Efficacy and Safety of a Potent and Highly Selective Oral Tyrosine Kinase 2 Inhibitor, BMS-986165, in Patients with Moderate-to-Severe Plaque Psoriasis: A Phase II, Randomized, Placebo-Controlled Trial

Kim A Papp¹, Kenneth B. Gordon², Diamant Thaçi³, Akimichi Morita⁴, Melinda Gooderham⁵, Peter Foley^6,7,8, Ihab G. Girgis⁹, Sudeep Kundu⁹ and Subhashis Banerjee⁹, ¹Clinical Research and Probity Medical Research, Waterloo, ON, Canada, ²Medical College of Wisconsin, Milwaukee, WI, ³University of Luebeck, Luebeck, Germany, ⁴Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, ⁵SKiN Centre for Dermatology, Queen’s University and Probity Medical Research, Peterborough, ON, Canada, ⁶The University of Melbourne, Melbourne, Australia, ⁷St Vincent’s Hospital Melbourne & Probity Medical Research, Melbourne, Australia, ⁸Skin & Cancer Foundation Inc, Melbourne, Australia, ⁹Bristol-Myers Squibb, Princeton, NJ

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: clinical trials, interleukins (IL), pain, psoriasis and tyrosine kinase inhibition

Session Information

Date: Tuesday, October 23, 2018

Title: Spondyloarthritis Including Psoriatic Arthritis – Clinical Poster III: Treatment

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: BMS-986165, a potent and highly selective oral tyrosine kinase 2 inhibitor, inhibits signal transducer and activator of transcription (STAT)-dependent signalling pathways of interleukin-23 and type I interferons involved in the pathology of immune-mediated diseases. A 12-week (wk), placebo (pbo)-controlled, Phase II, dose-ranging study (ClinicalTrials.gov, NCT02931838) investigated the efficacy and safety of BMS-986165 in patients (pts) with moderate-to-severe plaque psoriasis (PsO). Methods: Adults with PsO for ≥6 months and moderate-to-severe disease (body surface area [BSA] ≥10%, Psoriasis Area and Severity Index [PASI] ≥12, static Physician Global Assessment [sPGA] ≥3) were randomized to pbo or BMS-986165 (3 mg every other day [QOD], 3 mg every day [QD], 3 mg twice daily [BID], 6 mg BID, 12 mg QD). Primary endpoint was PASI 75 at Wk 12. Pain was assessed by ACR pain visual analog scale (VAS). Results: For the 267 pts randomized and treated, baseline characteristics (mean age 45 years, male 73%, median disease duration 15 years, prior biologic experience 43%, mean BSA 23%, mean PASI score 18.0) were generally balanced among treatment arms. At Wk 12, a significantly greater proportion of pts achieved PASI 75, PASI 90 and sPGA 0/1 at doses ≥3 mg QD vs pbo (p<0.05), with dose response observed across all efficacy measures (Table 1). Efficacy was observed in both biologic-naïve and biologic-experienced pts, with rapid onset of response by Day 15. Pain VAS score showed a dose-dependent decrease, with the three top dose groups reaching ~70% decrease at Wk 12 (Figure). None of the five serious AEs were considered drug-related: two events in one pbo pt (hemorrhagic anemia, hemorrhoidal hemorrhage) and three events with BMS-986165 (3 mg QOD: gastroenteritis rotavirus; 3 mg QD: eye injury; 3 mg BID: dizziness). AEs were reported in 51% (pbo), 59% (3 mg QOD), 55% (3 mg QD), 64% (3 mg BID), 80% (6 mg BID) and 77% (12 mg QD) of pts. The most common AEs reported by pts across treatment arms (ranges) included nasopharyngitis (2–16%), headache (4–9%), and diarrhea (2–9%). AEs were generally mild to moderate and resulted in drug discontinuation in 4% of pbo pts and 2–7% of pts across the active doses. There were no significant changes in liver enzymes, blood counts or lipid levels.

Conclusion: In pts with moderate-to-severe PsO, BMS-986165 demonstrated statistically greater efficacy on skin measures vs pbo at doses ≥3 mg QD and a dose-dependent decrease in pain. BMS-986165 was generally well tolerated. Further evaluation in PsO and psoriatic arthritis is warranted. Medical writing assistance provided by Bu Reinen, PhD (Caudex), funded by Bristol-Myers Squibb.

