The Future Role of Biosimilars: An Unknown Frontier in IBD Treatment Miguel Regueiro, MD, FACG Professor of Medicine Medical Director, IBD Center Senior Medical Lead, Specialty Homes University of Pittsburgh Medical Center Why even have this talk? Why not stick with what we know and love! 2 Copyright American College of Gastroenterology 1
One approach to healthcare costs is similar to this car 4 Copyright American College of Gastroenterology 2
Maybe we can get away with... 5 Biosimilars Biosimilars are a similar copy of an originator biologic therapy. The originator is also sometimes called the reference product or innovator. What should be the same? Strength Route of administration Effectiveness Safety profile What is different? They are NOT an identical copy in every way (glycosylation may differ) Copyright American College of Gastroenterology 3
Thousands of participants for disease indications such as: Rheumatoid arthritis, Crohn s, ulcerative colitis Originator Biologics Biologic developed and tested FDA Application Clinical Trials Biosimilars Biologic developed and tested FDA Application Clinical Trials Clinical trials on one or more disease indication(s) from originator Example: Rheumatoid arthritis Must demonstrate safety and effectiveness FDA and Drug Sponsor Review Meeting Biologic License Application FDA and Drug Sponsor Review Meeting Biosimilar Biologics License Application Must demonstrate high similarity to reference drug. No clinically meaningful differences Example: Approval for IBD, RA, AS Drug Approval and Labeling Drug Approval and Labeling Example: Approval for IBD, RA, AS Biosimilars Can be Extrapolated to Other Indications Comparison studies of a biosimilar that show equivalent efficacy and safety to the originator in ONE INDICATION may be EXTRAPOLATED to all indications for the originator EXAMPLE: biosimilar infliximab that works equally well in rheumatoid arthritis can be extrapolated and receive FDA approval without any additional studies for Crohn s disease, ulcerative colitis, ankylosing spondylitis, psoriasis and psoriatic arthritis. Indication 6 Indication 6 Adapted from: US Biologics Price Competition and Innovation Act of 2009 Indication 1 Indication Indication 4 Indication 2 Indication 3 Mechanism of action Pharmacokinetics Immunogenicity Toxicities Copyright American College of Gastroenterology 4
Interchangeable Biosimilars Interchangeable designation of biosimilars may allow for free exchange with originator biologics with no greater risk of adverse effects or diminished efficacy Could allow pharmacy substitution without prescriber intervention Subject to each state s laws and regulations governing drug FDA determines whether a biosimilar is interchangeable or not Requires studies of switching between originator and biosimilar Adapted from: US Biologics Price Competition and Innovation Act of 2009 Biosimilars in Development Over 650 biosimilars in development 1 Nearly 50% of biosimilars are in pre clinical trial stage 1 It takes 7 to 8 years to develop a biosimilar, at a cost of between $100 million and $250 million 2 1 Radar RA. Bioproc Int. 2013; 11(6): S16 23. 2 Blackstone EA, et al. Am Health Drug Benefits. 2013;6(8):469 478. Copyright American College of Gastroenterology 5
Biosimilar for IBD Inflectra TM is the first FDA approved biosimilar for inflammatory bowel disease Has biosimilarity to infliximab (Remicade ) Not interchangeable Studied in: Ankylosing Spondilitis Rheumatoid Arthritis Extrapolated to: Crohn s disease (in adults and children) Ulcerative colitis (in adults) Not available yet, projected 2018 Source: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm494227.htm accessed May, 2016 Issues with Biosimilars Risk of having the originator therapy in patient SWITCHED to the biosimilar in stable patient unknown Confusion regarding names and branding like: Potential for immunogenicity or cross reactivity unknown Means that anti drug antibodies will cross react Loss of response or allergic reaction to the originator will occur equally with the biosimilar Remicade Originator VS Remsima Biosimilar In Europe Copyright American College of Gastroenterology 6
