40 - Induction Combination Therapy With Guselkumab and Golimumab Followed by Guselkumab Monotherapy Maintenance: Results of the Phase 2a, Randomized, Double-Blind, Proof-of-Concept VEGA Study

Tuesday, October 25, 2022

2:45 PM – 2:55 PM ET

Location: Hall C2

Presenting Author(s)

Brian G. Feagan, MD

Alimentiv, Inc.; Western University
London, ON, Canada

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Brian G. Feagan, MD¹, Bruce E. Sands, MD, MS, FACG², William J. Sandborn, MD³, Matthew Germinaro, MD⁴, Marion Vetter, MD⁵, Shihong Sheng, PhD⁴, Jewel Johanns, PhD⁴, Julian Panés, MD⁶
¹Alimentiv, Inc.; Western University, London, ON, Canada; ²Icahn School of Medicine at Mount Sinai, New York, NY; ³University of California San Diego, La Jolla, CA; ⁴Janssen Research & Development, LLC., Spring House, PA; ⁵Janssen Research & Development, LLC, Spring House, PA; ⁶Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain

Introduction: Week (wk) 12 data from the VEGA study demonstrated that dual blockade of interleukin (IL)-23 and TNFα more effectively induced clinical response, clinical remission, endoscopic improvement, and composite histologic-endoscopic outcomes than either monotherapy alone. The efficacy and safety of combination induction therapy with guselkumab (GUS) + golimumab (GOL) followed by GUS monotherapy for maintenance (combination GUS) vs GUS or GOL alone were evaluated through wk38 in adults with moderately-to-severely active UC.

Methods: 214 patients (pts) naïve to TNFα antagonists and refractory or intolerant to conventional therapy were randomized to receive GUS 200mg intravenous (IV) at wks0, 4, and 8 100mg subcutaneous (SC) every 8 wks (q8w) (n=71); GOL 200mg subcutaneous (SC) at wk0 then 100mg SC at wk2 and q4w thereafter (n=72); or combination therapy with GUS 200mg IV+GOL 200mg SC at wk0, GOL 100mg SC at wks2, 6, and 10, and GUS 200mg IV at wks4 and 8 followed by GUS 100 mg SC q8w (n=71). After wk12, pts randomized to monotherapy continued treatment through the final efficacy assessment at wk38, while pts randomized to the combination group transitioned to maintenance GUS. Clinical, endoscopic, histologic, and composite histologic-endoscopic endpoints were assessed. Safety was assessed through the final safety visit (up to wk50 or 16 wks after the final dose of study intervention).

Results: Overall, 13.1% of pts discontinued treatment prior to wk34 (final dose of study intervention). Clinical remission rates (based on the full Mayo score) at wk38 in the combination GUS group (43.7%) were greater than the GUS and GOL monotherapy groups (31.0% and 22.2%, respectively, Table). Rates of clinical remission by modified Mayo (mMayo) score components, endoscopic improvement, endoscopic normalization, histologic remission, and composite histologic-endoscopic endpoints at wk38 were also greater in the combination GUS group than the GUS or GOL monotherapy groups. GUS monotherapy resulted in greater rates of clinical, endoscopic, and histologic outcomes than GOL monotherapy at wk38. Adverse event (AE), serious AE, infection, and serious infection rates were comparable among treatment groups through the final safety visit.

Discussion: Pts who received combination GUS treatment maintained greater rates of clinical remission, endoscopic improvement, endoscopic normalization, and both histologic remission and endoscopic improvement at wk38 than those who received GUS or GOL monotherapy.

