Regenerative medicine: A European HTA perspective, Towse at ISPOR Nov 2014

1. Adrian Towse
ISPOR 2014 / Issues Panel
Amsterdam • 11th November 2014
Regenerative Medicine: A European HTA perspective

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Agenda
•Regenerative medicine: definition and value
•Regenerative medicine in Europe
•Treatments with EMA authorisation
•Their reimbursement status in Europe
•Other regenerative treatments
•HTA and Budget Challenges
•Ways forward

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Regenerative Medicine: Definition
•‘Regenerative medicine replaces or regenerates human cells, tissue or organs, to restore or establish normal function.’1 Includes different types of therapies. For instance2:
•Stem cell therapy
•Cellular therapy
•Tissue engineering
•Gene therapy (sits between stem cell and cellular therapy)
•Regenerative medicine has the potential to “deliver new, innovative therapies, or even cures, where conventional approaches do not provide adequate solutions3 1Mason, C., & Dunnill, P. (2008) 2What is regenerative medicine? McEwen Centre for Regenerative Medicine. 3Science and Technology Committee (2013) Regenerative medicine report. House of Lords. London

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Treatments with EMA authorisation
•Glybera (2012): Gene therapy to treat lipoprotein lipase deficiency.
•Chondrocelect (2009) and MACI (2013): Tissue-engineered products to treat cartilage defects in knees.
•Provenge (2013): Cell therapy to treat prostate cancer.

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Reimbursement status in Europe
•Glybera: launch delayed to add data (expected in the fourth quarter of 2014/first quarter of 2015) 1.
•Chondrocelect and MACI: in scoping stage in NICE. Additionally, Chondrocelect is currently available for patients and reimbursed in Belgium, the Netherlands and Spain2. HAS, in France, has published a negative opinion of Chondrocelect due to paucity of clinical evidence.3
•Provenge: company plans to make it available in Europe (announced in March 2014), starting with UK and Germany. NICE and IQWiG have not yet expressed an opinion on this product.4 Sources: 1The Pharmaletter (2014). 2Reuters (2014). 3HAS (2010). 4Dendreon (2014).

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Other regenerative treatments
Not EMA regulated, treated as surgical interventions
•Bone marrow transplantation: often used to treat conditions which damage bone marrow, such as leukaemia, so that it is no longer able to produce normal blood cells.
•Replacement skin cells, grown by a process called tissue culture, can be used to help burn wounds heal.
•Pancreatic islet transplantation: islet cells make and release insulin. After this procedure diabetic patients can become insulin- independent.
•NICE has issued an interventional procedures guidance [IPG274] about autologous pancreatic islet cell transplantation for improved glycaemic control after pancreatectomy. These are typically reviewed at a provider level with some payer input Source: Science and Technology Committee (2013) Regenerative medicine report. House of Lords. London

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HTA and Budget Challenges
•“Cures” are, in effect, disease modifying therapies for chronic diseases with all of the associated problems
•Short term trials using surrogate markers may not produce relevant clinical outcomes
•Outcomes may not be sustained over time
•Safety problems may emerge
•Value of information approach can help choices between (i) adopt, (ii) delay and trial, (iii) adopt and trial (CED). Risk sharing can enhance value of (iii).
•Real challenge is not HTA but budget impact
•Can we tackle high upfront costs of a cure that was cost- effective using the appropriate cost-effectiveness threshold?
•Three possible routes?

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Ways forward (1): “Pay for performance1”
•Eliminate any perverse incentive to prioritise investment in repeatedly administered therapies over one-time treatments.
•Pay for performance with periodic payment as long as gene therapy “works”1.
•At its simplest (i) annual health check (still cured?) (ii) runs for several years / lifetime
•But many issues in structuring a PBRSA2
•Transaction costs
•Patient “churn” – does money follow the patient?
•May not be a simple “works” yes/no? measurement / threshold issues
•Dying of something else… Source: 1Brennan and Wilson (2014). 2Garrison et al (2013)

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Ways forward (2): “Amortisation”
•Payment models that spread the potentially high upfront costs over the time during which benefits are realized, which would allow the cost of treatment to be amortised1 over many years.
•This is how capital equipment is treated. But:
•Still pay upfront for uncertain benefit
•It meets accruals principle but does it meet the prudence principle?
•They make the point that a third party could get involved. This is equivalent to leasing e.g. when we buy a car. But with a car we get a warranty and we know the residual value over time.
•A medical equipment alternative is that the innovator retains ownership of the “asset” and contracts to provide a flow of services - P4P! Source: 1 Gottlieb, S., & Carino, T. (2014).