HOW HAVE BIOSIMILARS PERFORMED IN IBD? IFX Biosimilar (CT P13): Efficacy Results from a National Observation Cohort Prospective, nationwide, multicenter observational cohort to assess efficacy and safety of CT P13 in CD and UC Follow up 108 weeks for CD and 54 weeks for UC Clinical disease activity assessed at each visit Biomarkers assessed every 3 months Sera for trough and antidrug antibodies obtained at baseline, 3, 6, and 12 months Imaging/endoscopy completed every 12 months Gecse K. ECCO 2015 Copyright American College of Gastroenterology 7
Results of IFX Biosimilar (CT P13) Significant decrease in CDAI at 2 and 6 weeks compared to baseline (p<0.001) Decrease in CRP from 23.5 mg/dl at baseline to 11.3 and 15.4 at Week 2 and 6, respectively Decrease in pmayo from 6.4 at baseline to 3.7 and 3.6 at Week 2 and 6, respectively 4 allergic reactions occurred all in patients with prior anti TNF exposure Gecse K. ECCO 2015 Efficacy and Safety of IFX Biosimilar (CT P13) in Korea Retrospective multicenter study of IFX biosimilar (CT P13) (n=106) CD (n=55) 58% IFX exposed 42% anti TNF naïve UC (n=51) 20% IFX exposed 80% anti TNF naive Limitations: No comparator studies, therefore no firm biosimilarity conclusions can be drawn. Key questions remain on switch cohort, statistical methods used and missing data, such as unknowns about whether responder analysis, LOCF, etc. that might explain such high responses Yoon Suk J, et al. ECCO 2015 Copyright American College of Gastroenterology 8
Efficacy of CT P13 in Anti TNF Naïve Patients at 8 Weeks Limitations: No comparator studies, therefore no firm biosimilarity conclusions can be drawn. Key questions remain on switch cohort, statistical methods used and missing data, such as unknowns about whether responder analysis, LOCF, etc. that might explain such high responses Yoon Suk J, et al. ECCO 2015 Current Studies of Biosimilars in IBD Study Population Study CRP Gecse et al. Hungary (2015) DDW Sympo Norway (2015) Jarzebicka et al. Poland (2015) Suk et al. Korea (2015) Murphy et al. Ireland (2015) CD=90 UC=51 CD=46 UC=32 CD=32 Pediatrics CD=55 UC=51 IBD=36 Infliximab biosimilar induction Biosimilar induction Switch IFX to biosimilar CT P13 Remsima switch from IFX or ADA or anti TNF naive Descriptive Inflectra=14 IFX=22 Decreased 23.5 to W2: 11.3 and W6: 15.3) Decreased Decreased (5.1 to 0.6) not reported Inflectra Increased (93%) Other Outcomes Allergic reactions 6/141 Remission CD=76% UC=56% Safe switch to biosimilar Maintenance of Remission CD=86% UC=67% Inflectra Increased surgery (29%) and readmission (80%) Copyright American College of Gastroenterology 9
Anti TNFs account for 20 25% of Total Costs from Biologics States with Laws about Biosimilars www.ncsl.org, accessed Dec 9, 2015 Copyright American College of Gastroenterology 10