a. The adjusted treatment difference between the combination therapy vs. the monotherapy groups and the confidence interval were based on the Wald statistic with the Cochran-Mantel-Haenszel (CMH) weight. b. The p-value was based on the 2-sided CMH chi-square test, stratified by corticosteroid use at baseline (Yes, No). All P-values are nominal. c. Pts who had an ostomy or colectomy, had a protocol-prohibited change in concomitant UC medications, or discontinued study intervention due to lack of a therapeutic effect or an adverse event of worsening UC, or discontinued study agent early due to COVID-19 related reasons (excluding COVID-19 infection) prior to the wk 38 visit were considered to not have achieved the binary endpoints. Pts with missing data at wk 38 were considered to not have achieved the binary endpoints. d. Clinical remission is defined as Mayo score ≤2, with no individual subscore >1. e. Clinical remission (based on the mMayo) is defined as a stool frequency subscore of 0 or 1, where the stool frequency subscore has not increased from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on endoscopy. f. Symptomatic remission is defined as Mayo stool frequency subscore of 0 or 1, where the stool frequency subscore has not increased from baseline, and a rectal bleeding subscore of 0. g. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1 with no friability present on the endoscopy. h. Endoscopic normalization is defined as an endoscopy subscore of 0. i. Histologic remission is defined as absence of neutrophils from the mucosa (both lamina propria and epithelium), no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system.
Outcome, n (%)	GOL (N=72)	GUS (N=71)	Combination→GUS (N=71)	Δ (80% CI)^a P-value^b Combination→GUS vs. GOL	Δ (80% CI)^a P-value^b Combination→GUS vs. GUS
Clinical remission^c,d	16 (22.2)	22 (31.0)	31 (43.7)	21.5 (11.9, 31.2) 0.006	12.7 (2.7, 22.7) 0.109
Clinical remission (based on mMayo)^c,e	15 (20.8)	22 (31.0)	34 (47.9)	27.1 (17.7, 36.6) < 0.001	16.9 (7.0, 26.8) 0.033
Symptomatic remission^c,f	43 (59.7)	49 (69.0)	49 (69.0)	9.4 (-0.6, 19.4) 0.238	0.0 (-9.7, 9.7) 1.000
Endoscopic improvement^c.g	16 (22.2)	23 (32.4)	35 (49.3)	27.2 (17.6, 36.7) < 0.001	16.9 (7.0, 26.8) 0.033
Endoscopic normalization^c,h	5 (6.9)	11 (15.5)	18 (25.4)	18.5 (11.1, 25.9) 0.002	9.9 (1.6, 18.2) 0.134
Histologic remission^c,i	18 (25.0)	29 (40.8)	36 (50.7)	25.8 (16.1, 35.5) 0.001	9.9 (-0.4, 20.1) 0.224
Both histologic remission and endoscopic improvement^c,g,i	10 (13.9)	15 (21.1)	30 (42.3)	28.5 (19.6, 37.4) < 0.001	21.1 (11.8, 30.5) 0.005
Both histologic remission and endoscopic normalization^c,h,i	4 (5.6)	9 (12.7)	17 (23.9)	18.5 (11.3, 25.6) 0.002	11.3 (3.3, 19.2) 0.074

Table: Table. Efficacy at wk 38; intent-to-treat population

Disclosures:

