FDA requests Foundayo post-market liver and heart data; Australia's TGA warns on unapproved peptides; PEPITEM matches infliximab for arthritis; AI discovers novel antimicrobials.
10 stories · Covering regulatory, research, clinical-trials, industry
Today's digest captures a peptide landscape in tension between unprecedented therapeutic promise and intensifying regulatory scrutiny. The headline story — the FDA requesting post-market liver injury and cardiovascular data from Eli Lilly just two weeks after Foundayo's fast-track approval — signals that the agency's appetite for rapid GLP-1 approvals comes with strings attached. Australia's TGA became the third major regulator (after Health Canada and the UK's MHRA) to issue formal warnings on unapproved peptides this month, suggesting a coordinated global tightening. Meanwhile, the non-GLP-1 peptide pipeline continues to deliver: Birmingham researchers showed the natural peptide PEPITEM matched infliximab for arthritis without immunosuppression, a Phase 1 peptide vaccine achieved 75% disease control in a rare liver cancer, and AI-generated antimicrobial peptides published in Nature Microbiology outperformed clinical antibiotics against superbugs. The Oral & Macrocyclic Peptides Summit opening in San Diego today underscores the field's momentum toward solving the oral delivery challenge that could unlock the next generation of peptide drugs.
The FDA asked Eli Lilly for additional safety data on liver injury linked to Foundayo (orforglipron), plus post-marketing trials to assess cardiovascular event risk and delayed gastric emptying. A lactation study was also required. The letter, signed April 1, was published April 14 — just two weeks after the drug's fast-track approval under the National Priority Voucher program.
Australia's Therapeutic Goods Administration warned of rising imports of unapproved peptide products promoted on social media, citing risks including severe allergic reactions, systemic inflammatory response, infection, and organ damage. Named products include BPC-157, GHK-Cu, TB-500, retatrutide, and CJC-1295 — often supplied as injectables.
University of Birmingham researchers showed that the naturally occurring immunopeptide PEPITEM reduced inflammatory arthritis joint swelling comparably to infliximab in preclinical models — but without the immunosuppressive side effects. Published in Arthritis & Rheumatology, the findings suggest PEPITEM could reduce early-stage reliance on steroids in rheumatoid and psoriatic arthritis.
A Phase 1 trial published in Nature Medicine showed that FLC-Vac, a therapeutic peptide vaccine targeting the DNAJ-PKAc fusion protein in fibrolamellar hepatocellular carcinoma, combined with nivolumab and ipilimumab achieved 75% disease control (9/12 patients) and 25% partial response rate. All responders showed tumor-specific T cell responses.
A study in Nature Microbiology used a generative protein language model (ProteoGPT) to discover novel antimicrobial peptides effective against multidrug-resistant bacteria. The AI-designed peptides showed comparable or superior efficacy to clinical antibiotics in mouse infection models, with reduced resistance development and no organ damage.
Mechanistic data from the REMODEL trial presented at the 2026 World Congress of Nephrology showed semaglutide decreased renal fat, lowered arterial resistance, and stabilized cortical fibrosis. Biopsies revealed reduced immune cells around glomeruli, and transcriptomic analysis identified glomerular endothelial cells as the most responsive cell type to treatment.
A new phage display platform using ~482 venom-derived peptide scaffolds and machine learning-guided mutation design achieved a 100% success rate identifying strong binders across four diverse therapeutic targets (CD47, DLL3, IL33, P2X7R). The approach could accelerate venom peptide drug discovery for cancer, inflammation, and pain.
The Drug Discovery Chemistry Oral & Macrocyclic Peptides Summit (April 14-15, San Diego) convenes as 66 cyclic peptide drugs have gained global approval and the field races to solve oral bioavailability. Key advances include Chugai's Luna18 achieving 21-47% oral bioavailability and Merck's macrocyclic PCSK9 inhibitor enlicitide delivering injectable-level results in pill form.
The FDA published updated guidance clarifying compounding requirements now that semaglutide and tirzepatide shortages have been resolved. The statement reaffirmed enforcement deadlines for 503A and 503B pharmacies while acknowledging ongoing legal challenges from the Outsourcing Facilities Association.
A comprehensive review in Frontiers in Drug Delivery examines the barriers to oral peptide bioavailability — enzymatic degradation, poor membrane permeability, and first-pass metabolism — and maps emerging solutions including permeation enhancers, nanoparticle encapsulation, mucoadhesive systems, and microRNA-based approaches that are advancing toward clinical translation.