Obesity Update: ASC47 Combo Gains, Quintuple Agonist, Mazdutide Launch, Pfizer–Metsera Buyout & More!
From dual-action breakthroughs and multi-targeted peptide innovation to China’s first dual GCG/GLP-1 approval, metabolic “reprogramming” strategies, and Pfizer’s splashy Metsera acquisition—this week’s headlines signal rapid progress. Clinical wins, next-gen candidates, and major cross-border pharma deals underscore rising momentum and globalization across obesity and metabolic disease.
In Today’s Newsletter
🧪 ASC47 + semaglutide shows higher early weight loss vs sema alone [1] [22 Sep 2025]
Context: ASC47-103 (NCT06972992), randomized, dbl-blind, PBO-controlled; single-dose ASC47 (10/30/60 mg) + weekly sema 0.5 mg x4 vs sema alone; adults with obesity; n=28; 4-wk treatment.
Key point: Day 29: 30 mg cohort (n=6) showed 56.2% greater relative weight reduction vs sema (n=7); 60 mg cohort 15.1%; pooled ASC47 (n=15) 31.6% greater; sema alone −2.5% from baseline; LDL-C reduced vs sema at 30/60 mg (magnitude not stated).
Implication: May influence prescriber choice and payer reviews pending full data.
🧬 Unimolecular quintuple agonist (GLP-1/GIP + pan-PPAR) outperforms in mice [2] [EU • 21 Sep 2025]
Context: EASD (Vienna) session; design links GLP-1R/GIPR agonism with targeted intracellular delivery of lanifibranor (pan-PPAR) to incretin-receptor–expressing cells; preclinical models.
Key point: In obese/diabetic mice, quintuple agonist reduced body weight, food intake, and hyperglycemia more than GLP-1/GIP or semaglutide; human timing not set.
Implication: Could inform practice and payer discussions; interpretation depends on study design and confounding control.
🔬 RES-010 (miR-22 ASO) aims to “reprogram” fat & energy use; Phase 1 underway [3] [EU • 18 Sep 2025]
Context: Resalis Therapeutics; antisense oligo blocking miR-22; weekly SC; preclinical data plus ongoing Phase 1; EASD presentation.
Key point: In obese mice, weekly dosing led to ~12% greater weight loss vs untreated over 5 months, with durability after stopping; human efficacy not reported.
Implication: Could inform practice and payer discussions; interpretation depends on study design and confounding control.
🇨🇳 Mazdutide wins NMPA approval for glycemic control in adults with T2D [4]
Context: Innovent; dual GCG/GLP-1 receptor agonist; first approval globally for this dual class in T2D glycemic control (per company).
Key point: NMPA approval expected to support glycemic control, weight reduction, and metabolic indicators; label specifics not provided here.
Implication: Introduces competition that may affect pricing and formulary access.
💼 Pfizer to acquire Metsera; adds monthly GLP-1 & amylin programs [5]
Context: Definitive agreement; Boards approved; closing targeted 4Q25 pending approvals. Portfolio includes injectables (weekly/monthly GLP-1; monthly amylin mono/combo) and oral GLP-1s.
Key point: Deal at $47.50/share cash (~$4.9B EV) + CVR up to $22.50/share tied to clinical/regulatory milestones; EASD late-breaker for MET-233i noted.
Implication: Signals pipeline investment and modality expansion.
🏁 Roche advancing CT-388 to late-stage obesity trials [6]
Context: CT-388 acquired via Carmot (2023); early data showed meaningful weight loss; investor-day commentary.
Key point: Roche aims for top-3 obesity market position by 2030; shares rose on late-stage move. Specific phase/endpoints not provided.
Implication: Signals pipeline investment and modality expansion.
🌏 US biopharmas accelerate China in-licensing to refill pipelines [7]
https://www.gabionline.net/reports/more-china-licence-deals-for-us-drug-companies
Context: Summary citing Reuters, GlobalData, NRDD, DealForma.