Brian Feagan: AbbVie – Consultant, Member of the scientific advisory board, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Alimentiv Inc – Consultant. Allianthera – Consultant. Amgen – Consultant, Member of the scientific advisory board. AnaptysBio – Consultant. Applied Molecular Transport Inc. – Consultant. Arena Pharma – Consultant. Avir – Consultant. Azora Therapeutics – Consultant. BioJamp – Consultant. Biopharma – Consultant. Biora Therapeutics – Consultant. Boehringer-Ingelheim – Consultant, Member of scientific advisory board. Boston Pharma – Consultant. Boxer – Consultant. Celgene/BMS – Consultant, Member of scientific advisory board. Connect BioPharma – Consultant. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 Capital – Consultant, Member of the scientific advisory board. Eli Lilly and Company – Consultant. Equillium – Consultant. Ermium – Consultant. Everest Clinical Research Corp. – Consultant. Ferring – Consultant. First Wave – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Consultant, Member of scientific advisory board. Gilead – Consultant. Glenmark – Consultant. Gossamer Pharma – Consultant, Stock Shareholder. GSK – Consultant, Member of the scientific advisory board. Hoffmann-LaRoche – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. ImmunExt – Consultant. Immunic Therapeutics – Consultant. Index Pharma – Consultant, Member of the scientific advisory board. Intact Therapeutics – Consultant. JAKAcademy – Consultant. Janssen – Consultant, Member of scientific advisory board, Speakers Bureau. Japan Tobacco Inc. – Consultant. Kaleido Biosciences – Consultant. L.E.K. Consulting – Consultant. Landos Biopharma – Consultant. Leadiant – Consultant. LifeSci Capital – Consultant. Lument AB – Consultant. Millennium – Consultant. MiroBio – Consultant. Morphic Therapeutics – Consultant, Member of the scientific advisory board. Mylan – Consultant. Novartis – Member of the scientific advisory board. OM Pharma – Consultant. Origo BioPharma – Consultant, Member of scientific advisory board. Orphagen – Consultant. Otsuka – Consultant. Pandion Therapeutics – Consultant. Pfizer – Consultant, Member of the scientific advisory board. Play to Know AG – Consultant. Progenity – Consultant, Member of the scientific advisory board. Prometheus – Member of scientific advisory board. Prometheus Therapeutics and Diagnostics – Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. RedHill – Consultant. REDX – Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Consultant, Member of the scientific advisory board, Speakers Bureau. Teva – Consultant, Member of the scientific advisory board. Thelium – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Consultant, Member of the scientific advisory board. UCB Pharma – Consultant. VHsquared Ltd. – Consultant. Viatris – Consultant. Western University – Employee. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.

Bruce Sands: Abivax – Consultant, Speaking. Amgen – Consultant. Arena Pharmaceuticals – Consultant. Artugen Therapeutics – Consultant. AstraZeneca – Consultant. Bacainn Therapeutics – Consultant. Boehringer-Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, speaking, research funding. Calibr – Consultant. Celltrion Healthcare – Consultant. ClostraBio – Consultant. Eli Lilly and Company – Consultant. Entera – Consultant. Evommune – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. InDex Pharmaceuticals – Consultant. Innovation Therapeutics – Consultant. Inotrem – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Consultant, Grant/Research Support, speaking. Kaleido – Consultant. Kallyope – Consultant. Miro Bio – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. Pfizer – Consultant, speaking. Progenity – Consultant. Prometheus Biosciences – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. Surrozen – Consultant. Takeda – Consultant, Speaking. Teva – Consultant. TLL Pharmaceutical – Consultant. USWM Enterprises – Consultant. VielaBio – Consultant.

