P4333 - Efficacy and Safety of Subcutaneous Guselkumab Rescue Therapy in Patients With Moderately to Severely Active Crohn’s Disease and Inadequate Response to Ustekinumab: Phase 2 GALAXI 1 Study Long-Term Extension Results

Tuesday, October 29, 2024

10:30 AM – 4:00 PM ET

Location: Exhibit Hall E

Presenting Author(s)

Anita Afzali, MD, MPH, MHCM, FACG

Executive Vice Chair of Internal Medicine, Interim Division Director of Digestive Diseases, Associate Chief Medical Officer
University of Cincinnati College of Medicine
Cincinnati, OH

Anita Afzali, MD, MPH, MHCM, FACG¹, Douglas Wolf, MD², Rupert Leong, MBBS, MD³, Leonardo Salese, MD⁴, Long-Long Gao, PhD⁵, Christopher Busse, MS⁶, Julián Panés, MD⁷
¹University of Cincinnati College of Medicine, Cincinnati, OH; ²Atlanta Gastroenterology Associates, Atlanta, GA; ³Macquarie University Hospital, Sydney, New South Wales, Australia; ⁴Janssen Research & Development, LLC, Horsham, PA; ⁵Janssen Research & Development, LLC, Spring House, PA; ⁶Janssen Scientific Affairs, LLC, Horsham, PA; ⁷Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain

Introduction: Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that is being evaluated in CD. The GALAXI 1 study (NCT03466411) is a phase 2b study that evaluated GUS in participants (pts) with moderate-to-severe CD. Pts treated with ustekinumab (UST) who met inadequate response criteria during long term extension (LTE) could cross over to GUS 200 mg q4w SC. Here, we present efficacy/safety results in pts who received GUS after experiencing an inadequate response to UST in LTE.

Methods: Individuals with prior inadequate response or intolerance to UST were excluded from GALAXI 1; however, during the LTE, pts treated with UST ~6 mg/kg IV→UST 90 mg SC q8w who met inadequate treatment response criteria (not in clinical response [≥100-point reduction in CDAI score from baseline or CDAI< 150] and CDAI ≥220) between Wks 52-80 of LTE were eligible for a treatment switch to GUS 200 mg q4w SC, without IV induction. Clinical response and clinical remission were both assessed 16 weeks after treatment switch. Endoscopic response and endoscopic remission were assessed at Wks 96 and 144 (definitions in Figure). Safety was assessed through Wk 144.

Results: In total, 17 pts treated with UST underwent treatment switch to continuing GUS 200 mg q4w SC maintenance therapy due to meeting inadequate treatment response criteria between Wks 52-80 of the LTE. Pts who crossed over to GUS exhibited similar baseline demographics and disease characteristics to all GUS LTE pts (Table).

The proportions of pts achieving clinical response and clinical remission 16 weeks after treatment adjustment from UST to GUS 200 mg SC q4w were 58.8% and 52.9%, respectively. The proportions of pts achieving endoscopic response and endoscopic remission were 52.9% and 35.3% at study Wk 96, respectively, and were maintained through Wk 144 (Figure).

Key safety event rates through Wk 144 were consistent with the known safety profile of GUS in approved indications.

Discussion: Among pts who experienced inadequate response to UST in LTE, more than half achieved clinical remission 16 weeks after treatment adjustment to GUS 200 mg SC q4w and >50% were in endoscopic response at Wk 96. These data suggest pts with an inadequate treatment response to UST may benefit from GUS treatment. Results are limited by small sample size and direct treatment adjustment to GUS SC maintenance dosing without IV induction.

Figure: Figure. Clinical Response and Remission 16 Weeks After Switch From Ustekinumab to Guselkumab (A), and Endoscopic Outcomes at Study Weeks 96 and 144 Among Participants Who Switched From Ustekinumab to Guselkumab (B)

Note: The table for this abstract can be viewed in the ePoster Gallery section of the ACG 2024 ePoster Site or in The American Journal of Gastroenterology's abstract supplement issue, both of which will be available starting October 27, 2024.

