🔥 THIS WEEK’S KEY DEVELOPMENTS
Novo Nordisk to acquire Akero for MASH drug efruxifermin.
[Partnerships/M&A]
Novo Nordisk announced a definitive agreement to acquire Akero Therapeutics for $4.7 billion in cash, with a potential $0.5 billion contingent value right. The acquisition adds efruxifermin (EFX), a Phase 3 FGF21 analogue being developed for metabolic dysfunction-associated steatohepatitis (MASH). In a 96-week Phase 2b trial in patients with compensated cirrhosis (F4), EFX demonstrated a 29% reduction in fibrosis without worsening of MASH, compared to 11% for placebo.
Novo Nordisk highlighted the strategic fit, noting that MASH is closely linked to obesity and diabetes, and stated that EFX, if approved, could become a cornerstone therapy, potentially used alone or in combination with Wegovy (semaglutide), a GLP-1 receptor agonist.
Press | Mechanism: fibroblast growth factor 21 (FGF21) analog
🆕 NEWLY REGISTERED TRIALS (5 in last week)
Macupatide and Eloralintide Phase 2 study testing the drugs alone and in combination for adults with obesity or overweight and type 2 diabetes (Eli Lilly, n=200) [Weight Loss/Efficacy | Oral Formulations] Trials: [NCT07215559] | Mechanism(s): GIP-only agonist (Macupatide) and amylin receptor agonist (Eloralintide)
Individualized Pharmacological Approach... Phase 4 trial testing a personalized medication strategy for obesity in patients with bipolar disorder (Mayo Clinic, n=100) [Weight Loss/Efficacy] Trials: [NCT07213466] | Mechanism: GLP-1 receptor agonist
HM15275 Phase 2 evaluating a treatment for obesity or overweight in subjects without diabetes (Hanmi Pharmaceutical, n=250) [Weight Loss/Efficacy] Trials: [NCT07205900] | Mechanism: Triple GLP-1/GIP/glucagon agonist
Survodutide Phase 2 investigating albuminuria reduction in patients with kidney disease (University Medical Center Groningen, n=120) [New Indications] Trials: [NCT07206290] (ARTIST-CKD) | Mechanism: Dual GLP-1/glucagon agonist
XTL6001 Phase 1 evaluating the safety and tolerability of the injection in healthy and obese subjects (Shanghai Xitaili Biomedicine, n=80) [Weight Loss/Efficacy] Trials: [NCT07205432] | Mechanism: Triple GLP-1/Glucagon/Mas agonist
💡 TRIAL SPOTLIGHT
Educational spotlight selected by editors
A Study of Macupatide (LY3532226) and Eloralintide (LY3841136), Alone or in Combination, in Adults With Obesity or Overweight and With Type 2 Diabetes
Eli Lilly is launching a Phase 2 trial, NCT07215559, to evaluate two novel agents, macupatide and eloralintide, both as individual therapies and in combination. This study will enroll 200 adults with obesity or overweight and type 2 diabetes to assess these different treatment approaches. The trial investigates distinct biological pathways: macupatide is a pure GIP (glucose-dependent insulinotropic polypeptide) receptor agonist, while eloralintide is a selective amylin receptor agonist. Strategically, this trial is significant as it seeks to build upon the success of dual GIP/GLP-1 agonists like tirzepatide by isolating the GIP mechanism and exploring its potential synergy with a non-GLP-1 pathway. By examining a GIP-agonist combined with an amylin mimetic, Lilly is exploring next-generation therapeutic combinations for metabolic diseases that could offer alternative or enhanced benefits.
🔬 MECHANISM EXPLAINED
Understanding the science behind the therapeutics
Dual GLP-1/glucagon agonist (Example: Survodutide (BI 456906))
Dual GLP-1/glucagon receptor agonists represent a next-generation approach in metabolic medicine by simultaneously activating two key hormonal pathways. The GLP-1 (glucagon-like peptide-1) component works by stimulating insulin secretion, slowing stomach emptying, and suppressing appetite in the brain, which are the established effects behind the success of current incretin therapies. Uniquely, this class also activates the glucagon receptor, which, while seemingly counterintuitive as it can raise blood sugar, also increases energy expenditure and promotes fat metabolism. This synergistic combination is designed to produce more significant weight loss and improved metabolic control than targeting the GLP-1 pathway alone. In a competitive landscape dominated by single and dual-incretin drugs from companies like Novo Nordisk and Eli Lilly, these dual-acting molecules aim to offer superior efficacy for obesity and related conditions.
*This newsletter compiles publicly available information from company press releases and ClinicalTrials.gov. Not investment advice.*