Hengrui’s HRS9531 NDA Accepted in China, First Homegrown GLP-1/GIP Dual Agonist to Challenge Tirzepatide

On September 1, 2025, Jiangsu Hengrui Pharmaceuticals announced that China's National Medical Products Administration (NMPA) accepted the New Drug Application (NDA) for HRS9531 injection, developed by its subsidiary Fujian Shengdi Pharmaceutical [1]. This is the first homegrown GLP-1/GIP dual agonist entering regulatory review for obesity in China. Positioned as a once-weekly injectable for long-term weight management in adults with obesity (BMI ≥28 kg/m²) or overweight (BMI ≥24 kg/m²) with at least one weight-related comorbidity (e.g., hyperglycemia, hypertension, dyslipidemia, obstructive sleep apnea, or fatty liver), HRS9531 is a direct homegrown challenger to Eli Lilly’s tirzepatide (Zepbound/Mounjaro), the global benchmark in this class [1,2].

Significance of HRS9531’s NDA Acceptance

HRS9531’s filing signals China’s growing strength in the GLP-1/GIP space, addressing a critical need amid the nation’s obesity epidemic. Obesity, driven by genetic and environmental factors, increases risks for diabetes, cardiovascular diseases, cancers, musculoskeletal disorders, and mental health issues [3,4]. With over 140 million obese adults—over 15% of China’s population—and rising rates due to urbanization, healthcare systems face significant strain [4,5]. The Healthy China 2030 initiative, updated in April 2025, prioritizes affordable treatments [5]. HRS9531, with proprietary intellectual property, promises enhanced accessibility by reducing reliance on costly imports, potentially transforming chronic weight management while aligning with national health goals [1,6].

Clinical Data Highlights and Comparison with Tirzepatide

HRS9531’s Phase 3 trial (HRS9531-301), a multicenter, randomized, double-blind, placebo-controlled study, enrolled 567 Chinese adults with obesity or overweight (mean baseline weight ~93 kg) plus comorbidities, testing 2 mg, 4 mg, and 6 mg doses versus placebo over 48 weeks [7–10].

Key results:

• Efficacy: Mean weight loss reached 17.7% (placebo-adjusted 16.3%) in the primary analysis. In the high-dose 6 mg group, the supplementary analysis (hypothetical estimand) reached 19.2% mean weight loss (placebo-adjusted 17.7%), with 44.4% achieving ≥20% loss. [7,8,11,12].
• Additional Benefits: Improved blood pressure, glucose, triglycerides, and waist circumference; no plateau observed, suggesting potential for greater efficacy with longer use [10,13].
• Safety: Well-tolerated, with most adverse events mild-to-moderate and gastrointestinal, consistent with GLP-1 class effects [7,8,14].

Phase 2 data (8 mg, 36 weeks) showed up to 23.6% loss (placebo-adjusted 21.7%), without plateauing [13,15]. In comparison, Lilly’s tirzepatide in SURMOUNT-1 (72 weeks) achieved 15.0–20.9% loss (5–15 mg) versus 3.1% placebo [16], with 12.8–14.7% in SURMOUNT-2 (type 2 diabetes) [17], and up to 26.6% over 84 weeks in SURMOUNT-3 [18]. Tirzepatide outperformed semaglutide in SURMOUNT-5 (20.2% vs. 13.4%) [20].

HRS9531’s 19.2% at 48 weeks is achieved in just 48 weeks, while tirzepatide reached 20.9% only after 72 weeks — highlighting HRS9531’s potential to close the efficacy gap earlier in treatment. Safety and cardiometabolic benefits remain comparable [7,16,21].

Impact on China’s Market Landscape

China’s obesity drug market is projected to reach $517.7 million by 2030 at a 19% CAGR potentially hitting $7.5 billion with broader indications like MASH and CKD [22–24]. Valued at ~$1.7 billion for GLP-1s in diabetes and obesity, the sector is constrained by scarce domestic options and high import costs [25,26]. To illustrate the near-term and long-term market potential, the following table summarizes projections for China and globally:

HRS9531’s NDA could drive broader access through local manufacturing, aligning with biotech incentives and easing healthcare burdens [5,23,27].

