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Poster Session B - Monday Morning

B0417 - Efficacy and Safety of Upadacitinib Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Final Results From the Phase 3 U-ACHIEVE Maintenance Study

Monday, October 24, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

WZ

Wen Zhou, MD, PhD

AbbVie Inc.
North Chicago, IL

Séverine Vermeire, MD, PhD¹, Silvio Danese, MD, PhD², Wen Zhou, MD, PhD³, Xuan Yao, PhD⁴, Dapo Ilo, MBBS, MRCS, MSc⁴, John Liu, MD, MS⁴, Xavier Hébuterne, MD⁵, James Lindsay, DO⁶, Yuri Sanchez-Gonzalez, PhD⁴, Peter D. Higgins, MD, PhD, MSc⁷, Jean-Frederic Colombel, MD⁸, Remo Panaccione, MD⁹
¹University Hospitals Leuven, Leuven, Brussels Hoofdstedelijk Gewest, Belgium; ²IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Molise, Italy; ³AbbVie Inc., North Chicago, IL; ⁴AbbVie, Inc., North Chicago, IL; ⁵CHU de Nice, Université Côte d’Azur, Nice, Provence-Alpes-Cote d'Azur, France; ⁶The Royal London Hospital, Barts Health NHS Trust, London, England, United Kingdom; ⁷University of Michigan, Ann Arbor, MI; ⁸Icahn School of Medicine at Mount Sinai, New York, NY; ⁹University of Calgary, Calgary, AB, Canada

Introduction: Upadacitinib(UPA), has shown superior efficacy to placebo(PBO) in patients with moderate to severe active ulcerative colitis(UC) in two Phase 3 induction studies .^1,2 Patients demonstrating clinical response per Adapted Mayo score with UPA 45mg once daily(QD) after 8 weeks(wks) induction were enrolled to U-ACHIEVE Maintenance.

Methods: U-ACHIEVE Maintenance efficacy data from the intent-to-treat(ITT) population, defined as UPA 45mg QD 8wk induction responders enrolled per protocol for 52wk maintenance, and safety data from the safety population, defined as patients who received ≥1 dose of study therapy(ITT plus patients receiving up to 44wksmaintenanceper prior versions of protocol amendments).

Results: In ITT population, 681 patients achieving clinical response after 8wks of induction were re-randomized to UPA 15mg(UPA15; n=225), UPA 30mg (UPA30; n=233), or PBO(n=223) maintenance. A greater proportion of patients achieved primary endpoint of clinical remission at Wk 52 with UPA15(40.4%) and UPA30(53.6%) vs PBO(10.8%; both p< 0.001), and secondary endpoints including endoscopic improvement and remission, maintenance of clinical remission, steroid-free clinical remission, and histologic-endoscopic mucosal improvement(all p< 0.001; Table). Safety evaluation included 746 patients(UPA15, n=250; UPA30, n=251; PBO, n=245). Of these, 8.4% experienced a serious adverse event(AE) with UPA15, 8.4% UPA30, and 9.4% PBO; 4.0%, 7.2%, and 10.2% experienced AEs leading to treatment discontinuation, respectively. The most common AEs were worsening UC with UPA15(11.6%) and PBO(30.2%), and nasopharyngitis with UPA30(10.4%). There were no deaths. Serious infections were reported in 3.6% of UPA15 patients, 2.8% UPA30, and 3.3% PBO. Herpes zoster was reported only with UPA(UPA15, 4.8%; UPA30, 5.6%). Malignancies excluding non-melanoma skin cancer were reported by one patient with PBO and UPA15, and two with UPA30. Major adverse cardiovascular events were reported in one PBO patient and one UPA30(n=0, UPA15), and venous thromboembolic events were reported in two patients each with UPA15 and UPA30(n=0, PBO).

