April Guro Løvik Goll, MD PhD. Prosjektkoordinator revmatologi, Nor-Switch

Transcription

1 April 2016 Guro Løvik Goll, MD PhD Prosjektkoordinator revmatologi, Nor-Switch

2 LIS TNF/BIOrecommendations LIS TNF/BIO spesialistgruppe januar 2015

3 LIS 2015 Hospira offered 51% discount for Inflectra, but Orion Pharma offered 72% discount compared with the listed price for originator Infliximab, Remicade from MSD. This meant hospitals could treat one patient on Remsima for three years at the same cost as one patient for one year with Remicade.

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5 Uptake of biosimilar infliximab in the Nordics 69% 89,9% INX CT-P13 INX CT-P13 38,2% 6,5% INX CT-P13 CT-P13 Dagens Medisin, 16/2015 Thursday 24 th September, page 12-13

6 Interchangability is a key question in Norway (and other parts of the world) Is switching from from originator to biosimilar infliximab safe? (efficacy, safety, immunogenicity) Can patients on treatment with INX be switched to CT-P13 to reduce medication cost (and improve access to bdmards for more patients in areas with major financial restrictions)?

7 Statsbudsjettet 2014: Det foreslås 20 mill. kroner til kliniske studier Det foreslås 20 mill. kroner til kliniske studier av bytte mellom biologiske og biotilsvarende legemidler Når et biologisk legemiddel går av patent åpnes det for at andre produsenter kan lage tilvarende biologiske legemidler Det er som oftest ikke mulig å lage helt identiske kopier av biologiske legemidler slik tilfellet er med syntetiske legemidler (generika), herav navnet biotilsvarende Når europeiske legemiddelmyndigheter godkjenner et biotilsvarende legemiddel, er det en bekreftelse på at det har samme virkning som originallegemidlet Ev. bytte mellom det originale biologiske legemidlet og det biotilsvarende legemidlet hos pasienter som allerede får behandling, er ikke en del av godkjenningen

8 The Nor-Switch study A randomized, double-blind, parallel-group study to evaluate the safety and efficacy of switching from innovator infliximab to biosimilar infliximab compared with maintained treatment with innovator infliximab in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn s disease and chronic plaque psoriasis

9 Organisation Coordinating center Dept of Rheumatology, Diakonhjemmet Hospital (on behalf of the South-East Health region authority) Multidisciplinary and multiregional project group with special competence in statistics (power calculations), immunogenicity, health economic evaluations, performance of strategy trials Representation from NorCRIN Representation from the three relevant patient organisations a team of three coordinators from dermatology, gastroenterology and rheumatology (50% positions) Monitoring by the regional health authorities All funding is from the Norwegian government

10 National multicenter study n=40 16 Rheuma R G Tromsø 19 Gastro 5 Derma R R G Mo I Rana Bodø R Levanger Kongsvinger R R G Ålesund St. Olav R G H Lillehammer R G Gjøvik Hamar G Elverum G G H R Førde R G H R H Bergen Haugesund Østfold R G Bærum G Diakonhjemmet R G Rikshospitalet G H Ullevål G Ahus G Martina Hansen R R G Kristiansand Tønsberg G G Arendal Skien R G

11 The Nor-Switch study Remicade Remicade Stable treatment >24 w Baseline n = 250 n = 250 Remsima 52 w Primary endpoint: disease worsening Secondary endpoint: safety, immunogenicity Randomization A national, randomized, double-blind, parallel-group study Evaluate the efficacy and safety of switching from innovator infliximab (Remicade) to biosimilar infliximab (Remsima) Ulcerative colitis, Crohn s disease, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, psoriasis

12 The Nor-Switch study Remicade Remicade Stable treatment >24 w Baseline n = 250 n = 250 Remsima 52 w Primary endpoint: disease worsening Secondary endpoint: safety, immunogenicity Randomization October 2014: first patient enrolled in Nor-Switch June 2015: last patient enrolled in Nor-Switch

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14 Disease worsening RA and PsA Increase in DAS 28 of 1.2 from randomization, a minimum DAS 28 score of 3.2. SpA Increase in ASDAS of 1.1 from randomization and a minimum ASDAS of 2.1 Ulcerative colitis Increase in partial Mayo score of 3 points from randomization and a minimum partial Mayo score of 5 points. Crohn s disease Increase in HBI of 4 points from randomization and a minimum HBI score of 7 points. Psoriasis Increase in PASI of 3 points from randomization and a minimum PASI score of 5. Patient and investigator consensus on disease worsening If a patient does not fulfill the formal definition, but experiences a clinically significant worsening according to both the investigator and patient and which leads to a major change in treatment.

