38 - 52-Week Risankizumab Subcutaneous Maintenance Dosing Is Efficacious and Well Tolerated in Patients With Moderate to Severe Crohn’s Disease Who Had Delayed Response to 12-Weeks IV Risankizumab Induction

Tuesday, October 25, 2022

2:25 PM – 2:35 PM ET

Location: Hall C2

Presenting Author(s)

Marla Dubinsky, MD

Icahn School of Medicine
Mount Sinai, NY

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Geert D’Haens, MD¹, Remo Panaccione, MD², Julian Panés, MD, PhD³, Tadakazu Hisamatsu, MD, PhD⁴, Peter Bossuyt, MD⁵, Silvio Danese, MD, PhD⁶, Ezequiel Neimark, MD⁷, Alexandra Song, MD⁷, Xiaomei Liao, PhD⁷, Kori Wallace, MD, PhD⁷, Javier Zambrano, MD⁷, W Rachel Duan, PhD⁷, Kristina Kligys, PhD⁷, Marla Dubinsky, MD⁸
¹Amsterdam University Medical Centres, Amsterdam, Zuid-Holland, Netherlands; ²University of Calgary, Calgary, AB, Canada; ³Formerly, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain; ⁴Kyorin University School of Medicine, Tokyo, Tokyo, Japan; ⁵Imelda General Hospital, Bonheiden, Brussels Hoofdstedelijk Gewest, Belgium; ⁶IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Molise, Italy; ⁷AbbVie, Inc., North Chicago, IL; ⁸Icahn School of Medicine, Mount Sinai, NY

Introduction: In patients with moderate to severe Crohn's disease (CD), the ADVANCE and MOTIVATE phase 3 induction studies showed intravenous (IV) risankizumab (RZB), an anti-p19 interleukin-23 inhibitor, to be superior to placebo (PBO) for achieving clinical and endoscopic endpoints at Week (Wk) 12.¹ Here, we evaluated the long-term efficacy and safety of RZB during the FORTIFY maintenance study in patients with delayed clinical response to IV RZB induction.

Methods: Patients who did not achieve clinical response (defined as ≥30% decrease in average daily stool frequency [SF] and/or ≥30% decrease in average daily abdominal pain score [APS], both not worse than baseline of induction) following 12-wks IV RZB (600 mg or 1200 mg) induction dosing, but who did achieve clinical response at Wk 24 following an additional 12-wks RZB subcutaneous (SC) dosing (“delayed responders”) were examined. These patients continued on the same dose (RZB 180 mg SC [N = 30], RZB 360 mg SC [N = 33]) in the FORTIFY maintenance study and were analyzed for clinical and endoscopic improvements at Wk 52.

Results: At FORTIFY Wk 52, most delayed responders achieved clinical remission and response with 180 mg or 360 mg RZB SC (Table, see footnotes for endpoint definitions). In addition, patients receiving RZB SC (180 mg or 360 mg) also achieved endoscopic response (36.7%, 45.5%), endoscopic remission (40.0%, 42.4%), deep remission (40.0%, 39.4%), ulcer free endoscopy (27.6%, 24.2%), and the combined endpoint of SF/APS clinical remission + endoscopic response (23.3%, 36.4%). Moreover, a dose-response trend was observed, with numerically higher response rates observed with RZB 360 mg SC relative to 180 mg SC for most outcomes, including clinical remission (CDAI and SF/APS), CDAI clinical response, enhanced clinical response, endoscopic response, endoscopic remission, and the composite endpoint of SF/APS clinical remission + endoscopic response. SC RZB maintenance dosing in delayed responders was well tolerated. The profile of treatment emergent adverse events was consistent with the known safety profile of patients with CD treated with RZB. No new safety risks were identified.

Discussion: RZB was efficacious in patients with delayed clinical response to RZB induction. These findings underscore the additional clinical benefit of SC RZB treatment in maintenance, even in patients who were initial non-responders to 12-wks IV RZB induction. RZB was well tolerated in delayed responders with no new safety risks identified.