Competitive Landscape

The GLP-1 arena in China is fiercely competitive, with over 60–70 late-stage candidates, predominantly GLP-1 derivatives or multi-agonists [28,29]. Multinationals lead: Lilly's tirzepatide (Mu Feng Da) was approved in July 2024 for weight management, posting $49.26 billion in global sales in 2024, with Q2 2025 at $33.81 billion [1,30]. Novo Nordisk's semaglutide (Wegovy) holds strong, but tirzepatide has overtaken it in sales.

Domestic rivals include Innovent Biologics' mazdutide (GCG/GLP-1 dual agonist), approved in June 2025 as the world's first in its class, showing 18–20% weight loss [31,32]; other players like Hangzhou Jiuyuan Gene Engineering, Huadong Medicine, and Gan & Lee Pharmaceuticals advance multi-target agents, emphasizing long-acting formulations and differentiation [28,33]. Hengrui's HRS9531, mirroring tirzepatide's mechanism, positions it for direct competition, potentially capturing 20% market share by 2033 via competitive pricing and sales networks [23,34]. Ex-China licensing to Kailera Therapeutics (up to $6 billion in milestones) signals global ambitions [6,35–37].

Emerging oral GLP-1s add another layer, with China leading in development amid global setbacks [50]. Over 25 oral candidates are progressing, including Hengrui's HRS-7535 (Phase 3, 9.5% weight loss in Phase 2), Huadong's HDM1002 (Phase 3), and Ascletis' ASC30 (Phase 2a). Global orals like Lilly's orforglipron (Phase 3 in China since 2023, 12.4% weight loss in ATTAIN-1, planning 2025–26 filings) and Novo's oral semaglutide (16.6% loss in OASIS 4, NDA submitted August 2025 for obesity dose) offer convenience but lower efficacy (12–16% vs. 20%+ for injectables) [2,8,15,50]. These could erode injectable market share through ease of use and affordability, though injectables like HRS9531 retain superiority in weight loss magnitude. Patent expiry for semaglutide in China (2026) will spur biosimilars, intensifying price competition.

Development Cost Comparison: HRS9531 vs. Tirzepatide

Hengrui has invested approximately 452.35 million RMB (~$63 million USD) in HRS9531's development, reflecting efficient R&D in China's cost-effective ecosystem [1,38]. In contrast, Lilly's tirzepatide involved massive outlays: over $9 billion in manufacturing expansions alone by 2024, plus costs for extensive global trials [39–41]. While exact R&D figures for tirzepatide are not public, Lilly's overall GLP-1 investments exceed $20 billion [39–41]. This disparity highlights China's advantage, potentially enabling HRS9531 to launch at a fraction of tirzepatide's U.S. list price (~$1,086/month), boosting accessibility [42,43].

Risks to Monitor

Challenges include intellectual property disputes in the patented dual-agonist space [44], pending long-term (>48 weeks) data [7,45], manufacturing scale-up [39], and intensifying competition from biosimilars, novel multi-agonists, and oral formulations [28,46]. Regulatory or supply delays could hinder rollout [1,47].

Outlook: A Fiercer Market Ahead

With approval timelines of 12–16 months, HRS9531 could launch by Q4 2026 [1,48]. As China's most efficacious clinical-stage injectable obesity drug, it offers a robust alternative to tirzepatide, potentially democratizing access [9,23]. However, emerging oral GLP-1s like orforglipron and higher-dose oral semaglutide could fragment the market by prioritizing convenience over maximal efficacy, though injectables may dominate for severe cases [15,19,50]. Success will depend on extended data, strategic pricing, supply ramp-up, and global expansion via Kailera, in a market forecasted to exceed $100 billion globally by 2030 [24,49].

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