Discussion: In UC patients who responded to induction therapy, both UPA15 and UPA30 were significantly more efficacious vs PBO as maintenance across primary and secondary endpoints. UPA doses were well tolerated, and there were no new safety signals with a larger population than previously reported.³ These results are consistent with previously published data.³

Primary and key secondary endpoints at Week 52

PBO, n (%) [N]

N=223

UPA 15 mg QD,

n (%) [N]

N=225

Adjusted difference vs PBO, % (95% CI)a

UPA 30 mg QD,

n (%) [N]

N=233

Adjusted difference vs PBO, % (95% CI)a

Primary endpoint:

Clinical remissionb

24 (10.8)

91 (40.4)

30.1***

(22.7, 37.4)

125 (53.6)

42.9***

(35.4, 50.4)

Maintenance of clinical responsec

44 (21.5)

[N=204]

129 (65.6)

[N=197]

43.9***

(35.4, 52.5)

168 (77.5)

[N=217]

55.6***

(47.8, 63.4)

Endoscopic improvementd

31 (14.1)

109 (48.5)

34.4***

(26.7, 42.1)

147 (63.3)

49.0***

(41.4, 56.7)

Maintenance of clinical remissione

16 (18.8)

[N=85]

41 (53.6)

[N=76]

34.9***

(21.2, 48.5)

57 (65.8)

[N=87]

46.9***

(34.0, 59.8)

Corticosteroid-free clinical remissionf

16 (18.8)

[N=85]

40 (52.3)

[N=76]

33.7***

(20.0, 47.3)

56 (64.6)

[N=87]

45.5***

(32.6, 58.5)

Maintenance of endoscopic improvementg

21 (18.4)

[N=115]

59 (61.2)

[N=97]

42.2***

(30.4, 53.9)

84 (71.0)

[N=118]

51.5***

(40.9, 62.1)

Endoscopic remissionh

14 (6.1)

56 (24.9)

18.6***

(12.2, 25.0)

66 (28.3)

21.9***

(15.4, 28.5)

Histologic-endoscopic mucosal improvementi

Mucosal healingj

27 (12.3)

11 (5.1)

91 (40.5)

42 (18.8)

28.5***

(21.1, 35.9)

13.5***

(7.8, 19.3)

131 (56.0)

53 (22.6)

43.8***

(36.1, 51.5)

17.2***

(11.2, 23,3)

***p< 0.001. The efficacy analysis was performed in patients who received up to 52 weeks’ maintenance treatment (ITT population). Non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19 was used.

aBased on adjusted Cochran–Mantel–Haenszel test adjusted for strata (corticosteroid use at Week 0 (yes or no), clinical remission status at Week 0 (yes or no), biologic-IR status at baseline (biologic-IR or non-biologic-IR)).

bPer Adapted Mayo score ≤2: stool frequency subscore ≤1 and not greater than induction baseline, RBS=0, and ES ≤1.

cMaintenance of clinical response, defined as a decrease in Adapted Mayo score ≥2 and ≥30% from induction baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1, at Week 52 among patients who achieved clinical response at the end of the induction therapy.

dES ≤1.

eMaintenance of CR at Week 52 among patients with CR at the end of the induction therapy.

fCR at Week 52 and corticosteroid-free for ≥90 days prior to Week 52 among patients with CR at the end of the induction therapy.

gEndoscopic improvement at Week 52 among patients with endoscopic improvement at the end of the induction therapy.

hES=0.

iES ≤1 and Geboes score ≤3.1.

jES=0 and Geboes score < 2.0.

CI, confidence interval; CR, clinical remission; ES, endoscopic subscore; IR, inadequate responders; ITT, intent-to-treat; PBO, placebo; QD, once daily; RBS, rectal bleeding subscore; UPA, upadacitinib

Disclosures:

Séverine Vermeire: AbbVie – Consultant, Grant/Research Support. Arena – Consultant. Celgene – Consultant. Eli Lilly – Consultant. Ferring – Consultant. Galapagos – Consultant. Genentech/Roche – Consultant. Gilead – Consultant. Hospira – Consultant. Janssen – Consultant. Johnson & Johnson – Grant/Research Support. MSD – Consultant. Mundipharma – Consultant. Pfizer – Consultant, Grant/Research Support. Progenity – Consultant. Second Genome – Consultant. Shire – Consultant. Takeda – Consultant, Grant/Research Support.

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.

Wen Zhou: AbbVie – Employee, Stock Options.

Xuan Yao: AbbVie – Employee, Stock Options.

