VIENNA — according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.
“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.
These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.
Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.
Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
GALAXI 2 and 3 Pooled Dataset
In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.
Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.
Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.
The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.
Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.
The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.
The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
