Emerging Therapies in IBD: The Future is Bright October 28 th 2017

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1 Emerging Therapies in IBD: The Future is Bright October 28 th 2017 Nirmal Kaur, MD Director, Inflammatory Bowel Disease Center Division of Gastroenterology Henry Ford Health System

2 Disclosures Research Grants: AbbVie Janssen UCB Roche Genentech Celgene Consulting AbbVie Janssen Takeda AMAG

3 OVERVIEW Current therapeutics Emerging therapies Unanswered questions Future directions

4 IBD Therapy Goals of Therapy: Spare patients from steroids Minimize hospitalizations Minimize need for surgery Minimize risk of therapy

5 Immune Therapy in IBD years of development 2008: Certolizumab 1998: Infliximab 2014: Vedolizumab

6 Biologics: TNF-alpha Antagonists

7 Recently FDA-Approved Vedolizumab Ustekinumab Both novel mechanisms Both FDAapproved within the last 3 years

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9 Vedolizumab: Anti-α4β7-integrin FDA-approved in 2014 Crohn s and UC IV infusion every 8 weeks Extremely safe Expensive Villablanca EJ, et al. Gastroenterology 2011;140:

10 Patients, % Vedolizumab (Anti-Alpha 4 Beta 7 Integrin) For Moderately-to- Severely Active Crohn s Disease: Results at Week 6 in 368 Patients Induction ITT Population P=0.23 P= % of patients showed symptomatic improvement at week 6 Sandborn W. N Engl J Med 2013

11 Patients, % Vedolizumab (Anti- 4 7 Integrin) For Maintenance of Response in Moderately-to-Severely Active Crohn s Disease: Results at Week 52 in 461 Patients Maintenance ITT Population 45% of patients showed symptomatic improvement at week 52 Sandborn W. N Engl J Med 2013

12 Recently FDA-Approved Vedolizumab Ustekinumab Both novel mechanisms Both FDAapproved within the last 3 years

13 QUESTION Which therapy is FDA approved for Crohn s disease? A: infliximab B: adalimumab C: vedolizumab D: ustekinumab E: all of the above

14 QUESTION Which therapy is FDA approved for Crohn s disease? A: infliximab B: adalimumab C: vedolizumab D: ustekinumab E: all of the above

15 Ustekinumab (Stelara): Anti-Interleukin 12/23 Inhibits p40 subunit, which is common to IL- 12 and IL-23 Prevents intracellular pro-inflammatory signaling FDA-approved for plaque psoriasis

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17 Ustekinumab Phase III Data Clinical Response: UNITI-1 vs UNITI 2 Response seen at week 8 or week 6

18 Ustekinumab Phase III Data Study looked at Clinical Remission as an endpoint Statistically significant at week 6 and week 8

19 Immune Therapy in IBD years of development 2008: Certolizumab 1998: Infliximab 2014: Vedolizumab

20 WHAT ELSE CAN WE EXPECT IN LATE ?

21 Research for new therapies in IBD is very active!

22 NOVEL IBD THERAPY FDA Approved Vedolizumab Ustekinumab Phase III Completed: Tofacitinib In Phase III Trials: Etrolizumab In early trials Risankizumab Guselkumab

23 Tofacitinib (Xeljanz): Anti-Janus kinase 3 Inhibits: IL-2, IL-4, IL- 7,IL-9 Inhibits lymphocyte activation and proliferation FDA-approved for RA Phase III studies in psoriasis Sandborn WJ et al. New Engl J Med 2012;367: Vincenti F. Kidney International 2012;82:

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25 Effectiveness of Tofacitinib: Symptom Response 40% of patients demonstrated symptom response at 1 year 8 weeks 52 weeks

26 Effectiveness of Tofacitinib: Intestinal Healing 45% of patients demonstrated intestinal healing at 1 year

27 Dual mechanism of action with two targets Etrolizumab

28 Etrolizumab Currently in Phase III trials for Crohn s and ulcerative colitis

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30 Henry Ford IBD Clinical Trials Etrolizumab for Crohn s and UC: Enrolling now Guselkumab for Crohn s: Coming in 2018