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Ways forward (3): Innovative financing mechanisms
•In global health there are examples. Notably, the International Finance Facility for Immunisation, (IFFIm) which raised US$bns1.
•Donors pledge up front and payback over time. Upfront money is spent by LICs on vaccines – equivalent to a “cure”
•But inserting a third party between manufacturers and payers / insurers to make upfront payments is problematic:
•It is efficient for innovators to bear some if not all of the performance risk
•Insurers are already pooling patient population risks Source: 1 Larry Elliot (2006).

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Summary points
•Regenerative medicine shows potential
•Might even provide cures in some cases.
•Only four treatments have had regulatory approval in Europe so far.
•Only one of them is reimbursed centrally, in four European countries. Turned down by HAS.
•In HTA terms, “cures” are, in effect, disease modifying therapies for chronic diseases with the associated problems
•High upfront costs might pose a barrier to adoption.
•PBRSAs / MEAs offer a way forwards
•Accounting changes “amortisation” and “innovative financing mechanisms” may (?) offer a way forward

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References
•Brennan, T and Wilson, J. (2014). The special case of gene therapy pricing. Nature biotechnology,32(9):874-876.
•Dendreon (2014). Dendreon Announces Plans to Make PROVENGE® Commercially Available in Europe. Available at: http://investor.dendreon.com/releasedetail.cfm?ReleaseID=829491
•Garrison, L.P., Towse, A., Briggs, A., de Pouvourville, G., Grueger, J., Mohr, P.E., Severens, J.L., Siviero, P. and Sleeper, M. (2013) Report of the ISPOR Good Practices for Performance-based Risk-sharing Task Force. Value in Health. 16(5), 703-719.
•Gottlieb, S., & Carino, T. (2014). Establishing new payment provisions for the high cost of curing disease. America Enterprise Institute.
•HAS (2010) Transparency Committee. Opinion. Chondrocelect. Available at: http://www.has- sante.fr/portail/upload/docs/application/pdf/2012-11/chondrocelect_ct_8020.pdf
•Larry Elliot (2006). Brown launches £2.1bn bond issue to vaccinate 500 million children. The Guardian. Available at: http://www.theguardian.com/business/2006/nov/07/politics.internationalaidanddevelopment
•Mason, C., & Dunnill, P. (2008). A brief definition of regenerative medicine. Regen. Med, 3(1), 1-5.
•McEwen Centre for Regenerative Medicine. What is regenerative medicine? Available at: http://www.mcewencentre.com/discoverandlearn/regenerativedetails.php
•Pharmaletter (2014). Chiesi and uniQure delay Glybera launch to add data. Available at: http://www.thepharmaletter.com/article/chiesi-and-uniqure-delay-glybera-launch-to-add-data
•Reuters (2014). TiGenix : licenses exclusive marketing and distribution rights for ChondroCelect to Sobi. Available at: http://uk.reuters.com/article/2014/04/03/idUKnHUGdBXH+77+ONE20140403
•Science and Technology Committee (2013) Regenerative medicine report. House of Lords. London

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To enquire about additional information and analyses, please contact Professor Adrian Towse at atowse@ohe.org. To keep up with the latest news and research, subscribe to our blog, OHE News. Follow us on Twitter @OHENews, LinkedIn and SlideShare. The Office of Health Economics is a research and consulting organisation that has been providing specialised research, analysis and expertise on a range of health care and life sciences issues and topics for over 50 years. OHE’s publications may be downloaded free of charge for registered users of its website. Office of Health Economics Southside, 7th Floor 105 Victoria Street London SW1E 6QT United Kingdom +44 20 7747 8850 www.ohe.org ©2014 OHE