Responder Group Treatment Group, n (%) [95% CI]	CDAI Clinical Response	Enhanced Clinical Response	CDAI Clinical Remission	SF/APS Clinical Remission	Endoscopic Response	Ulcer Free Endoscopy	Endoscopic Remission	SF/APS Clinical Remission and Endoscopic Response	Deep Remission
RZB 180 mg SC delayed responders, Wk 24	53.3 (6/30) [35.5, 71.2]	56.7 (17/30) [38.9, 74.4]	53.3 (16/30) [35.5, 71.2]	43.3 (13/30) [25.6, 61.1]	36.7 (11/30) [19.4, 53.9]	27.6 (8/29) [11.3, 43.9]	40.0 (12/30) [22.5, 57.5]	23.3 (7/30) [8.2, 38.5]	40.0 (12/30) [22.5, 57.5]
RZB 360 mg SC delayed responders, Wk 24	75.8 (25/33) [61.1, 90.4]	66.7 (22/33) [50.6, 82.8]	66.7 (22/33) [50.6, 82.8]	54.5 (18/33) [37.6, 71.5]	45.5 (15/33) [28.5, 62.4]	24.2 (8/33) [9.6, 38.9]	42.4 (14/33) [25.6, 59.3]	36.4 (12/33) [20.0, 52.8]	39.4 (13/33) [22.7, 56.1]
Responder Group Treatment Group, (E/100PYs)	Deaths	Serious infections	All treatment emergent adverse events	AE related to COVID-19	Serious AE	Hepatic events	Injection site reactions	AE leading to discontinuation of study drug	Crohn's Disease
RZB 180 mg SC (N=31) (PYs=27.5) delayed responders, Wk 24	0	0	132 (479.8)	0	6 (21.8)	0	6 (21.8)	2 (7.3)	7 (25.4)
RZB 360 mg SC (N=33) (PYs=32.1) delayed responders, Wk 24	0	1 (3.1)	83 (258.9)	0	4 (12.5)	1 (3.1)	2 (6.2)	0	7 (21.8)

Table: Table. Efficacy and Safety after 52-Weeks Maintenance SC RZB Dosing in Delayed Responders (NRI-NCa)

Disclosures:

Geert D’Haens: AbbVie – Advisor or Review Panel Member, Speakers Bureau. Ablynx – Advisor or Review Panel Member. Allergan – Advisor or Review Panel Member. Alphabiomics – Advisor or Review Panel Member. AM Pharma – Advisor or Review Panel Member. Amakem – Advisor or Review Panel Member. Amgen – Advisor or Review Panel Member. Arena Pharmaceuticals – Advisor or Review Panel Member. AstraZeneca – Advisor or Review Panel Member. Avaxia – Advisor or Review Panel Member. Biogen – Advisor or Review Panel Member, Speakers Bureau. Boehringer-Ingelheim – Advisor or Review Panel Member. Bristol-Myers Squibb(BMS) – Advisor or Review Panel Member. Celgene/Receptos – Advisor or Review Panel Member. Celltrion – Advisor or Review Panel Member. Cosmo – Advisor or Review Panel Member. Dr FALK Pharma – Advisor or Review Panel Member. Echo Pharmaceuticals – Advisor or Review Panel Member. Eli Lilly – Advisor or Review Panel Member. Engene – Advisor or Review Panel Member. Ferring – Advisor or Review Panel Member, Speakers Bureau. Galapagos – Advisor or Review Panel Member. Genentech/Roche – Advisor or Review Panel Member. Gilead – Advisor or Review Panel Member. GlaxoSmithKlein(GSK) – Advisor or Review Panel Member. Gossamerbio – Advisor or Review Panel Member. Hospira – Advisor or Review Panel Member. Immunic – Advisor or Review Panel Member. Johnson & Johnson – Advisor or Review Panel Member, Speakers Bureau. Kintai Therapeutics – Advisor or Review Panel Member. Lycera – Advisor or Review Panel Member. Medimetrics – Advisor or Review Panel Member. Medtronics – Advisor or Review Panel Member. Merck/MSD – Advisor or Review Panel Member, Speakers Bureau. Millenium/Takeda – Advisor or Review Panel Member, Speakers Bureau. Mitsubishi Pharma – Advisor or Review Panel Member. Mundipharma – Advisor or Review Panel Member, Speakers Bureau. Nextbiotics – Advisor or Review Panel Member. Norgine – Speakers Bureau. Novonordisk – Advisor or Review Panel Member. Otsuka – Advisor or Review Panel Member. Pfizer – Advisor or Review Panel Member, Speakers Bureau. Photopill – Advisor or Review Panel Member. Prodigest – Advisor or Review Panel Member. Progenity – Advisor or Review Panel Member. Prometheus laboratories/Nestle – Advisor or Review Panel Member. Protagonist – Advisor or Review Panel Member. RedHill – Advisor or Review Panel Member. Robarts Clinical Trials – Advisor or Review Panel Member. Salix – Advisor or Review Panel Member. Samsung Bioepis – Advisor or Review Panel Member, Speakers Bureau. Sandoz – Advisor or Review Panel Member. Seres/Nestle – Advisor or Review Panel Member. Setpoint – Advisor or Review Panel Member. Shire – Advisor or Review Panel Member, Speakers Bureau. Teva – Advisor or Review Panel Member. Tigenix – Advisor or Review Panel Member. Tillots Pharma – Advisor or Review Panel Member, Speakers Bureau. Topivert – Advisor or Review Panel Member. Versant – Advisor or Review Panel Member. Vifor Pharma – Advisor or Review Panel Member, Speakers Bureau.

Remo Panaccione: Abbott – Consultant. AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Alimentiv – Consultant. Amgen – Advisory Committee/Board Member, Consultant. Arena – Advisory Committee/Board Member, Consultant, Speakers Bureau. AstraZeneca – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Celgene – Advisory Committee/Board Member, Consultant, Speakers Bureau. Celltrion – Advisory Committee/Board Member, Consultant. Cosmos Pharmaceuticals – Consultant. Eisai – Consultant. Elan – Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant, Speakers Bureau. Ferring – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Galapagos – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant. Gilead Sciences – Advisory Committee/Board Member, Consultant, Speakers Bureau. GlaxoSmithKline – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Merck – Advisory Committee/Board Member, Consultant, Speakers Bureau. Mylan – Advisory Committee/Board Member, Consultant. Oppilan Pharma – Advisory Committee/Board Member, Consultant. Pandion Pharma – Advisory Committee/Board Member. Pandion Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Progenity – Consultant. Protagonist Therapeutics – Consultant. Roche – Consultant, Speakers Bureau. Sandoz – Advisory Committee/Board Member, Consultant, Speakers Bureau. Satisfai Health – Consultant. Schering-Plough – Consultant. Shire – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sublimity Therapeutics – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Theravance – Advisory Committee/Board Member, Consultant. UCB – Consultant.

Julian Panés: AbbVie – Grant/Research Support, Personal fees. Arena – Personal fees. Athos – Personal fees. Boehringer Ingelheim – Personal fees. Celgene – Personal fees. Celltrion – Personal fees. Ferring Pharmaceuticals – Personal fees. Galapagos – Personal fees. Genentech/Roche – Personal fees. GSK – Personal fees. Immunic – Personal fees. Janssen Pharmaceuticals – Personal fees. Mirum – Personal fees. Morphic – Personal fees. Nestlé – Personal fees. Origo – Personal fees. Pandion – Personal fees. Pfizer Inc – Grant/Research Support, Personal fees. Progenity – Personal fees. Takeda – Personal fees. Theravance Biopharma – Personal fees. Wassermann – Personal fees.

