AstraZeneca, Pharmacokinetics, and a Crowded Pipeline
Week Of April 4 – April 10, 2026
This week’s Trial Spotlight is about AstraZeneca. They now have over 20 obesity trials spanning oral GLP-1s, amylin agonists, dual agonists, and a designed combination of two of them. Their ASCEND Phase 2 combo trial reads out in May. I go into what they’re building in the Mechanism Explained, which covers the engineering challenge of extending GLP-1 dosing from weekly to monthly and quarterly, from Fc fusion to circular RNA. Separately, 23andMe published data this week suggesting genetics may modestly predict who responds well to GLP-1 drugs. Pharmacogenomics in this space is still very early, but it’s a thread I expect to hear more about.
🔥 THIS WEEK’S KEY DEVELOPMENTS
Foundayo (orforglipron) now available in the US.
Eli Lilly’s once-daily oral GLP-1, Foundayo (orforglipron), is now available in the U.S. for adults with obesity or overweight with weight-related medical problems, following FDA approval on April 1. In the ATTAIN-1 trial, patients on the highest dose lost an average of 27.3 pounds (12.4%) at 72 weeks vs 2.2 pounds (0.9%) for placebo. Available through LillyDirect, telemedicine providers, and retail pharmacies.
Press | Trials: NCT05869903 | Mechanism: oral non-peptide GLP-1 receptor agonist
FDA warns of counterfeit Ozempic in US supply chain and clarifies compounding policies.
The FDA issued a warning about counterfeit Ozempic (semaglutide) found in the US drug supply, urging consumers to verify their sources. Separately, the agency clarified compounding policies as national GLP-1 supply stabilizes, and issued warning letters to multiple compounding pharmacies (PekCura Labs, Mile High Compounds, Gram Peptides, Pink Pony Peptides) over unapproved semaglutide and tirzepatide products.
Wegovy HD now available nationwide; EU approves 48-hour room-temperature storage.
Novo Nordisk launched higher-dose Wegovy HD nationwide in the US. Separately, Wegovy became the first GLP-1 weight-loss treatment approved for 48-hour controlled-temperature delivery in the EU, easing cold-chain requirements for patients.
📰 PRESS
MetaVia doses first patient in higher-dose Phase 1 of DA-1726, a GLP-1/glucagon dual agonist for obesity.
Press | Mechanism: GLP-1/glucagon dual agonist
23andMe finds genetic changes appear to help predict response to GLP-1 drugs for weight loss.
Gan & Lee licenses GLP-1 agonist bofanglutide to JW Pharmaceutical for South Korean market.
Press | Mechanism: GLP-1 receptor agonist
Vivtex expands beyond its $2.1B Novo Nordisk deal for oral drug delivery technology.
Press | Mechanism: oral drug delivery
Vanda initiates study of motion sickness drug Nereus in GLP-1 users.
Ascletis announces fixed-dose combination of ASC30 (oral GLP-1) and ASC39 (oral amylin agonist) for clinical development.
Press | Mechanism: GLP-1 + amylin combination
💡 TRIAL SPOTLIGHT
Educational spotlight selected by editors
ASCEND: Inside AstraZeneca’s Quiet Bet on a Multi-Mechanism Obesity Combination
AstraZeneca’s ASCEND trial (NCT06862791) is an active Phase 2 study of 377 patients set to read out in May 2026, offering the first major look at an expansive, under-the-radar obesity pipeline hiding in plain sight. The trial evaluates the co-administration of two distinct injectables against placebo and each component alone: AZD9550, a unimolecular GLP-1/glucagon dual agonist, and AZD6234, a novel long-acting selective amylin receptor agonist (SARA) engineered to avoid the calcitonin-mediated aversion associated with broader amylin drugs. Because the components are delivered as separate injections rather than a fixed co-formulation like Novo Nordisk’s CagriSema, ASCEND allows for independent dose optimization of what is effectively a de facto triple-pathway metabolic intervention. This aggressive combination serves as the centerpiece of AstraZeneca’s quietly assembled obesity portfolio, which spans over 20 trials and includes the oral GLP-1 elecoglipron as well as the newly registered, undisclosed-mechanism AZD1043. It signals a major strategic pivot for a company not historically known for obesity drug development. While combining multiple metabolic mechanisms inherently increases tolerability risks and clinical complexity, a successful ASCEND readout could allow AstraZeneca to leapfrog competitors by establishing a highly differentiated, next-generation approach to weight loss.
