FDA Granted Certolizumab Pegol Breakthrough Status for APS in Pregnancy

Certolizumab pegol IMPACT trial design and primary results in APS pregnancy

The FDA has granted Breakthrough Therapy designation to certolizumab pegol (Cimzia) for preventing placenta-mediated adverse pregnancy outcomes in pregnant women with antiphospholipid syndrome (APS) who are positive for lupus anticoagulant and have prior obstetric or thrombotic events.^¹ UCB announced the designation September 9, 2026, citing preliminary results from the investigator-sponsored IMPACT trial.^¹ No FDA-approved therapies currently exist for this indication, where standard care relies on low-dose aspirin and heparin.^¹

Certolizumab pegol, a tumor necrosis factor (TNF) inhibitor, is already approved for several rheumatic indications, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and nonradiographic axial spondyloarthritis.^¹ According to UCB, evidence implicates TNF-mediated inflammation in APS-related pregnancy complications, providing mechanistic rationale for extending the drug to this population.^¹

The Breakthrough Therapy designation is supported by preliminary results from the IMPACT trial (IMProve Pregnancy in APS with Certolizumab Therapy), a prospective, single-arm, open-label phase 2 study co-led by Jane E. Salmon, MD, Collette Kean Research Chair, Hospital for Special Surgery.^² The trial enrolled 51 pregnant patients with APS and lupus anticoagulant positivity, with 45 evaluable for the primary outcome after excluding early pregnancy losses and genetically related fetal deaths.^² Patients received certolizumab pegol from gestational week eight through week 28, alongside low molecular weight heparin and low-dose aspirin.^²

The primary outcome was a composite of fetal death at or beyond 10 weeks' gestation, pre-eclampsia with severe features, and placental insufficiency requiring delivery before 34 weeks.^² Nine of 45 evaluable patients experienced this composite adverse pregnancy outcome, an incidence of 20% (95% CI, 9.6%-34.6%).^² The result met the trial's predefined efficacy threshold and was lower than rates reported in historical controls, according to the published results.^²

Certolizumab pegol secondary outcomes and safety in APS pregnancy

Among evaluable patients, median gestational age at delivery was 36.5 weeks.^² Neonatal survival to hospital discharge was 93%, and deliveries among patients who met the composite adverse outcome criteria, primarily pre-eclampsia, occurred after 30 weeks' gestation.^² These secondary findings were reported alongside the primary result in the published IMPACT analysis.^²

No serious infections, new cases of lupus, or severe disease flares were reported during the treatment period, according to the published trial results.^²

Jane E. Salmon, MD, Collette Kean Research Chair at the Hospital for Special Surgery and co-lead investigator of the IMPACT trial, said, “For women living with APS, pregnancy can be an especially challenging and uncertain experience. Today's designation represents an encouraging step forward in efforts to improve outcomes for women of childbearing age and their families.”^¹

Donatello Crocetta, Chief Medical Officer and Global Head of Medical Affairs at UCB, added, “This designation is a testament to UCB's commitment to advancing innovation in areas of significant unmet need, including our long-standing focus on supporting women of childbearing age.”^¹

UCB said the designation builds on the company's broader focus on medicines for women of childbearing age, and the company plans continued engagement with the FDA as development in this indication proceeds.^¹

References

1. UCB. UCB receives US FDA breakthrough therapy designation for CIMZIA (certolizumab pegol) in pregnant women with antiphospholipid syndrome (APS). Published September 9, 2026. Accessed September 9, 2026. https://www.prnewswire.com/news-releases/ucb-receives-us-fda-breakthrough-therapy-designation-for-cimziacertolizumab-pegol-in-pregnant-women-with-antiphospholipid-syndrome-aps-302873706.html

2. Branch DW, et al. Certolizumab pegol to prevent adverse pregnancy outcomes in patients with antiphospholipid syndrome and lupus anticoagulant (IMPACT): results of a prospective, single-arm, open-label, phase 2 trial. Ann Rheum Dis. 2025;84(7):1011-1022.

3. US Food and Drug Administration. Breakthrough Therapy. Accessed September 9, 2026. https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy