The BioPharm Brief: Ivonescimab Priority Review in China, Stargardt Gene Therapy Moves Toward Phase 3, and Longer Dosing Intervals for an IBD Bispecific

Welcome to The BioPharm Brief, your daily snapshot of developments shaping the biopharmaceutical industry. Today we cover a regulatory step for a bispecific in biliary tract cancer, a path to phase 3 for an eye disease gene therapy, and early data that could allow less frequent dosing in inflammatory bowel disease.

First, China’s National Medical Products Administration has granted priority review to Akeso’s ivonescimab plus chemotherapy for first-line treatment of locally advanced or metastatic biliary tract cancer. Ivonescimab is a bispecific antibody that blocks both PD-1 and VEGF. The application is supported by the phase 3 HARMONi-GI1 trial in 682 patients, which compared ivonescimab with durvalumab, each given with gemcitabine and cisplatin. At a prespecified interim analysis, median overall survival was 14.9 months with ivonescimab versus 12.1 months with the durvalumab regimen. Median progression-free survival was 8.4 versus 5.8 months. According to Akeso, it is the first phase 3 trial in this cancer to show a significant overall survival benefit over a PD-L1 inhibitor plus chemotherapy. Priority review does not guarantee approval, and no timeline for a decision has been disclosed.

Next, VeonGen Therapeutics has reached alignment with FDA on the pivotal phase 3 design and manufacturing strategy for VG801, its gene therapy for Stargardt disease and other ABCA4-related retinal dystrophies. The ABCA4 gene is too large to fit in a single AAV vector. VG801 splits the gene across two vectors, and the pieces are rejoined at the mRNA level once inside the cell. VeonGen says it agreed with FDA on the primary endpoint, study duration, and control arm, and on using its existing clinical batch for the pivotal study. VeonGen did not disclose what those design choices are. In the open-label phase 1/2 trial, all 13 patients with a measurable baseline gained visual acuity, and 11 gained at least five letters on a standard eye chart. The study is small and uncontrolled, and Stargardt disease currently has no approved treatment.

And finally, Caldera Therapeutics reported phase 1a data for CLD-423, a bispecific antibody that blocks IL-23p19 and TL1A. In 56 healthy volunteers, the estimated intravenous half-life was more than 40 days, which Caldera says supports subcutaneous maintenance dosing every 8 or 12 weeks. Free TL1A fell below detectable levels within two hours at every dose, and the drug was generally well tolerated. Caldera plans to file an investigational new drug application for a phase 2b trial in ulcerative colitis this quarter, and a phase 2a Crohn’s disease study in China is expected to begin dosing in early 2027.

That’s today’s BioPharm Brief. For analysis and expert insights, please visit BioPharmInternational.com.

Key takeaways

• Head-to-head evidence: Ivonescimab beat a durvalumab regimen on overall survival in a phase 3 trial, which supports its filing in a cancer with limited first-line options.
• De-risking gene therapy: Agreeing with FDA on trial design and manufacturing before phase 3 starts lowers regulatory uncertainty for VG801, but the clinical evidence so far comes from a small, uncontrolled study.
• Dosing convenience: Caldera is betting that hitting two targets with one molecule, dosed only every 8 to 12 weeks, can stand out among IBD therapies.