Phase III GRAVITI Trial Data Power sBLA Submission for Tremfya to Treat Crohn Disease

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Johnson & Johnson has submitted a supplemental Biologics License Application (sBLA) to the FDA for Tremfya (guselkumab) subcutaneous (SC) induction for the treatment of adult patients with moderately to severely active Crohn disease based on positive topline data from the pivotal Phase III GRAVITI trial (NCT05197049).^1,2

Tremfya was the first FDA-approved, fully-human, dual-acting monoclonal antibody to block interleukin (IL)-23—a significant driver of the pathogenesis of inflammatory diseases—by attaching to the p19 subunit of IL-23 and to CD64, a receptor on cells that produce IL-23.

Tremfya has previously gained FDA approval to treat adults with active psoriatic arthritis and for adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

"Building upon nearly three decades of leadership and innovation in immunology, we are committed to addressing the needs of people living with Crohn's disease through deep, scientific expertise and through our continued pioneering advances in the IL-23 pathway," David Lee, MD, PhD, Global Therapeutic Area Head Immunology, Johnson & Johnson Innovative Medicine, said in a press release. "Tremfya has the potential to be a differentiated treatment option for patients who seek symptom relief and sustained remission. We look forward to working with the Agency in their review of the data supporting the application as we continue to innovate for people living with inflammatory bowel disease."¹

The randomized, double-blind, placebo-controlled GRAVITI trial analyzed Tremfya SC induction at a dose of 400 mg at weeks zero, four, and eight in patients with moderately to severely active Crohn disease who did not achieve an adequate response with or who failed to tolerate conventional therapy—such as corticosteroids or immunomodulators—or biologic therapy, including TNF antagonists or vedolizumab. Investigators used a treat-through design for the trial, which randomly assigned patients to Tremfya at the start of the trial to stay on the regimen through its duration, regardless of clinical response status at the end of induction. Patients randomly assigned to placebo were able to receive guselkumab 400 mg SC q4w x3 to 100 mg SC q8w if rescue criteria were met after 16 weeks.

The trial is part of the randomized, double-blind, placebo-controlled, active-controlled (Stelara [ustekinumab]), global, multicenter Phase II/III GALAXI program. The program includes the Phase II dose-ranging GALAXI 1 trial and the independent, identically designed, confirmatory Phase III GALAXI 2 and 3 trials, all of which employed the treat-through design.²

The GRAVITI trial achieved both of its co-primary endpoints, with statistically significant and clinically meaningful outcomes for clinical remission, as well as endoscopic response, after 12 weeks. The other multiplicity-controlled secondary endpoints were found to be statistically significant in comparison with placebo at weeks 12, 24, and 48.

These findings build on data from the double-blind, registrational, head-to-head GALAXI 2 and GALAXI 3 clinical trials, in which Tremfya showed superiority compared with Stelara across endoscopic endpoints in Crohn disease. In terms of safety, GRAVITI trial data were consistent with the previously established profile of Tremfya, with no new safety signals reported.² Full results from the GRAVITI trial will be presented at upcoming medical meetings, according to Johnson & Johnson.

"The Phase III GRAVITI study showed promising results with SC induction and provides similar clinical benefit to what was seen with IV induction in the GALAXI studies," said David Lee, MD, PhD, Global Therapeutic Area Head Immunology, Johnson & Johnson Innovative Medicine. "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."²

References

Johnson & Johnson submits application to U.S. FDA seeking approval of TREMFYA® (guselkumab) for the treatment of moderately to severely active Crohn's disease. News release. Johnson & Johnson. June 20, 2024. Accessed June 21, 2024. https://www.prnewswire.com/news-releases/johnson--johnson-submits-application-to-us-fda-seeking-approval-of-tremfya-guselkumab-for-the-treatment-of-moderately-to-severely-active-crohns-disease-302178478.html

2. TREMFYA® (guselkumab) studies underscore its potential to be the only IL-23 inhibitor to offer both subcutaneous and intravenous induction. News release. Johnson & Johnson. June 20, 2024. Accessed June 21, 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