This document discusses several points related to the affordability and reimbursement of treatments for rare bleeding disorders: 1) It describes different reimbursement strategies from least to most restrictive, including risk sharing arrangements and technology leasing where payment is based on outcomes rather than just products delivered. 2) It provides examples of risk sharing funding models used for Trastuzumab and how net health benefits were positive after shorter time periods under a technology leasing model. 3) It discusses the experience with the gene therapy Glybera, including uniQure deciding not to renew its marketing authorization due to limited usage and high monitoring costs required by regulators. 4) It reviews health technology assessments of Glybera in France

1. Affordability of haemophilia treatments
Points for discussion
Albert Farrugia
Adjunct Professor, School of Surgery, University of Western Australia
Senior Scientific and Regulatory Advisor, Kedrion S.p.A
The 10th WFH Global Forum on Research and Treatment Products for Bleeding Disorders
Montreal – November 8 - 10, 2017

2. S e l e c t e d r e i m b u r s e m e n t s t r a t e g i e s o r d e r e d a c c o r d i n g t o r e s t r i c t i v e n e s s
2
Value in Health Volume 17, Issue 4, June 2014, Pages 438-444

3. Risk Sharing Arrangem ent s
Technology Leasing Reimbursem ent Strateg y
• Payment mechanisms in which the suppliers receive payment only for
delivered outputs rather than delivered products.
• Allows payers to take into account uncertainties in therapeutic outcomes.
• Reimburse for healthy time rather than product/technology

4. Net Health Benefit Probabil ity Map
funding for Trastuzim ab
4
V A LUE IN HEALTH 17 (2014) 438 – 4 4 4
Standard Reimbursement Strategy
• Net Health Benefit is +ve after 19.5 years
• 90% credible range at 50 years = -0.55 to
+0.76 QALYs
Technology Leasing Reimbursement Strategy
• Net Health Benefit is +ve after 6.5 years
• 90% credible range at 50 years = -0.39 to
+0.56 QALYs

5. • uniQure not renew its marketing authorization for Glybera in Europe, which has now expired.
• Glybera was first approved in October 2012 for hereditary lipoprotein lipase deficiency (LPLD) – 1 in a million.
• Glybera provided a one-off solution with efficacy for at least six years.
• uniQure: “Glybera’s usage has been extremely limited, and we do not envision patient demand increasing materially in the
years ahead.”
• Approval came with hefty maintenance costs:
 Required by the European Commission to monitor patients over a long period of time, conduct a
Phase IV clinical trial, undergo annual regulatory inspections and increase risk management
precautions.
• uniQure will focus on Huntington’s disease, hemophilia B, and congestive heart failure.
• Glybera will still be available to patients approved for the treatment before the withdrawal date.
• The post-authorization Phase IV study will be terminated.
https://labiotech.eu/uniqure-glybera-marketing-withdrawn/

6. French HTA (Haute Authorité de Santé)
• “A moderate effect on triglycerides and on
episodes of pancreatitis has been observed
but this effect was not sustained in the
medium- and long-term” (in line with
submitted efficacy data showing only
transient efficacy);
• “The clinical relevance of the chosen
primary efficacy endpoint (reduction in the
triglyceride level) is debatable”;
• “Uncertainties about the short- and
medium-term safety of this gene therapy,
which cannot be re-administered because
of its action mechanism, remain.”
Glybera – Health Technol o gy Assess m e nt s
• Germany HTA (G-BA)
• Glybera initially positioned as a
community product (does not require
hospital admission for
administration).
• Hence evaluated through AMNOG
and granted “unquantifiable
additional benefit”.
• G-BA concluded that clinical data did
not support an additional
benefit
͢ “unquantifiable”.
• Changed to a hospital-only product,
• allowing direct price negotiations
between hospitals and payers.
• Direct hospital/payer negotiations
used for the single patient treated in
Berlin in September 2015. €900,000
following an agreement with DAK.
• No other insurances followed DAK

7. G-BA extent of additional benefit for orphan and non -
orphan drugs inthe period 2011 – 2 0 1 5
7
Result of ODD at MA
stage : NB tension
between MA and HTA
Expert Opinion on Orphan Drugs, 4:5, 453-455

8. Paying for «New Therapi es »f or haem ophili a –
evolvi ng perspecti v es
• Satisfactory (?) alternative therapies exist.
• Endpoints are unequivocal.
o Target ABR?
• Uncertainity exists
o Effectiveness vs efficacy
o Emicizumab + tolerisation?
o Gene therapy – how frequent?
• Risk sharing models?