GRAVITI: Positive Topline Results for Guselkumab SC Induction in Crohn’s Disease

David Lee, MD, PhD

Credit: Janssen

Johnson & Johnson has announced positive topline results from the phase 3 GRAVITI investigational study of guselkumab (Tremfya) subcutaneous (SC) induction therapy in adult patients with moderately to severely active Crohn's disease (CD).¹

According to the June 20, 2024 press release, the study met all primary and secondary endpoints, including statistically significant and clinically meaningful outcomes for clinical remission and endoscopic response at week 12 and multiplicity-controlled secondary endpoints at weeks 12, 24, and 48. Results are being prepared for presentation at upcoming medical meetings and will be shared with health authorities in planned submissions.¹

"The Phase 3 GRAVITI study showed promising results with SC induction and provides similar clinical benefit to what was seen with IV induction in the GALAXI studies," David Lee, MD, PhD, Global Therapeutic Area Head Immunology, Johnson & Johnson Innovative Medicine, said in a press release.¹ "Having both SC and IV induction options provides choice and versatility for patients and providers. TREMFYA is poised to be the only IL-23 inhibitor to offer a full SC therapy for both induction and maintenance in Crohn's disease."

A fully human monoclonal antibody, guselkumab selectively binds to the p19 subunit of interleukin (IL)-23 and inhibits its interaction with the IL-23 receptor to block the pathogenesis of inflammatory diseases. In addition to studies exploring its use in CD, a separate study evaluating its efficacy and safety in ulcerative colitis is ongoing. Guselkumab is approved by the US Food and Drug Administration for the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis, with its original approval for plaque psoriasis dating back to 2017.²

A randomized, double-blind, placebo-controlled phase 3 study, GRAVITI sought to evaluate guselkumab SC induction therapy (400 mg at weeks 0, 4, and 8) in patients with moderately to severely active CD who experienced an inadequate response or failed to tolerate conventional therapy or biologic therapy. The maintenance doses in GRAVITI are the same as those evaluated in GALAXI (200 mg SC q4w and 100 mg SC q8w). Patients were randomly assigned to guselkumab at week 0 and remained on the same regimen throughout the study, regardless of clinical response status at the end of induction, and participants randomized to placebo were able to receive guselkumab if rescue criteria were met at week 16.¹

GALAXI is a randomized, double-blind, placebo-controlled, active-controlled, global, multicenter phase 2/3 program designed to evaluate the efficacy and safety of guselkumab in participants with moderately to severely active CD with inadequate response/intolerance to conventional therapies and/or biologics. It includes a phase 2 dose-ranging study (GALAXI 1) and a pair of independent, identically designed confirmatory phase 3 studies (GALAXI 2 and 3). Each GALAXI study employed a treat-through design in which participants remained on the treatment to which they were initially randomized and includes a long-term extension study that will assess clinical, endoscopic, and safety outcomes with guselkumab through a total of 5 years.¹

Data from both GALAXI 2 (n = 508) and GALAXI 3 (n = 513) demonstrated the superiority of both subcutaneous maintenance doses of guselkumab 200 mg every 4 weeks and 100 mg every 8 weeks against placebo with greater clinical response and remission. Of note, in GALAXI 2 and 3, both dose cohorts had statistically significant and clinically meaningful differences on all prespecified pooled endoscopic endpoints compared with ustekinumab.^2,3

According to the release from Johnson & Johnson, findings from GRAVITI building upon results from GALAXI 2 and GALAXI 3 suggest guselkumab’s potential to become the only IL-23 inhibitor to offer both SC and IV induction options.¹

References:

1. ^{TREMFYA® (guselkumab) studies underscore its potential to be the only IL-23 inhibitor to offer both subcutaneous and intravenous induction. June 20, 2024. Accessed June 20, 2024. https://www.prnewswire.com/news-releases/tremfya-guselkumab-studies-underscore-its-potential-to-be-the-only-il-23-inhibitor-to-offer-both-subcutaneous-and-intravenous-induction-302177102.html}
2. ^{Brooks, A. Remo Panaccione, MD: GALAXI 2, GALAXI 3 Data for Guselkumab in Crohn’s Disease. HCPLive. May 22, 2024. Accessed June 20, 2024. https://www.hcplive.com/view/remo-panaccione-md-galaxi-2-galaxi-3-data-for-guselkumab-in-crohn-s-disease}
3. ^{Iapoce, C. GALAXI 2 & 3: Guselkumab Superior to Ustekinumab for Crohn's Disease. HCPLive. May 21, 2024. Accessed June 20, 2024. https://www.hcplive.com/view/galaxi-guselkumab-superior-ustekinumab-crohns-disease}