Pregnancy outcomes following exposure to galcanezumab: Analysis of cases from the galcanezumab clinical trials and postmarketing database.

Abstract

This study was conducted to describe pregnancy outcomes reported following maternal or paternal exposure to galcanezumab in clinical trials and postmarketing surveillance. Galcanezumab is a calcitonin gene-related peptide-inhibiting monoclonal antibody indicated for the preventive treatment of migraine. This long-acting injectable medication has a half-life of 27 days. Despite high migraine prevalence in women during their childbearing years, information on the use of migraine preventive medications during pregnancy is limited. This is a pooled analysis of clinical trial data with a descriptive case series from a pharmacovigilance database. First, all completed phase 1-3 galcanezumab clinical trials were searched for cases of pregnancy. Additionally, the manufacturer's worldwide safety database was searched for all postmarketing reports of galcanezumab-exposed pregnancy through September 27, 2024. Maternal and fetal outcomes, trimester of exposure, and maternal risk factors were evaluated. In all, 52 pregnancies with maternal or paternal exposure were identified in 12 clinical trials, and 426 were identified in postmarketing reports. In clinical trials, pregnancy exposure to the full therapeutic galcanezumab concentration did not exceed the first trimester. Because of its long half-life, subtherapeutic galcanezumab concentrations persisted into the second trimester in 16 of 30 maternal exposures. The exposure pattern was similar in postmarketing reports when information on the timing of dosing and conception was available, with 88 of 108 confirmed maternal exposures at therapeutic concentrations during the first trimester only, and 34 of 47 confirmed maternal exposures at subtherapeutic concentrations during the first and second trimester. Among pregnancies with reported outcomes, live births were recorded in 22 of 34 clinical trial pregnancies and 62 of 108 postmarketing pregnancies. Among pregnancies with available fetal outcome data, normal fetal outcomes were reported in 21 of 22 clinical trial pregnancies and 56 of 76 postmarketing pregnancies. Preexisting maternal risk factors were identified in 11 of 14 preterm births (three from clinical trials and 11 from postmarketing) and 23 of 44 spontaneous abortions (three from clinical trials and 41 from postmarketing). Nine cases of major congenital anomaly were identified among postmarketing cases, with none identified in clinical trials. Among these nine cases, no consistent pattern of system organ class involvement was observed, and five of the nine anomalies had a one or more relevant maternal risk factor. Based on the available data from this pooled analysis, this review did not identify any qualitative safety signal suggesting a causal relationship between galcanezumab exposure and adverse maternal or fetal outcomes. Because exposure durations were often limited and follow-up information was unavailable for many cases, no definitive conclusions can be drawn regarding the safety of galcanezumab during pregnancy. Migraine is most frequent in women during their childbearing years, yet little is known about the safety of the class of migraine preventive medications known as calcitonin gene‐related peptide inhibitors in pregnancy, so we reviewed available data related to pregnancies in which galcanezumab was used. In this pooled analysis, we saw no potential difference in outcome between galcanezumab‐ and placebo‐exposed pregnancies in clinical trials and no evidence of adverse pregnancy outcomes with galcanezumab use in safety information gathered after the drug became available to patients. Until more safety data are available, it remains crucial for patients taking galcanezumab to discuss conception planning with their health care provider.