion-exclusion criterion was designed to isolate the weight-loss effect of HRS9531 in a non-diabetic population; the trial will mimic the real-world use cases for first-line obesity pharmacotherapy.

Participants were randomized to receive once-weekly subcutaneous injections of HRS9531 at 2 mg, 4 mg, or 6 mg, or Placebo. All participants followed a dose-escalation schedule during the early phase to improve gastrointestinal tolerability, followed by fixed-dose maintenance through week 48. Lifestyle advice was given to all groups (diet and physical activity guidelines), in line with global obesity trial standards (similar to SURMOUNT and STEP trials).

Primary Endpoint includes percent change in body weight from baseline to week 48; key secondary endpoints include the proportion of participants achieving ≥5%, ≥10%, ≥15%, and ≥20% weight loss. Absolute weight change (kg), Changes in waist circumference, BMI, metabolic biomarkers (lipid levels, liver enzymes, blood pressure), and Patient-reported outcomes (quality of life, satiety). These endpoints reflect a comprehensive and clinically meaningful set of outcomes that regulatory bodies typically require for obesity drug approvals.

HRS9531 showed robust and dose-dependent weight loss, with top-line data showing at a 6 mg dose a mean body weight reduction of 17.7% vs baseline, Placebo-adjusted difference of 14.1%, a 4 mg dose with 14.5% weight loss, and a 2 mg dose with 9.8% weight loss.

88.4% of participants in the 6 mg arm lost ≥5% body weight, 70.9% achieved ≥10%, 51.2% achieved ≥15%, and 44.2% achieved ≥20% weight loss

These efficacy results are comparable to or even exceed benchmarks seen with established drugs like semaglutide (Wegovy) and tirzepatide (Zepbound) in similar populations.