William Sandborn: AbbVie – Consultant, Grant/Research Support. Abivax – Consultant. Admirx – Consultant. Alfa sigma – Consultant. Alimentiv (previously Robarts Clinical Trials, owned by Alimentiv Health Trust) – Consultant. Alivio Therapeutics – Consultant. Allakos – Consultant, Stock Options. Allergan – Consultant. Amgen – Consultant. Applied Molecular Transport – Consultant. Arena Pharmaceuticals – Consultant, Grant/Research Support. Avexegen Therapeutics – Consultant. Aviva – Grant/Research Support. Bausch Health (Salix) – Consultant. BeiGene – Consultant, Stock Options. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant, Grant/Research Support. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant, Grant/Research Support. Celltrion – Consultant. Cellularity – Consultant. Conatus – Consultant. Cosmo Pharmaceuticals – Consultant. Equillium – Consultant. Escalier Biosciences – Consultant. Ferring – Consultant. Forbion – Consultant. Genentech – Grant/Research Support. Genentech/Roche – Consultant. Gilead Sciences – Consultant, Grant/Research Support. Glenmark Pharmaceuticals – Consultant. Gossamer Bio – Consultant, Stock Options. GSK – Grant/Research Support. Immunic (Vital Therapies) – Consultant. Incyte – Consultant. Index Pharmaceuticals – Consultant. Intact Therapeutics – Consultant. Janssen – Consultant, Grant/Research Support. Kyowa Kirin Pharmaceutical Research – Consultant. Kyverna Therapeutics – Consultant. Landos Biopharma – Consultant. Lilly – Consultant, Grant/Research Support. Miraca Life Sciences – Consultant. Nivalis Therapeutics – Consultant. Novartis – Consultant. Nutrition Science Partners – Consultant. Oppilan Pharma (acquired by Ventyx Biosciences) – Consultant, Stock Options. Otsuka – Consultant. Pandion Therapeutics – Consultant. Paul Hastings – Consultant. Pfizer – Consultant, Grant/Research Support. Progenity – Consultant, Stock Options. Prometheus Biosciences – Consultant, Grant/Research Support, Stock Options. Prometheus Laboratories – Consultant, Stock Options. Protagonist Therapeutics – Consultant. Provention Bio – Consultant. Reistone Biopharma – Consultant. Ritter Pharmaceuticals – Consultant. Seres Therapeutics – Consultant, Grant/Research Support. Shanghai Pharma Biotherapeutics – Consultant. Shire – Consultant, Grant/Research Support. Shoreline Biosciences – Consultant, Employee, Stock Options. Sienna Biopharmaceuticals – Consultant. Sigmoid Biotechnologies – Consultant. Sterna Biologicals – Consultant. Sublimity Therapeutics – Consultant. Surrozen – Consultant. Takeda – Consultant, Grant/Research Support. TheraVance Biopharma – Consultant, Grant/Research Support. Thetis Pharmaceuticals – Consultant. Tigenix – Consultant. Tillotts Pharma – Consultant. UCB Pharma – Consultant. Vendata Biosciences – Consultant. Ventyx Biosciences – Consultant, Stock Options. Vimalan Biosciences – Consultant, Stock Options. Vivelix Pharmaceuticals – Consultant. Vivreon Biosciences – Consultant, Stock Options. Zealand Pharma – Consultant.

Matthew Germinaro: Janssen Research & Development – Employee. Johnson & Johnson – Stock-publicly held company(excluding mutual/index funds).

Marion Vetter: Janssen Research & Development – Employee. Johnson & Johnson – Stock-publicly held company(excluding mutual/index funds).

Shihong Sheng: Janssen Research & Development – Employee. Johnson & Johnson – Stock-publicly held company(excluding mutual/index funds).

Jewel Johanns: Janssen Research & Development – Employee. Johnson & Johnson – Stock-publicly held company(excluding mutual/index funds).

Julian Panés: Abbott – payment for the development of educational presentations, Speakers Bureau. AbbVie – Consultant, Grant/Research Support, support for travel to meetings, during the conduct of the study; payment for development of educational presentations. Arena – Consultant. Athos – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Celltrion – Consultant. Ferring – Consultant. Galapagos – Consultant. Genentech-Roche – Consultant. GSK – Consultant. Janssen – Consultant, Payment for development of educational presentations, Speakers Bureau. Mirum – Consultant. Morphic – Consultant. MSD – Consultant. Nestlé – Consultant. Origo – Consultant. Pandion – Consultant. Pfizer – Consultant, Grant/Research Support, Payment for development of educational presentations, Speakers Bureau. Progenity – Consultant. Protagonist – Consultant. Revolo – Consultant. Robarts – Consultant. Roche – Payment for development of educational presentations. Takeda – Consultant, Support for travel to meetings during the conduct of the study, Speakers Bureau. Theravance – Consultant, Speakers Bureau. Wassermann – Consultant.

Brian G. Feagan, MD¹, Bruce E. Sands, MD, MS, FACG², William J. Sandborn, MD³, Matthew Germinaro, MD⁴, Marion Vetter, MD⁵, Shihong Sheng, PhD⁴, Jewel Johanns, PhD⁴, Julian Panés, MD⁶, 40, Induction Combination Therapy With Guselkumab and Golimumab Followed by Guselkumab Monotherapy Maintenance: Results of the Phase 2a, Randomized, Double-Blind, Proof-of-Concept VEGA Study, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.