Dapo Ilo: AbbVie – Employee, Stock Options.

John Liu: AbbVie – Employee, Stock Options.

Xavier Hébuterne: AbbVie – Advisor or Review Panel Member, Grant/Research Support, Speakers Bureau. Abivax – Grant/Research Support. Amgen – Speakers Bureau. Arena Pharmaceuticals – Advisor or Review Panel Member, Grant/Research Support. Baxter – Speakers Bureau. Celgene – Grant/Research Support. Eli Lilly – Grant/Research Support. Enterome – Grant/Research Support. Fresenius Kabi – Speakers Bureau. Galapagos – Advisor or Review Panel Member, Grant/Research Support, Speakers Bureau. InDex Pharmaceuticals – Grant/Research Support. Janssen – Advisor or Review Panel Member, Grant/Research Support, Speakers Bureau. MSD – Speakers Bureau. Mylan – Speakers Bureau. Nestlé Health Science – Advisor or Review Panel Member. Nutricia – Speakers Bureau. Pfizer – Advisor or Review Panel Member, Grant/Research Support, Speakers Bureau. Roche – Advisor or Review Panel Member, Grant/Research Support. Salix – Grant/Research Support. Sangamo – Grant/Research Support. Takeda – Advisor or Review Panel Member, Grant/Research Support, Speakers Bureau. Theravance – Grant/Research Support. Tillots Pharma – Speakers Bureau. Viatrris – Speakers Bureau.

James Lindsay: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Allergan – Advisory Committee/Board Member, Consultant, Speakers Bureau. Atlantic Healthcare – Advisory Committee/Board Member, Consultant. Bristol-Myers Squibb(BMS) – Advisory Committee/Board Member, Consultant. Celgene – Advisory Committee/Board Member, Consultant. Celltrion – Advisory Committee/Board Member, Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Ferring Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speakers Bureau. Gilead – Advisory Committee/Board Member, Consultant, Grant/Research Support. GlaxoSmithKlein(GSK) – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. MSD – Advisory Committee/Board Member, Consultant, Speakers Bureau. Napp – Advisory Committee/Board Member, Consultant, Speakers Bureau. Norgine – Speakers Bureau. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Shire – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Tillots Pharma – Speakers Bureau. Vifor Pharma – Advisory Committee/Board Member, Consultant.

Yuri Sanchez-Gonzalez: AbbVie – Employee, Stock Options.

Peter Higgins: AbbVie – Consultant. Amgen – Consultant. Eli Lilly – Consultant. Gastrointestinal Health Foundation – Consultant. Genentech – Consultant. Imedex – Consultant. JBR Pharma – Consultant. Lycera – Consultant. National Institutes of Health – Grant/Research Support. Pfizer – Consultant. Takeda – Consultant, Grant/Research Support. The Crohn’s & Colitis Foundation – Grant/Research Support. Vindico Medical Education – Consultant.

Jean-Frederic Colombel: AbbVie – Consultant, Grant/Research Support. Amgen – Consultant. Arena – Consultant. BMS – Consultant. Boehringer Ingelheim – Consultant. Celgene Corporation – Consultant. Celltrion – Personal Fees. Eli Lilly – Consultant. Enterome – Personal Fees. Ferring Pharmaceuticals – Consultant. Galmed Research – Consultant. Galxo Smith Kline – Consultant. Genentech – Consultant. Genfit – Stock Options. Imedex – Consultant. Immunic – Consultant. Intestinal Biotech Development – Stock Options. Intestinal Biotech Development – Stock Options. Iterative Scopes – Consultant. Janssen Pharmaceuticals – Advisory Committee/Board Member, Consultant, Grant/Research Support. Kaleido Biosciences – Consultant. MedImmune – Personal Fees. Merck – Consultant. Microba – Consultant. Novartis – Consultant. PBM Capital – Consultant. Pfizer – Consultant. PPM Services – Personal Fees. Protagonist Therapeutics – Consultant. Sanofi – Consultant. Second Genome – Personal Fees. Seres – Personal Fees. Shire – Personal Fees. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support. Theradiag – Personal Fees. TiGenix – Consultant. Vifor – Consultant.

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.