PSORIASIS DRUGS IN EUROPE - MARKET ACCESS DECISIONS IN COMPARISION BASED ON THE PRISMACCESS DATABASE

PSORIASIS DRUGS IN EUROPE - MARKET ACCESS DECISIONS IN COMPARISION BASED ON THE PRISMACCESS DATABASE Lutz Vollmer 1,3, Daniel Dröschel 1,4, Bruno de Paz 2, Stefan Walzer 1,5 1 MArS Market Access & Pricing Strategy GmbH, Weil am Rhein, Germany 2 Prioritis SA, Paris, France 3 University of Applied Sciences Rottenburg / Neckar, Rottenburg, Germany 4 SRH Mobile University Riedlingen, Germany 5 State University Baden-Württemberg Lörrach, Germany ISPOR EUROPE Glasgow, November 2017

Psoriasis Long-lasting autoimmune disease characterized by raised, red, scaly patches of abnormal skin. Typically affects the outside of the elbows, knees or scalp, though it can appear on any location. A non-curable disease; however, treatment options help to control the disease for many patients. Psoriasis can be mild, moderate or severe. Severity is based on how much of the body is affected by psoriasis. However, the severity of psoriasis is also measured by how psoriasis affects a person's quality of life. This study provides information on the current reimbursement situation with biological agents in various European countries, which are part of the treatment plans of moderate to severe Psoriasis.

Methods The international HTA database Prismaccess includes over 20.000 worldwide decisions by market access authorities. This study includes the decisions of : France Transparency Committee Haute Autorité de Santé TC HAS / CEESP England National Institute for Health and Care Excellence - NICE Scotland Scottish Medicines Consortium - SMC Germany Federal Joint Committee - G-BA, IQWIG Sweden The Dental and Pharmaceutical Benefits Agency, TLV As therapeutic area Psoriasis was chosen. Investigation period was from 2011 to October 2017. For comparison, the decision scale was transformed in to a traffic light system.

Added benefit in comparison France TC HAS - ASMR Germany G-BA - Added benefit Sweden TLV - Cost-Effect. England NICE - Cost-Effect. Scotland SMC - Cost-Effect. Recommended without limitations ASMR IV and higher in all subgroups Added benefit in all subgroups Recommended Accepted Accepted Recommended with limitations ASMR V / Insufficient in at least one subgroup No added benefit in at least one subgroup Recommended with restriction / and condition Accepted (with limitations) Restricted Not recommended / not reimbursed Insufficient Lesser benefit Not recommended Not recommended Not recommended

Overall development 66 decisions 27 drugs 15 active ingredients Total 66 24 / 1 TC / CEESP 7 / 4 IQWIG / G-BA 14 6 10

Drug therapies Established Therapies Adalimumab - HUMIRA Betamethasone Brodalumab Calcipotriol Calcipotriol / Betamethasone Clobetasol Etanercept - ENBREL Fumaric acid esters Infliximab - REMICADE Methotrexate Mometasone Ustekinumab - STELARA New upcoming therapies / Biologics Apremilast - OTEZLA Dimethyl Fumarate - SKILARENCE Brodalumab - KYNTHEUM Ixekizumab - TALTZ Secukinumab - COSENTYX

France Overall: 24 decisions with an SMR of Substantial in 23 subpopulations Moderate in 2 subpopulations Insufficient in 10 subpopulations And mostly no improvement in the added benefit

France Focus on new therapies (4 decisions) Decision for an insufficient benefit increased. Also added benefit for an ASMR of IV increased.

Sweden 14 decisions incl. re evaluations Majority is approved and no negative recommendation New therapies (Apremilast, Brodalumab, Ixekizumab, Secukinumab) all approved with restriction (and condition)

Scotland Total 10 decisions with the majority restricted. Not recommended due to nonsubmission. New therapies: only Apremilast was considered as cost-effective and accepted without limitations.

England Overall 6 decisions Mainly accepted with limitations New therapies are all accepted with limitation Apremilast first submission not recom-mended because not costeffective

Germany Only new therapies were rated in the benefit assessment, with the majority of an added benefit.