15 Randomized patients in total Gastro 199 Rheuma Oct Nov Dec Jan Feb March April May June 35 Derma

16 Diagnosis distribution Psoriasis 35 Rheumatoid arthritis 78 Crohn's disease 155 Spondyloarthritis 91 Ulcerative colitis 93 Psoriatic arthritis 30

17 Status: The Nor-Switch study n=364 Remicade Remicade Remsima Stable treatment >24 w Remsima Baseline 52 w 76 w Randomization Intervention period Follow-up period

18 NOR-SWITCH extension study Guro Løvik Goll

19 What happens after 1 year in NOR-SWITCH?

20 Switching outside of Nor Switch After the 2015 LIS-meeting, many departments switched their patients from Remicade til Remsima i.e. prior to NOR-SWITCH study results. Follow-up of switched patients is important effect, safety, immunogenicity Set of core data, offered by the NOR-SWITCH study group, registering key data at Time of switch Time of every infusion for a full year after switching If stopping Remsima Local quality studies recommended

21 6 month open extension of NOR-SWITCH «Forlengelsesstudien» «Ekstensjonsstudien»

22 NOR- SWITCH Study design Exploring switching for non-medical reasons Primary endpoint: Effectiveness (disease worsening) Primary endpoint Week 52 Switch Screening Stable patients (at least 6 months) Randomisation 1:1 N= 500 INX CT-P13 Disease worsening W52 Disease worsening W52 Follow-up W78 Follow-up W78 A randomized, double-blind, parallel-group study to evaluate the safety and efficacy of switching from innovator infliximab to biosimilar infliximab compared with continued treatment with innovator infliximab in patients with rheumatoid arthritis, spondylarthritis, psoriatic arthritis, ulcerative colitis, Crohn s disease and Chronic plaque psoriasis Assumption : 30% worsening in 52 weeks Non-inferiority margin:15% Open Label Follow-up

23 Status: The Nor-Switch study n=364 n=>300 Remicade Remicade Remsima Stable treatment >24 w Remsima Baseline 52 w 76 w Randomization Intervention period Follow-up period

24 Why do an extension study? More switch-data are needed Good patient care Longer time of observation Open vs blind switch to Remsima Much simpler logistics than in main study Continue valuable national collarboration

25 Dissemination of study results April 2016

26 Status «Go» from the health regions 20th March 2014 Protocol sent EC and regulatory agency May 2014 Revised July 2014 Approved 11th August 2014 National initiation meeting 10th September 2014 First patient in: 24th October Inclusion stopped 15 June 498 patients included Last infusion will be 15th June 2016 Results: Late summer/early fall 2016 Amendment: Open-label follow-up for 26 weeks all patients on CT-P13. Extension completed December 2016.

27 Publication/congress abstracts Main article submission fall of 2016 UEGW October 2016 ACR November 2016

28 Conclusions Safety, efficacy and immunogenicity related to switching from INX to CT-P13 is being explored in a government supported study in Norway designed as a non-inferiority RCT (NOR-SWITCH). Study is on track An open-label 6-month follow-up of NOR-SWITCH is ongoing 364 pts have completed main study so far, more than 300 included in 6 month follow-up Results from NOR-SWITCH expected fall of 2016

29 APRIL 2016 Thank you

30 Superiority design 0 = ingen forskjell mellom gruppene Konfidensintervallet inneholder ikke null 95% sikkert at det er en forskjell mellom gruppene

31 Non-Inferiority Non-inferiority ikke vist : konfidensintervallet krysser non-inferiority marginen

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33 Design RCT 1:1 stratification (disease) Blinding procedures Primary endpoint Disease worsening based on worsening in composite scores or Consensus between patients and physician on disease worsening Disease specific secondary endpoints Cost-effectiveness analysis Follow-up 12 months Biobank

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35 Serious Adverse Events Type of SAE No Infections 11 Neoplasia 5 Elective surgery 6 Trauma 4 Cardiology 3 Other 7

36 Study discontinuation Reason for discontinuation No Included, not randomized 10 Withrawal of informed consent 6 Adverse event 6 Investigators decision 5 Violation of eligibility 1 Lost to follow-up 1 Other 4 TOTAL 33