ClinicalTrials.gov: NCT06862791 (ASCEND) | NCT06579092 (VISTA - Elecoglipron) | NCT06579105 (SOLSTICE - Elecoglipron)
🔬 MECHANISM EXPLAINED
Understanding the science behind the therapeutics
Beyond Weekly: The Engineering Race to Build Monthly and Quarterly GLP-1 Therapies (Example drugs: PF-08653944, Efsubaglutide, CR059)
As the obesity landscape pushes beyond the weekly dosing standard set by semaglutide’s acylation-driven albumin-binding approach, drug designers are turning to increasingly creative molecular engineering to push toward monthly or even quarterly dosing. Rather than relying solely on fatty acid side chains that eventually hit a clearance ceiling, next-generation candidates utilize Fc domain fusion to hijack the IgG endosomal recycling pathway - effectively tricking the body into preserving the drug the way it preserves its own antibodies (efsubaglutide), increase hydrodynamic radius through PEGylation (loxenatide), encapsulate existing drugs in slow-release matrices (NEX-22A), or feature fundamentally redesigned ultra-long-acting peptides (Pfizer/Metsera’s PF-08653944). More radical moonshots, like CirCode Bio’s CR059, bypass protein half-life limitations entirely by utilizing circular RNA lipid nanoparticles to turn the patient’s own cells into long-term drug factories. While extending dosing intervals promises to drastically improve real-world adherence and enable convenient multi-target regimens like monthly amylin combinations, it introduces complex pharmacokinetic trade-offs, including slower dose titration, delayed steady-state efficacy, and prolonged washout periods if severe adverse events occur. With PF-08653944 and efsubaglutide registering new clinical trials this week alongside promising quarterly dosing data from Ascletis (ASC30), the competitive frontier of incretin therapeutics has officially evolved from maximizing raw weight loss to engineering ultimate pharmacokinetic endurance.
ClinicalTrials.gov: NCT07519135 (PF-08653944) | NCT07518121 (Efsubaglutide) | NCT07347080 (CR059)
🆕 NEWLY REGISTERED TRIALS (7 in last week)
PF-08653944 Phase 1 study evaluating the drug in participants with and without impaired liver function (Pfizer, n=26)
[Safety/Tolerability]
Trials: NCT07519135 | Mechanism: GLP-1 receptor agonist
ASCEND-1 evaluating lifestyle intervention plus mazdutide for weight management in a hospital-sponsored study (Shanghai Zhongshan Hospital, n=420)
[Weight Loss/Efficacy]
Trials: NCT07517042 | Mechanism: Dual GLP-1/glucagon agonist
Efsubaglutide Alfa Phase I bridging study evaluating the drug in healthy adults in Brazil (Shanghai Yinnuo Pharmaceutical Technology Co., Ltd., n=48)
[Safety/Tolerability]
Trials: NCT07518121 (BRIDGE-BR) | Mechanism: GLP-1 receptor agonist
ABBV-295 Phase 1 assessing safety and pharmacokinetics in healthy Japanese adults with overweight or obesity (AbbVie, n=24)
[Weight Loss/Efficacy | Safety/Tolerability]
Trials: NCT07514260 | Mechanism: Dual amylin/calcitonin receptor agonist
AZD1043 Phase 1 trial evaluating the safety and tolerability of a new potential treatment for adults with overweight or obesity (AstraZeneca, n=112)
[Weight Loss/Efficacy | Safety/Tolerability]
Trials: NCT07511205 | Mechanism: Mechanism not disclosed
Low-dose semaglutide Phase 4 trial investigating weight loss in obese, non-diabetic Pakistani adults (Asian Institute Of Medical Sciences, n=60)
[Weight Loss/Efficacy | New Indications]
Trials: NCT07513168 | Mechanism: GLP-1 receptor agonist
GLP-1 Receptor Agonists Phase 2 trial investigating improved outcomes in patients undergoing endovascular thrombectomy for stroke (Population Health Research Institute, n=100)
[New Indications]
Trials: NCT07511543 (LEAST) | Mechanism: GLP-1 receptor agonist
This newsletter compiles publicly available information from company press releases and ClinicalTrials.gov. Not investment advice.
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