Tadakazu Hisamatsu: AbbVie – Consultant, Grant/Research Support, Lecture fees. Celgene – Consultant. Daiichi-Sankyo – Grant/Research Support. EA Pharma Co, Ltd – Consultant, Grant/Research Support, Lecture fees. Janssen Research & Development, LLC – Consultant, lecture fees. JIMRO – Grant/Research Support. JIMRO Co – Consultant, Grant/Research Support. Kyorin Pharmaceutical Co. Ltd – Consultant, Grant/Research Support. Mitsubishi Tanabe Pharma Corporation – Grant/Research Support, Lecture fees. Mochida Pharmaceutical Co., Ltd – Grant/Research Support, lecture fees. Nichi-Iko Pharmaceutical Co., Ltd – Consultant. Nippon Kayaku Co., Ltd – Grant/Research Support. Pfizer Inc – Consultant, Grant/Research Support, lecture fees. Takeda Pharmaceutical Co., Ltd – Grant/Research Support, Lecture fees. Zeria Pharmaceutical Co. Ltd – Grant/Research Support.

Peter Bossuyt: AbbVie – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Amgen – Grant/Research Support. Arena Pharmaceuticals – Advisory Committee/Board Member. Bristol-Myers Squibb(BMS) – Advisory Committee/Board Member. Celltrion – Speakers Bureau. Eli Lilly – Advisory Committee/Board Member. Hospira – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. Merck/MSD – Advisory Committee/Board Member. Mundipharma – Advisory Committee/Board Member, Grant/Research Support. Mylan – Grant/Research Support. Pentax Medical – Advisory Committee/Board Member. Pfizer – Advisory Committee/Board Member, Grant/Research Support, Speakers Bureau. PSI CRO – Advisory Committee/Board Member. Roche – Advisory Committee/Board Member. Sandoz – Advisory Committee/Board Member. Takeda – Advisory Committee/Board Member, Speakers Bureau.

Silvio Danese: AbbVie – Consultant, Speakers Bureau. Allergan – Consultant, Speakers Bureau. Amgen – Consultant, Speakers Bureau. AstraZeneca – Consultant, Speakers Bureau. Athos Therapeutics – Consultant, Speakers Bureau. Biogen – Consultant, Speakers Bureau. Boehringer Ingelheim – Consultant, Speakers Bureau. Celgene – Consultant, Speakers Bureau. Celltrion – Consultant, Speakers Bureau. Eli Lilly – Consultant, Speakers Bureau. Enthera – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. Hospira – Consultant, Speakers Bureau. Inotrem – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. Johnson & Johnson – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Mundipharma – Consultant, Speakers Bureau. Mylan – Consultant, Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Roche – Consultant, Speakers Bureau. Sandoz – Consultant, Speakers Bureau. Sublimity Therapeutics – Consultant, Speakers Bureau. Takeda – Consultant, Lecture fees. TiGenix – Consultant, Speakers Bureau. UCB Inc – Consultant, Speakers Bureau. Vifor – Consultant, Speakers Bureau.

Ezequiel Neimark: AbbVie – Employee, Stock Options.

Alexandra Song: AbbVie – Employee, Stock Options.

Xiaomei Liao: AbbVie – Employee, Stock Options.

Kori Wallace: AbbVie – Employee, Stock Options.

Javier Zambrano: AbbVie – Employee, Stock Options.

W Rachel Duan: AbbVie – Employee, Stock Options.

Kristina Kligys: AbbVie – Employee, Stock Options.

Marla Dubinsky: AbbVie – Consultant. Allergan – Consultant. Amgen – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Eli Lilly – Consultant. Gilead – Consultant. Janssen – Consultant. Pfizer – Consultant. Prometheus Labs – Consultant. Roche – Consultant. Takeda – Consultant. Trellus Health – Share holder. UCB – Consultant.