European Commission approves Tremfya (guselkumab), the first dual-acting IL-23 inhibitor offering both subcutaneous and intravenous induction options, for adult patients with moderately to severely active Crohn’s disease - Johnson & Johnson

Johnson & Johnson announced that the European Commission (EC) has approved a Marketing Authorisation (MA) for Tremfya (guselkumab), the first dual-acting IL-23 inhibitor offering both intravenous (IV) and subcutaneous (SC) induction options, for the treatment of adults with moderately to severely active Crohn’s disease (CD) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic treatment. This milestone builds upon the recent EC approval of guselkumab in moderately to severely active ulcerative colitis (UC).  CD and UC are the two main forms of inflammatory bowel disease (IBD), which affects over four million people in Europe.

“Despite the progress made in the management of Crohn’s disease, many patients experience debilitating symptoms and are in need of new treatment options, said Professor Silvio Danese, Director, Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy. “The approval of guselkumab offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens and higher rates of endoscopic remission when compared to ustekinumab. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and healthcare professionals that has not been available before."

This approval is supported by results from the Phase III  GALAXI and GRAVITI programmes in moderately to severely active CD, in adults who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic treatment. Data from the pooled Phase III GALAXI 2 and 3 studies, which evaluated guselkumab IV induction and SC maintenance therapy, showed that guselkumab demonstrated greater efficacy compared to ustekinumab in endoscopic response  and endoscopic remission  at Week 48, the only IL-23 inhibitor to achieve this in a double-blinded registrational programme. The GRAVITI study evaluated guselkumab SC induction and maintenance therapy versus placebo following 12 weeks of induction and at 48 weeks of maintenance therapy. The results from these Phase III studies demonstrated the efficacy of IV or SC guselkumab in achieving clinical and endoscopic endpoints.

Highlights from these registrational studies showed:

1. GALAXI: i) In the pooled GALAXI 2 and 3 studies, at Week 48, guselkumab demonstrated greater efficacy in endoscopic response with 200 mg IV induction followed by 100 mg SC q8w (48%) or 200 mg SC q4w (53%) compared to ustekinumab (37%). ii) Also in the pooled GALAXI 2 and 3 studies, endoscopic remission at Week 48 was achieved with greater efficacy with guselkumab 200 mg IV induction followed by 100 mg SC q8w (25%) or 200 mg SC q4w (21%) compared to ustekinumab (16%).

2. GRAVITI: i) At Week 12, patients treated with guselkumab 400 mg SC induction achieved clinical remission (56%) and endoscopic response (41%%) vs placebo (both 21%). ii) Clinical remission at Week 48 was achieved in patients treated with guselkumab 400 mg SC induction followed by 100mg SC q8w (60%) or 200mg SC q4wi (66.1%) as maintenance vs placebo (17.1%). iii) Endoscopic reponse at Week 48 was achieved in patients treated with guselkumab 400 mg SC induction followed by 100 mg SC q8w (44.3%) or 200mg SC q4w (51.3%) as maintenance vs placebo (6.8%).

Safety results from both GALAXI studies and the GRAVITI study were consistent with the known safety profile of guselkumab in approved indications in psoriasis, psoriatic arthritis, and UC.

“Guselkumab is the first approved fully-human, dual-acting IL-23 inhibitor that offers a fully subcutaneous option for moderately to severely active Crohn’s disease. With the approval of guselkumab, it is now possible to achieve meaningful improvements in clinical and endoscopic outcomes,” said Mark Graham, Senior Director, Therapeutic Area Lead, Immunology, J&J Innovative Medicine EMEA. “Guselkumab provides people living with Crohn’s disease and healthcare professionals a new treatment option that is supported by data from multiple Phase 3 studies, showing greater efficacy versus ustekinumab across endoscopic response and endoscopic remission.

For the treatment of CD, the recommended induction dose is 200 mg administered by IV infusion at Week 0, Week 4, and Week 8, or 400 mg administered by SC injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4 and Week 8. After completion of the induction dose regimen, the recommended maintenance dose starting at Week 16 is 100 mg administered by subcutaneous injection every 8 weeks (q8w). Alternatively, for patients who do not show adequate therapeutic benefit to induction treatment according to clinical judgement, a maintenance dose regimen of 200 mg administered by subcutaneous injection starting at Week 12 and every 4 weeks (q4w) thereafter, may be considered.

This EC approval marks the fourth approved indication for guselkumab in the European Union (EU).

ABOUT THE GALAXI PROGRAMME (EudraCT 2017-002195-13)
GALAXI is a double-blind, placebo-controlled, active-controlled (ustekinumab), parallel group, global, multicentre Phase II/III programme designed to evaluate the efficacy and safety of guselkumab in participants with moderately to severely active Crohn’s disease with inadequate response/intolerance to conventional therapies (immunomodulators, corticosteroids) and/or biologics (infliximab, adalimumab, certolizumab pegol, vedolizumab). GALAXI includes a Phase II dose-ranging study (GALAXI 1) and two independent, identically designed confirmatory Phase III studies (GALAXI 2 and 3, n=1021). Each GALAXI study employed a treat-through design in which participants remained on the treatment to which they were initially randomised and includes a long-term extension that will assess clinical, endoscopic, and safety outcomes with guselkumab through a total of five years.

ABOUT THE GRAVITI Phase III study (EudraCT 2020-006165-11)
GRAVITI is a double-blind, placebo-controlled, parallel group, global, multicentre study to evaluate the efficacy and safety of guselkumab subcutaneous induction therapy in 347 participants with moderately to severely active Crohn’s disease with inadequate response or failure to tolerate previous conventional therapy (corticosteroids or immunomodulators) or biologic therapy (infliximab, adalimumab, certolizumab pegol, vedolizumab). The study has a treat-through design in which participants remained on the treatment to which they were initially randomised and includes a long-term extension that will assess clinical, endoscopic, and safety outcomes with guselkumab through a total of five years.