31 However. Despite this explosion in drug development, our current state of clinical research is flawed

32 The State of IBD Research Driven by industry Study endpoints are imperfect Outcomes studies are often single-center, underpowered

33 Current Disease Definition Actual Phenotypes Mild Moderate Severe

34 How do we measure ourselves? Weight loss example Muscle is heavier than fat! Using the right measurement tool is critical Measuring weight may not be ideal

35 Current Therapeutic Endpoints CDAI: Crohn s disease activity index This endpoint only assesses symptoms!!

36 Endpoints are improving

37 Work-Productivity Index Disability in IBD Quality of Life scoring system Depression and Anxiety scoring Fatigue in IBD Most IBD studies do not measure these parameters

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39 Work-Productivity Index Disability in IBD Quality of Life scoring system Depression and Anxiety scoring Fatigue in IBD None of these endpoints met the FDA criteria!

40 QUESTION Which of the following tools is used to assess IBD in clinical studies? A: Symptom scores B: Disability indices C: Work Productivity indices D: Depression scores

41 QUESTION Which of the following is used to assess IBD in clinical studies? A: Symptom scores B: Disability indices C: Work Productivity indices D: Depression scores

42 Route of administration is changing Fewer infusion therapies Self-injections Pills

43 Consortiums are forming

44 CCF Clinical Research Alliance 30 sites nationally expanding to 40 in 2017 NON-PHARMA funded research to answer clinical questions such as: When can biologics be stopped or used intermittently? Which biologic is better than the others? What other therapies are useful besides biologics?

45 National Consortium

46 IBD QORUS Video

47 State of the Collaborative

48 Participating Sites: The Innovators University of Washington Med. Ctr Seattle, WA Dr. Tim Zisman Henry Ford Hospital Detroit, MI Oregon Clinic Portland, OR Dr. Nirmal Kaur and Dr. Jason University Schairer of Chicago Northwestern Chicago, University IL Chicago, IL Dr. Donald Lum and Dr. Harry Bray Midwest Gastroenterology Omaha, NE Dr. Michael Jones University of California San Diego - San Diego, CA Dr. Parambir Dulai, Dr. Siddharth Singh, Dr. William Sandborn Dr. David Rubin Dartmouth-Hitchcock Medical Center - Lebanon, NH Dr. Corey Siegel Penn State Hershey, PA Georgetown University Hospital Washington, DC Dr. Andrew Tinsley & Dr. Emmanuelle Williams Dr. Mark Mattar and Dr. Aline Charabaty St. Anthony Gastro-1 Physicians Memphis, Group Gastroenterology University of North Carolina Chapel Hill, NC TN Oklahoma City, OK Dr. Tauseef Ali Dr. Millie Long Cedars-Sinai Medical Center Los Angeles, CA Dr. Ziad Younes Dr. Gil Melmed University of Southern California Los Angeles, CA Dr. Caroline Hwang Saratoga-Schenectady Gastroenterology Associates - Saratoga, NY Dr. Arthur Ostrov Dr. Leonard Baidoo Baylor Houston, Texas Dr. Jason Hou Gastroenterology Winthrop Gastroenterology Associates Providence, Mineola, NY RI Dr. Dr. Samir Raluca Shah Vrabie Shreveport Gastrointestinal Specialists Shreveport, LA Dr. Humberto Aguilar

49 IBD Plexus Landscape Pediatric RISK Study Adult Prospective SPARC Internet-based CCFA-PARTNERS QORUS Real World Evidence Registry Study Programs Components Adult & Pediatric Registries Biobank & LIMS Data & Analytic Platforms Centralized Analytical Lab High Performance Computing Researcher Portal Study Programs Components

50 IBD QORUS What will this lead to? Large scale research with tens of thousands of patients Population-based data on disease phenotype that is currently excluded from industrysponsored trials Improved population health management strategies

51 THE FUTURE IS BRIGHT

52 THANK YOU!