Year-End Patent News and Phase 3 Moves
Week Of December 27 – January 2, 2026
It was a relatively quiet news week as the year closed out. The main headline was Novo Nordisk’s semaglutide patent win in China’s Supreme Court - more of a legal housekeeping item than a clinical development. The trial registry was busier, with Metsera’s MET097 advancing to Phase 3 with a 3,500-patient study. Given that Pfizer recently acquired Metsera, this represents a significant late-stage bet on what they’re calling a “next-generation” GLP-1 mono-agonist with potentially better tolerability. MET097 is also what is called a “biased agonist”, which for GLP-1s means favoring cAMP production versus β-arrestin recruitment (see the nice visual for the Mechanism Explained from November 21 for ecnoglutide).
For the Mechanism Explained section this week, I wanted to explore Amgen’s approach with maridebart cafraglutide (AMG 133), which takes the opposite tack from tirzepatide on GIP - blocking the receptor rather than activating it. The genetic data supporting GIP antagonism is interesting, and it’ll be worth watching whether this “push-pull” design provides meaningfully different outcomes than the dual agonist approach.
🔥 THIS WEEK’S KEY DEVELOPMENTS
China’s Supreme Court upholds Novo Nordisk’s semaglutide patent.
On December 31, 2025, Novo Nordisk announced that China’s Supreme People’s Court upheld the validity of its semaglutide compound patent, confirming a previous ruling by the Beijing IP Court. The company stated this decision does not alter its previous communication that the patent expiry in certain countries is expected to have a negative low-single-digit impact on global sales growth in 2026.
Press | Mechanism: glucagon-like peptide-1 (GLP-1) receptor agonist
🆕 NEWLY REGISTERED TRIALS (7 in last week)
Maridebart cafraglutide (AMG 133) Phase I bioavailability study comparing two different subcutaneous presentations of the obesity drug candidate (Amgen, n=340)
[Weight Loss/Efficacy]
Trials: NCT07313761 | Mechanism: GLP-1 Agonism + GIP Receptor Antagonism
MET097 Phase 3 investigating the efficacy and safety of the once-weekly therapy in people with overweight or obesity (Metsera, n=3500)
[Weight Loss/Efficacy | Safety/Tolerability]
Trials: NCT07311850 (VESPER-4) | Mechanism: GLP-1 receptor agonist
GLP-1 RAs Phase 4 trial investigating effects on inflammatory and endothelial biomarkers in patients with type 2 diabetes (Federico II University, n=80)
[New Indications]
Trials: NCT07314684 (STABLE-GLP1) | Mechanism: GLP-1 receptor agonist
Dulaglutide Phase 1 studying the impact of fasting and drug withholding on gastric retention in patients with Type 2 Diabetes (Eli Lilly, n=20)
[New Indications]
Trials: NCT07313813 (GBGT) | Mechanism: GLP-1 receptor agonist
AMG 133 Phase 1 completed drug-drug interaction study with anti-nausea medication in adults with obesity or overweight (Amgen, n=59).
[Weight Loss/Efficacy]
Trials: NCT07310563 | Mechanism: GLP-1 with novel mechanism
ZT006 Phase 1 dose-escalation and food effect study in healthy, overweight, and obese participants (Beijing QL Biopharmaceutical, n=94)
[Weight Loss/Efficacy, Oral Formulations]
Trials: NCT07307638 | Mechanism: GLP-1 receptor agonist (oral)
iGlarLixi Phase 4 real-world study versus standard of care in Chinese adults with uncontrolled type 2 diabetes on oral agents (Shanghai Zhongshan Hospital, n=1316)
[Oral Formulations | Safety/Tolerability]
Trials: NCT07307235 | Mechanism: GLP-1 agonist + basal insulin combination
💡 TRIAL SPOTLIGHT
Educational spotlight selected by editors
Efficacy and Safety of MET097 Once-Weekly in People With Overweight or Obesity (VESPER-4)
This Phase 3 pivotal trial evaluates MET097, a novel ultra-long-acting GLP-1 receptor agonist, in 3,500 participants managing overweight or obesity. Distinguished by its proprietary HALO™ lipidation technology, MET097 is engineered for an extended half-life (approximately 15 days) and “fully biased” receptor engagement, a mechanism designed to maintain potent weight-loss efficacy while potentially reducing gastrointestinal side effects like nausea. While the molecule’s durability theoretically supports once-monthly dosing, this specific study assesses a once-weekly regimen, likely to optimize therapeutic exposure and establish a competitive efficacy profile against established daily or weekly agents. The trial is strategically significant as the flagship late-stage effort for Metsera (recently acquired by Pfizer), marking a major bid to introduce a “next-generation” mono-agonist with best-in-class tolerability into the global obesity market.
🔬 MECHANISM EXPLAINED
Understanding the science behind the therapeutics
GLP-1 Agonism with GIP Receptor Antagonism (Example: Maridebart Cafraglutide (AMG 133))
Maridebart cafraglutide represents a novel antibody-peptide conjugate design, linking a monoclonal antibody that inhibits the glucose-dependent insulinotropic polypeptide (GIP) receptor to two peptides that activate the GLP-1 receptor. While GLP-1 activation drives established benefits like satiety and insulin secretion, the decision to block rather than activate GIP distinguishes this mechanism from co-agonists like tirzepatide. This approach is grounded in human genetic data showing that loss-of-function variants in the GIP receptor are associated with lower body mass index and protection against obesity. Physiologically, GIP is known to promote lipid storage in adipose tissue; therefore, antagonizing this receptor may limit fat accumulation while GLP-1 promotes weight loss. This “push-pull” synergy—driving satiety while preventing fat storage—aims to deepen weight loss efficacy and potentially improve durability compared to GLP-1 mono-agonism.
This newsletter compiles publicly available information from company press releases and ClinicalTrials.gov. Not investment advice.