UPDATE: Certolizumab Pegol, CIMZIA®, receives FDA Breakthrough Therapy Designation for the Prevention of Adverse Pregnancy Outcomes in Women with Antiphospholipid Syndrome and Lupus Anticoagulant

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to CIMZIA® (certolizumab pegol) for the prevention placenta-mediated adverse pregnancy outcomes (APO) in pregnant women with antiphospholipid syndrome (APS) who test positive for lupus anticoagulant (LA). LA is an autoantibody present in some people with APS and this designation is intended to accelerate the development and review of therapies that show early promise for serious conditions, signaling the FDA’s commitment to speeding up these processes. This announcement marks a significant milestone for the lupus community, as there are currently no targeted treatment options for the prevention of APO in women with APS. The designation follows the FDA’s recent Orphan Drug Designation for CIMZIA® to help prevent placenta-related pregnancy complications in patients with APS. CIMZIA® is not yet approved for this use, and its safety and effectiveness in pregnant patients with APS have not been established.

The IMprove Pregnancy in APS with Certolizumab Therapy (IMPACT) clinical trial, supported by the Lupus Foundation of America through a three-year grant, found that certolizumab pegol, a medication that blocks tumor necrosis factor (TNF), a protein involved in inflammation, in combination with standard therapy, showed potential to prevent APO in women with lupus and or APS. This is the first trial to use a biologic therapy to prevent serious complications in high-risk pregnancies in women with or without lupus and antiphospholipid syndrome (APS). People with lupus can develop APS which can lead to blood clots, and for pregnant women with lupus, pregnancy complications. Poor placental development is one of many complications that can occur, and this leads to inadequate growth of the fetus, preeclampsia and preterm birth. 

The IMPACT study assessed the treatment of certolizumab in 51 pregnant women with APS and LA. In this single-arm, first phase 2 trial, all participants received the biologic therapy from week 8 through 28 of pregnancy, in addition to standard treatment. The study found that 20% of the participants experienced an APO, a number significantly lower than the 40% expected from observational studies of women with APS and LAC women not treated with certolizumab. The study met the pre-established criteria for certolizumab efficacy.  

The 20% complication rate with certolizumab was dramatically lower than IMPACT participants’ prior pregnancies; 69% to 79% had severe adverse outcomes, despite the standard of care treatment with heparin and aspirin. Women who were treated with certolizumab averaged a pregnancy duration of 36.5 weeks, compared to 24 weeks in these participants’ prior pregnancies. In IMPACT, 93% of the women in the study brought home a healthy baby - a remarkable improvement over the 38% survival rate for previous pregnancies among IMPACT participants. Notably, none experienced serious infections or lupus flares, a concern when the study began. 

“We previously showed that pregnancy in lupus patients whose disease is quiescent is likely to be uncomplicated,” says Dr. Jane Salmon, lead investigator of the IMPACT study. “Now with IMPACT, we show the potential to prevent preeclampsia and other serious pregnancy complications in high-risk pregnancies. Our study opens the door for trials with biologics to prevent APOs. We are grateful to the patients and their care providers who were our brave and committed partners in this trial.”  To learn more about the study, check out Dr. Salmon’s study launch video or listen to The Expert Series podcast episode about APS. 

This study shows that focusing on inflammation, rather than thrombosis or blood clots, may help prevent pregnancy complications in high-risk women with lupus and APS. Significant advancements have been made in improving the safety of pregnancy for those living with lupus and more research is needed to explore use of biologics to prevent placenta-mediated APOs.  

The Lupus Foundation of America is proud to have funded the IMPACT study through a three-year grant mechanism specifically developed to address pregnancy outcomes in lupus. Learn more about LFA’s commitment to this study here and learn more about lupus and pregnancy.  

Read the announcement