Genes, Inflammation, and a Truce
Week Of March 7 – March 13, 2026
RNA interference is making its way into the obesity clinic. This week Alnylam started a Phase 1 trial for ALN-2232, which silences a gene in fat cells rather than targeting appetite circuits in the brain. Alnylam joins Arrowhead, which already has early clinical data for its own ALK7-targeting siRNA, in a race to establish RNA interference (RNAi) as a new therapeutic modality for obesity. I go into how the approach works and why it could complement existing GLP-1s in this week’s Mechanism Explained. On the delivery front, a semaglutide nasal spray entered Phase 1 and Ascletis posted Phase 2 data suggesting quarterly GLP-1 dosing may be feasible - the field continues to push beyond weekly injections. The Trial Spotlight looks at Lilly’s COMMIT program, which is testing whether treating inflammatory bowel disease (IBD) and obesity simultaneously with two of its drugs produces better outcomes than treating either alone. And on the business side, Novo Nordisk and Hims & Hers reached a deal to sell branded Ozempic and Wegovy on Hims’ telehealth platform, ending their patent dispute and the compounding battle.
🔥 THIS WEEK’S KEY DEVELOPMENTS
Novo Nordisk to supply Ozempic, Wegovy through Hims & Hers.
Novo Nordisk announced an agreement with telehealth company Hims & Hers to expand US patient access to its FDA-approved semaglutide medicines. Under the agreement, which takes effect in March 2026, Hims & Hers will offer Ozempic® and Wegovy® injectables, as well as Wegovy® tablets, at Novo Nordisk’s self-pay prices. As part of this shift, Hims & Hers will no longer advertise compounded GLP-1 offerings, and Novo Nordisk is dismissing its patent infringement lawsuit against the company.
Press | Mechanism: GLP-1 receptor agonist
Pfizer, Lilly advance GLP-1 obesity drugs in China.
Chinese authorities have approved Sciwind Biosciences’ injectable GLP-1, ecnoglutide, for the treatment of obesity. In a 48-week trial, patients on the highest dose of ecnoglutide achieved an average weight loss of 15.4% from baseline. Pfizer will market the drug, which is also indicated for Type 2 diabetes, in China. Separately, Lilly committed $3B to expand manufacturing capacity in China through local CDMO partnerships, focused on scaling production of its oral GLP-1 candidate orforglipron.
📰 PRESS
Regeneron’s olatorepatide shows positive Phase 3 results in obesity.
Press | Mechanism: Dual GLP-1/GIP receptor agonist
AbbVie reports positive Phase 1 data for amylin obesity candidate.
Press | Mechanism: Amylin analog
FDA issues warning letter to Novo Nordisk over Ozempic safety reporting.
Press | Mechanism: GLP-1 receptor agonist
Lilly warns of impurities in compounded tirzepatide.
Press | Mechanism: Dual GLP-1/GIP receptor agonist
Lilly invests $126M to expand Japan manufacturing for obesity drugs.
Press | Mechanism: Dual GLP-1/GIP receptor agonist
Novo Holdings reports 34% drop in assets for 2025.
Press | Mechanism: GLP-1 receptor agonist
Ascletis eyes quarterly GLP-1 dosing after Phase 2 obesity data.
Press | Mechanism: GLP-1 receptor agonist
💡 TRIAL SPOTLIGHT
Educational spotlight selected by editors
Lilly’s COMMIT Program: First Trials to Test Whether Treating IBD and Obesity Together Works Better Than Either Alone
Eli Lilly’s COMMIT program represents a significant strategic and conceptual shift in treating inflammatory bowel disease (IBD) by addressing the interconnected pathways of inflammation and metabolic disease. The program consists of two matched Phase 3b trials, COMMIT-UC and COMMIT-CD, which are the first to formally test the co-administration of an IL-23 inhibitor, mirikizumab (Omvoh), with a dual GLP-1/GIP receptor agonist, tirzepatide (Mounjaro/Zepbound). The biological rationale is compelling: obesity, a pro-inflammatory state, can exacerbate IBD and even blunt the efficacy of standard biologic therapies. Simultaneously targeting gut inflammation with mirikizumab and the underlying metabolic dysfunction with tirzepatide may lead to improved outcomes on both fronts. Enrolling a combined 640 patients with either ulcerative colitis or Crohn’s disease who are also overweight or obese across 24 countries, the global trials began recruiting in June 2025, with a rapid recent expansion of 93 new sites this week pushing toward an expected primary completion in spring 2028. As the sole owner of both drugs, Eli Lilly is uniquely positioned to investigate this synergy — signaling a potential new paradigm where IBD is managed holistically, treating the patient’s systemic inflammatory and metabolic profile rather than just their gut-specific symptoms.
🔬 MECHANISM EXPLAINED
Understanding the science behind the therapeutics
RNA Interference Enters the Obesity Race: How Silencing a Single Gene in Fat Cells Could Complement GLP-1 Drugs (Example drugs: ALN-2232, ARO-ALK7)
While existing obesity blockbusters like semaglutide and MariTide modulate appetite circuits in the brain, a new therapeutic modality is taking aim directly at the source: the fat cell itself. Alnylam Pharmaceuticals’ ALN-2232 is an RNA interference (RNAi) therapeutic that silences ACVR1C, the gene encoding the ALK7 receptor, which is highly expressed in adipose tissue. This receptor acts as a metabolic brake, suppressing the breakdown of fat (lipolysis) and promoting catecholamine resistance, a hallmark of obesity. By silencing this gene, ALN-2232 effectively removes these brakes, forcing fat cells to increase fatty acid oxidation and mobilize stored energy — a mechanism supported by human genetic data linking loss-of-function ACVR1C variants to healthier fat distribution and reduced diabetes risk. This direct-to-adipocyte, gene-silencing approach represents a fundamental departure from receptor-based drugs, offering a potentially complementary mechanism that could be paired with brain-acting agents like GLP-1s and dosed as infrequently as quarterly. Alnylam is entering a space where competitor Arrowhead Pharmaceuticals has already shown early clinical promise with a similar ALK7-targeting siRNA, ARO-ALK7. Because this tissue-specific approach works entirely independently of central satiety signaling, it is positioned as a logical, non-overlapping combination partner for existing GLP-1 therapies.
🆕 NEWLY REGISTERED TRIALS (5 in last week)
LY3437943 Phase 2 trial investigating the drug in participants with obesity or who are overweight (Hudson Biotech, n=300)
[Weight Loss/Efficacy]
Trials: NCT07467447 (GZBF) | Mechanism: Triple GLP-1/GIP/glucagon agonist
ALN-2232 Phase 1 evaluating an investigational RNAi therapeutic targeting ACVR1C/ALK7 in adipose tissue for obesity (Alnylam Pharmaceuticals, n=156)
[Weight Loss/Efficacy | Safety/Tolerability]
Trials: NCT07463846 | Mechanism: RNAi (ACVR1C/ALK7 gene silencing)
Tirzepatide Phase 2 trial for the treatment of cannabis use disorder (National Institute on Drug Abuse (NIDA), n=100)
[New Indications]
Trials: NCT07468552 | Mechanism: Dual GLP-1/GIP receptor agonist
Semaglutide Nasal Spray Phase 1 study of a novel formulation for adults who are overweight or obese (Shanghai World Leader Pharmaceutical, n=60)
[Weight Loss/Efficacy | Novel Delivery]
Trials: NCT07465965 | Mechanism: GLP-1 receptor agonist
KAI-9531 Phase 2 trial evaluating a once-weekly treatment for adults with obesity who do not have diabetes (Kailera, n=250)
[Weight Loss/Efficacy | Safety/Tolerability]
Trials: NCT07458269 | Mechanism: Dual GLP-1/GIP receptor agonist
This newsletter compiles publicly available information from company press releases and ClinicalTrials.gov. Not investment advice.
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