The Reality: Biosimilars are here Canada 4 INNs are used, when they exist. Awaiting WHO final decision. USA 1 2 FDA has not provided guidance. Recent decisions used pre fix. (tbo filgrastim, zivaflibercept) EC/EMA 3 Does not support distinguishable INNs. EMA encourages prescribing by brand name. Japan 6 Biological qualifier recommended Brazil 7 Biosimilar guidance does not address naming. Australia 5 Distinguishable nonproprietary name process implemented then halted pending WHO guidance (1) CDER Zaltrap application summary: Accessed August 1, 2013. (2) FDA Week (vol. 18, No 36, September 7, 2012) (3) Eu Comm. Pharmaceutical Committee Meeting. 23 Oct, 2013 (4) Health Canada Drug Products Database: Terminology (5) Australian TGA 17 July, 2013. Evaluation of Biosimilars (6) WHO 57 th Consultation on INNs Geneva Switzerland 2013 RDC 55/2010 Pharmacovigilance, Tracking and Traceability Company Confidential 2014 The other reality: THIS is what the Health Plans see when they see Inflammatory Bowel Disease Top 10 costs for IBD pts - #1 and 2 mostly biologic, #3 ER/Hospital if we could cut biologic cost in half.. What Types of Service do these Members Utilize? Rank Financial Service Type Total PMPM % of Total Claim Expenditure Unique Members Units/ 1,000 with at least 1 Claim % of Members in population with at 1 least 1 claim 1 Pharmacy $616.13 31.6% 32,591 2,190 92.2% 2 Injectable Drugs $370.18 19.5% 4,549 1,126 47.4% 3 IP Medical Surgical $306.48 16.2% 408 523 22.0% 4 Specialist $130.21 6.9% 10,553 2,226 93.7% 5 Outpatient Surgery $71.08 3.8% 924 1,238 52.1% 6 Emergency Room $67.94 3.6% 1,389 1,119 47.1% 7 Lab Services $58.84 3.1% 5,785 2,197 92.5% 8 PCP $40.26 2.1% 5,577 2,013 84.7% 9 Observations $35.04 1.8% 200 292 12.3% 10 High Tech Radiology $34.25 1.8% 478 975 41.0% 29 Copyright American College of Gastroenterology 11
Building the IBD Home of Tomorrow A New Model for 360 o Subspecialty Patient Centered Care Miguel Regueiro, M.D. Professor of Medicine Western PA IBD Medical Home Population Copyright American College of Gastroenterology 12
Cost of First 100 pts: based on UPMC HP claims data from the one year prior to enrollment in the IBD medical home Total $3,685,064 Med Cost $1,348,142 PMPM $2,910 33 Proposed Three (3) Year Plan UPMC Health Plan will support the staffing for the program; adjusting based on membership Target is 350 members enrolled for the first year (900 by year 3). Expected savings anticipated from: decreased unplanned care clinical pathways to decrease variation in care biologic utilization (home infusions, biosimilars) Copyright American College of Gastroenterology 13
Theoretical Scenarios coming soon? The Health Plan will only approve biosimilar antitnf for your patient the biosimilar is 30% lower cost 34 yo female with severe UC in remission x 2 yrs with antitnf/aza HP: switch your patient to the biosimilar 27 yo newly dx d CD pt with perianal fistula and deep ulcers in colon/ileum HP: start your patient on the biosimilar 35 Infliximab Biosimilar is Effective and Safe When Switching from Branded Infliximab Percent of Patients Methods: Multicenter study of consecutive patients on CT P13 (infliximab (IFX) biosimilar) N=547 patients (IFX naïve, previous anti TNF exposure, and switched from IFX) Results: 311 anti TNF naïve, 139 previous anti TNF exposure (IFX=31, ADA=105, GOL=3) 97 switched from IFX to CTP 13 100 80 60 40 20 0 Preliminary efficacy estimates* Naïve Previously exposed Switch 93 99 91 88 88 Clinical remission at week 12 GOL, golimumab; IRR, infusion reaction rate; NS, not significant Fiorino G, et al. Presented at DDW. May 2016. Abstract 439. 93 Clinical remission at week 24 Infusion reactions (typically after a drug holiday) Naive vs previously exposed Infusion reactions p value Incidence IRR: 0.21 (0.09 0.47) <0.01 3% Naïve vs switch IRR: 0.70 (0.24 2.15) NS 7% Previously exposed vs switch Other AEs Naive vs previously exposed IRR: 3.25 (1.33 9.06) <0.01 15% Other AEs p value Incidence IRR: 0.54 (0.21 1.39) NS 3% Naïve vs switch IRR: 1.46 (0.44 6.21) NS 4% Previously exposed vs switch IRR: 2.71 (0.78 11.8) NS 7% Copyright American College of Gastroenterology 14
Biosimilars will be a reality very soon Copyright American College of Gastroenterology 15