Key point: 1H25: 14 China-sourced deals, potential $18.3B; 2024: 48 China→West deals worth $8.4B; drivers include patent cliff and cost.
Implication: Signals pipeline investment and modality expansion.
Why it matters
- Combo and poly-agonist strategies are pushing beyond appetite suppression toward multi-pathway metabolic control.
- Durability and monthly dosing are key differentiators as competition intensifies.
- China is shaping both innovation (mazdutide approval) and deal flow (in-licensing surge).
- Big Pharma is consolidating assets to compete with GLP-1 incumbents.
- Early signals (small trials, preclinical) need confirmation before shifting practice.
📢 Stay Ahead in Obesity Updates!
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FAQ
What is ASC47 and how strong are the new data?
ASC47 is a THRβ-targeting, ultra-long-acting SC candidate tested with semaglutide. In a 4-week US study (n=28), the 30 mg cohort had 56.2% greater relative weight reduction vs sema alone at Day 29; pooled analysis showed 31.6% (small n, short duration) [1].
How does the “quintuple agonist” work?
It’s a single molecule with GLP-1R/GIPR agonism plus targeted intracellular delivery of pan-PPAR (lanifibranor) to incretin-receptor cells, aiming to couple appetite/weight effects with insulin sensitization and lipid benefits; data are preclinical in mice [2].
What is RES-010 targeting?
RES-010 is an antisense oligonucleotide against miR-22, a regulator of lipid metabolism and mitochondrial function. Preclinical models showed additional weight loss and durability post-treatment; a Phase 1 is underway (human efficacy not reported) [3].
What did China approve for Innovent?
NMPA approved mazdutide, a dual glucagon/GLP-1 receptor agonist, for glycemic control in adults with T2D—the first approval of this dual class for that use per company statements [4].
What does Pfizer gain from buying Metsera?
Four clinical-stage programs (weekly/monthly GLP-1; monthly amylin mono/combo) plus oral GLP-1s, with a deal priced at ~$4.9B EV and up to $22.50/share in CVRs tied to milestones [5].
Where does Roche stand in obesity?
Roche is moving CT-388 into late-stage trials and aims to be top-3 in obesity by 2030; details on phase/endpoints weren’t provided in the source article [6].
Entities / Keywords
Ascletis; ASC47; semaglutide; THRβ • Helmholtz/DZD; quintuple agonist; GLP-1R; GIPR; lanifibranor; PPAR-α/δ/γ • Resalis; RES-010; miR-22; ASO • Innovent; mazdutide; NMPA; dual GCG/GLP-1 • Pfizer; Metsera; MET-097i; MET-233i; monthly GLP-1; amylin • Roche; CT-388; Carmot • China in-licensing; Reuters; GlobalData; NRDD; DealForma.
References
- https://www.manilatimes.net/2025/09/22/tmt-newswire/pr-newswire/ascletis-announces-asc47-in-combination-with-semaglutide-demonstrated-up-to-562-greater-relative-reduction-in-body-weight-in-participants-with-obesity-compared-to-semaglutide-monotherapy/2187943
- https://www.news-medical.net/news/20250921/New-quintuple-agonist-shows-promise-for-treating-obesity-and-type-2-diabetes.aspx
- https://www.news-medical.net/news/20250918/Scientists-unveil-new-obesity-drug-that-reprograms-fat-and-energy-use.aspx
- https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-received-approval-from-chinas-nmpa-for-glycemic-control-in-adults-with-type-2-diabetes-302561434.html
- https://www.stocktitan.net/news/PFE/pfizer-to-acquire-metsera-and-its-next-generation-obesity-apxqz09hvzwb.html
- https://www.devdiscourse.com/article/headlines/3636235-roches-bold-move-aiming-to-topple-giants-in-the-obesity-drug-market
- https://www.gabionline.net/reports/more-china-licence-deals-for-us-drug-companies