Date of decision 02/12/2015 Moderate V 15/06/2015 Approved with restriction and condition 25/11/2015 23/11/2016 Apremilast - OTEZLA Results ACT Patient population Clinical Data Not recommended Accepted with limtations Adalimumab/ Etanercept/Infliximab /Secukinumab/ Ustekinumab e.g. Methotrexate or biologic treatment BSC (Moderate) Biologics (Severe) 08/06/2015 Accepted Etanercept/Infliximab /Adalimumab/ Ustekinumab Moderate and severe who not responded... to other syst. therapies à 2 nd line, not 3 rd line Moderate and severe who not responded... to other syst. therapies Only severe disease (not Cost-Effective for moderate) Moderate and severe who not responded... to other syst. therapies Against Placebo -> moderate SMR! Against Placebo was accepted Against Placebo and NMA was accepted Against Placebo and NMA was accepted 06/08/2015 No added benefit proven Adalimumab/ Infliximab/ Ustekinumab Moderate and severe who not responded... to other syst. therapies Against Placebo was not accepted for benefit assessment

Date of decision 16/09/2015 05/10/2016 21/05/2015 19/05/2016 Secukinumab - COSENTYX Results ACT Patient population Clinical data Substantial IV (Insufficient for other) Approved with restriction and condition Adalimumab/Apremilast/ Ciclosp./Etanercept/Inflix imab/ixekizumab/ Methotrexate/Ustekinum ab Etanercept/Adalimumab/ Infliximab/Ustekinumab Only severe chronic forms (3rd line treatment) and further failure of at least two treatments Moderate to severe who do not respond to systemic FIXTURE/ERA SURE/FEATUR E/JUNCTURE/ CLEAR + NMA FIXT./ERAS./ FEAT./JUNC./ CLEAR+NMA 22/07/2015 Accepted with limitations Biological treatments 08/06/2015 Restricted Etanercept/Infliximab/ Adalimumab/ Ustekinumab 27/11/2015 15/08/2017 A Considerable (after resub.) B Considerable C Minor A)Fumaric acid esters/ cyclosporine/methotrexa te/phototherapy BC)/Adalimumab/ Infliximab/Ustekinumab Severe AND when failed to respond to standard systemic therapies When failed to respond to standard systemic therapies A) Moderate to severe plaque psoriasis who are eligible for systemic therapy BC) not responded adequ. FIXT./ERAS./ FEAT./JUNC./ + NMA FIXTURE,ERAS URE,FEATURE, JUNCTURE A) PRIME B)CAIN457A2 223/ERAS./FI XT/FEAT./JUN CT. + NMA

Date of decision 05/10/2016 Substantial V (Insufficient for other) 30/09/2016 Approved with restriction 26/04/2017 Accepted with limitations Ixekizumab - TALTZ Results ACT Patient Population Clincal data Secikinumab (the most) Adalim./Aprem./Ciclosp./ Etaner./Inflixi./Ixekizu./M ethotr./ Ustekinu./ Secikinumab (Indirect comparison) Other biological treatments 10/04/2017 Restricted Etanercept/Infliximab/ Adalimumab/Ustekinuma b 15/08/2017 A Considerable B Minor A) Fumaric acid esters/ /cyclosporine/methotrex ate/ phototherapy B) Adalimumab/ Infliximab/Ustekinumab Only severe chronic forms (3rd line treatment) and further failure of at least two treatments Moderate to severe who do not respond to systemic Severe AND when failed to respond to standard systemic therapies Moderate to severe who do not respond to systemic A) Moderate to severe who are eligible for systemic therapy B) Moderate to severe who do not responded adequate. UNCOVER 1,2,3 RHBS + Ind. comp. UNCOVER 1,2,3 + Indirect com. UNCOVER 1,2,3 + NMA UNCOVER 1,2,3 + NMA RHBZ RHBS

Date of decision Brodalumab - KYNTHEUM Results ACT Patient Population No information available yet 31/10/2017 Approved with restriction In development Ixekizumab and Secukinumab (indirect comparison) Only subsidized for patients who have been treated with TNF inhibitors or where this is not appropriate. Because not shown reasonable cost in relation to TNF inhibitor In development In development

Date of decision Dimethylfumarate - SKILARENCE Results ACT Patient Population No information available yet No information available yet 06/09/2017 Approved with limitations In development Placebo Fumaric acid esters severe and patients who failed to other systemic therapies Cost effective for severe subpopulation In development

Summary The MA label for moderate and severe patients for new biologic therapies is not fully implemented by all authorities. Range from full access (Germany) to 3 rd line treatment (France) The appropriate comparator therapy is different specified by each authority. In general clinical data was mostly accepted. Clinical data based on Placebo e.g. is assessed differently by each authority. Treatments are seen mostly as cost-effective to patients with severe psoriasis, and are a reason for restrictions.

Implications A one size fits all HTA is not recommendable for Europe given the significant differences in the application of HTA methods and preferences for analyses. Especially patients with moderate Psoriasis might suffer from different country-specific access to new treatments.

Further Information Further information on the reimbursement status is available in the Prioritis Analysis Report Psoriasis Stop by at Stand 602, Hall 4 to drop your E-Mail for a free version

HTA decisions Including regional decions from Italy and Spain

Timelines MA to HTA and Reimbursement