Table 1. Response Rates (%) at Week 12
	Placebo n=45	3 mg QOD n=44	3 mg QD n=44	3 mg BID n=45	6 mg BID n=45	12 mg QD n=44
PASI 75	7	9	39*	69**	67**	75**
PASI 90	2	7	16*	44**	44**	43**
PASI 100	0	2	0	9	18*	25*
sPGA 0/1	7	21	39*	76**	64**	75**
DLQI 0/1	6	18	17	44*	68**	65**
p<0.05 vs placebo *p<0.0001 vs placebo BID=twice daily; DLQI=Dermatology Life Quality Index; PASI=Psoriasis Area and Severity Index; QD=every day; QOD=every other day; sPGA=static Physician Global Assessment

Disclosure: K. A. Papp, AbbVie, Akros, Amgen, Arcutis, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Janssen, Kyowa Hakko Kirin, Leo, 5,AbbVie, Amgen, Astellas, Celgene, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Leo, Merck (MSD), Novartis, Pfizer, Valeant, 8,AbbVie, Akros, Allergan, Amgen, Anacor, Arcutis, AstraZeneca, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GSK, Janssen, Kyowa, Hakko Kirin, Leo, MedImmune, Meiji Seika Pharma,, 2,AbbVie, Akros, Amgen, Baxter, Boehringer Ingelheim, Celgene, Coherus, Eli Lilly, Forward Pharma, Galderma, GSK, Janssen, Kyowa Hakko Kirin, Merck (MSD), Merck Serono, Novartis, Pfizer, Takeda, UCB, Valeant, 9,AbbVie, Akros, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Merck (MSD), Merck Serono, Novartis, Pfizer, Regeneron, Sanofi-Aventis/Genzyme, Valeant, 9,Meiji Seika Pharma, Merck (MSD), Merck Serono, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant, 5,Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant, 2; K. B. Gordon, AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Demira, Eli Lilly, Janssen, Novartis, Pfizer, Sun, UCB, 2, 5; D. Thaçi, AbbVie, Almirall, Amgen, Biogen-Idec, Bio Skin, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chugai, Dermira, Dignity, Eli Lilly, Forward Pharma, GlaxoSmithKline, Leo Pharma, Janssen Cilag, Maruho, MSD, Mitsubishi Pharma, Novartis, Pfizer, 2,AbbVie, Almirall, Biogen-Idec, Bio Skin, Bristol-Myers Squibb, Celgene, Dignity, Galapagos, Leo Pharma, Maruho, Mitsubishi, Novartis, Pfizer, XenoPort, 5,AbbVie, Almirall, Amgen, Biogen-Idec, Bio Skin, Celgene, Dignity, Janssen, Leo Pharma, Pfizer, Roche-Posay, Novartis, Mundipharma, MSD, USB, Sanofi, Sandoz-Hexal, 9,AbbVie, Amgen, Biogen-Idec, Bio Skin, Bristol-Myers Squibb, Celgene, Dignity, Eli Lilly, GSK, Galapagos, Leo Pharma, Janssen Cilag, Morphosis, Novartis, Pfizer, Mundipharma, MSD, Sandoz, Sanofi, UCB, 9,Regeneron, Roche, Sanofi, Sandoz-Hexal, UCB, 2,AbbVie, Almirall, Biogen-Idec, Bio Skin, Bristol-Myers Squibb, Celgene, Dignity, Galapagos, Leo Pharma, Maruho, Mitsubishi, Novartis, Pfizer, XenoPort, 5; A. Morita, AbbVie, Eli Lilly, Janssen, Kyowa Hakko Kirin, Leo Pharma, Maruho, Mitsubishi-Tanabe, Novartis, 2, 5, 8; M. Gooderham, AbbVie, Akros, Amgen, Arcutis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Merck, MedImmune, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, Valeant, 2, 5, 8; P. Foley, Galderma, LEO/Peplin, Janssen, Eli Lilly, 3M/iNova/Valeant, GSK/Stiefel, Abbott/AbbVie, Biogen Idec, Schering-Plough/MSD, Wyeth/Pfizer, Amgen, Novartis, Celgene, Dermira, Boehringer Ingelheim, Cutanea, Celtaxsys, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, 2, 5, 8, 9,Bristol-Myers Squibb, 2, 5, 8, 9; I. G. Girgis, Bristol-Myers Squibb, 1, 3; S. Kundu, Bristol-Myers Squibb, 3; S. Banerjee, Bristol-Myers Squibb, 1, 3.

To cite this abstract in AMA style:

Papp KA, Gordon KB, Thaçi D, Morita A, Gooderham M, Foley P, Girgis IG, Kundu S, Banerjee S. Efficacy and Safety of a Potent and Highly Selective Oral Tyrosine Kinase 2 Inhibitor, BMS-986165, in Patients with Moderate-to-Severe Plaque Psoriasis: A Phase II, Randomized, Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-a-potent-and-highly-selective-oral-tyrosine-kinase-2-inhibitor-bms-986165-in-patients-with-moderate-to-severe-plaque-psoriasis-a-phase-ii-randomized-placebo-controlled-tria/. Accessed .

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