Disclosures:

Anita Afzali: AbbVie – Consultant. Bristol Myers Squibb/Celgene – Consultant. Cullgen – Consultant. DiaSorin – Consultant. Eli Lilly – Consultant. Gilead – Consultant. IBD Horizons – Consultant. Janssen – Consultant. Pfizer – Consultant. Takeda – Consultant. TLL Pharmaceuticals – Consultant.

Douglas Wolf: AbbVie – Consultant. Bristol Myers Squibb – Consultant. Janssen – Consultant. Lilly – Consultant. Pfizer – Consultant. Takeda – Consultant.

Rupert Leong: AbbVie – Advisory Committee/Board Member. Aspen – Advisory Committee/Board Member. BMS – Advisory Committee/Board Member. Celgene – Advisory Committee/Board Member. Celltrion – Advisory Committee/Board Member, Grant/Research Support. Chiesi – Advisory Committee/Board Member. Ferring – Advisory Committee/Board Member. Gastroenterological Society of Australia – Grant/Research Support. Glutagen – Advisory Committee/Board Member. Gutsy Group – Grant/Research Support. Hospira – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member, Grant/Research Support. Lilly – Advisory Committee/Board Member. McCusker Charitable Trust – Grant/Research Support. MSD – Advisory Committee/Board Member. NHMRC – Grant/Research Support. Novartis – Advisory Committee/Board Member. Pfizer – Advisory Committee/Board Member, Grant/Research Support. Prometheus Biosciences – Advisory Committee/Board Member. Shire – Grant/Research Support. Takeda – Advisory Committee/Board Member, Grant/Research Support. University of Sydney – Joanna Tiddy grant.

Leonardo Salese: Johnson & Johnson – Employee, Stock Options, Stock-publicly held company(excluding mutual/index funds).

Long-Long Gao: Johnson & Johnson – Employee, Stock Options, Stock-publicly held company(excluding mutual/index funds).

Christopher Busse: Johnson & Johnson – Employee, Stock Options, Stock-publicly held company(excluding mutual/index funds).

Julián Panés: AbbVie – Consultant, Honorarium. Alimentiv – Advisory Committee/Board Member, Consultant, Honorarium. Athos – Consultant, Honorarium. Atomwise – Consultant, Honorarium. Boehringer Ingelheim – Consultant, Honorarium. Celsius – Consultant, Honorarium. Ferring – Consultant, Honorarium. Galapagos – Consultant, Honorarium. Genentech/Roche – Consultant, Honorarium. GlaxoSmithKline – Consultant, Honorarium. Janssen – Consultant, Honorarium. Mirum – Advisory Committee/Board Member, Consultant, honorarium. Nimbus – Consultant, Honorarium. Pfizer – Consultant, Honorarium. Progenity – Consultant, Honorarium. Prometheus – Consultant, Honorarium. Protagonist – Consultant, Honorarium. Revolo – Consultant, Honorarium. Sanofi – Advisory Committee/Board Member, Consultant, Honorarium. Sorriso – Advisory Committee/Board Member, Consultant, Honorarium. Surrozen – Advisory Committee/Board Member, Consultant, Honorarium. Takeda – Consultant, Honorarium. Wasserman – Consultant, Honorarium.

Anita Afzali, MD, MPH, MHCM, FACG¹, Douglas Wolf, MD², Rupert Leong, MBBS, MD³, Leonardo Salese, MD⁴, Long-Long Gao, PhD⁵, Christopher Busse, MS⁶, Julián Panés, MD⁷. P4333 - Efficacy and Safety of Subcutaneous Guselkumab Rescue Therapy in Patients With Moderately to Severely Active Crohn’s Disease and Inadequate Response to Ustekinumab: Phase 2 GALAXI 1 Study Long-Term Extension Results, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.