Prof Alex Faulkner Centre for Global Health Policy Tuesday 8th November 2016, Jubilee Room, House of Commons Regulating and paying for regenerative medicine products in the NHS – challenges and opportunities Prof Alex Faulkner Centre for Global Health Policy

Outline Flexibilities in regulation that are part of attempts to accelerate access to market of new products -potential impact on NHS innovation and patients Debates about how to pay for such products when the evidence base is necessarily still being developed.

The product regulatory environment Advanced Therapy Medicinal Products ATMPs Tissues and Cells HTA MHRA Pharmaceuticals Medical Devices

Key parameters Scientific and effectiveness uncertainty Standard of care? Data poverty High cost Curative? Disruptive to NHS?

Pathways to market- centralised EU systems and data requirements Pharmaceutical Advanced Therapy Medicinal Product - cell therapy; gene therapy; tissue-engineered product Medical device HOW MUCH FLEXIBILITY? UK pharma ‘Specials’; Unmet need; ‘Wait-and-see’ risk-sharing hybrid marketing authorisation; Rare diseases/orphans → ‘experimentalist’ adaptation of governance?

Medicines pathways - EU ‘Licensing flexibilities’ for ‘unmet need’ and public health emergency: Conditional approval Exceptional circumstances Accelerated assessment -> ‘Medicines Adaptive Pathways for Patients’ (MAPPS) Mapps a non-legal category

‘Compassionate use’ (Hyry et al, 2015) Allowed by Pharmaceutical Directive 2004 50 programmes notified to EMA 2006-15, - 40% relate to ‘Orphan’ drugs/’Rare disease’ - pre-approval, pre-reimbursement (Hyry et al, 2015) Once orphan gets MA, secured statutory monopoly for 10 years. Reimbursement varies, in fact France has intro system where hosp pharmacies can pay full price (or + premium) for such treatments.

Hospital-based pathways One-off or personalised nonroutine applications ‘Hospital exemption’ (ATMP), or ‘Special’ license (Medicines) , allows treatment and -> data for clinical trial ? in-house medical device exemption Specials most used in UK, other euro countries using HE more widely, controversial cuz fear can distort market, and EMA has doubts about stem cell standard control

‘Medical device’ pathway e.g. closed system intra-operative cell processors transplant e.g. for reconstructive surgery multiple clinical uses Subs manipulation/homologous use criteria

Flexible pathways to healthcare adoption/clinic - ? ‘Promising innovative medicine’/ ‘Early access to medicines’ (MHRA) NICE valuation methodology and assessment decisions NHS Executive commissioner schemes Individual patient funding

Early Access to Medicines EAMs Government Strategy for Life Sciences. ‘aims to give patients with life threatening or seriously debilitating conditions access to medicines that do not yet have a marketing authorisation when there is a clear unmet medical need’ Designation as a PIM: ‘Promising Innovative Medicine’

First ‘PIM’ designation -for a cell therapy product for the treatment of cancer on 8 September 2014. -Cancer immunotherapy - -DCVax-L (from NW Bio) covers all malignant gliomas, which including both Glioblastoma multiforme (the most severe grade) and less malignant grades PIM opens way for EAM scheme

NICE exploration of applicability of methods to RM “…demonstrate the versatility and adaptability of NICE’s approach to appraising health technologies to enable appropriate consideration of these innovative treatments.” …recommends that NICE continues to further develop the ways in which uncertainty can be quantified and presented to its decision-making committees.’

furthermore… ‘Where there is a combination of great uncertainty with potentially very substantial patient benefits, innovative payment methods may have a key role to play in managing financial risk … (https://www.nice.org.uk/News/Press-and-Media/nice-publishes- report-on-approaches-to-assessing-innovative-regenerative- medicines) 29 March 2016

Payment methods/ uncertainty Projected benefit high (10 QALYs) + v. high uncertainty: -> ‘The lifetime leasing method of payment … was viewed with considerable interest by the Panel. .. where a monthly fee is paid for the duration of treatment benefits (until death) greatly reduces the decision uncertainty… It is important to note that… the asset in question is the health gain delivered rather than the CAR T-cell therapy itself.’

NHS service commissioning

NHS England commissioning Alternative, conditional gateways to adoption: ‘Commissioning through Evaluation’ scheme ‘Risk-sharing’ schemes explored ‘Specialised services’ (NB ‘funding experimental and unproven treatments’ part of Specialised Commissioning public consultation Oct 2016) NHS Tariff innovations? CCGs

Risk-sharing RM example currently being used in Italy for Strimvelis (GSK) (for ADA-SCID , severe immunodeficiency; EMA license as gene therapy medicinal product/ ATMP May 2016) Italy has a good history in risk sharing. Currently about 90 therapies reimbursed in this way. Medical tourism?

Converging Pathways ‘Early access schemes’ ‘Managed Entry Schemes’ ‘Conditional Authorisation’ ‘Adaptive Pathways’ ‘Risk-based approach’/’Risk-sharing’ payment NICE/NHSE coordination NICE/MHRA coordination Proliferation of schemes…bridging the market authorisation/clinical application boundary

From Accelerated Access Review Final Report 2016

Summary – growth of provisional, converging pathways Legal/market regulatory gatekeeping Converging: legal easing; broadening criteria Adoption gateways ATMP Hospital Exemption Adaptive licensing ‘Specials’ license (UK only) Orphan designation Exceptional Circumstances Accelerated Assessment Medical device -Early Access Scheme/Promising Innovative Medicine (PIM) assessment -Adaptive pathways -Conditional approval -Risk-sharing -Innovative payment systems ‘Parallel review’ (Value-based assessment ) NHS Executive special clinical service schemes NHSE Commissioning through Evaluation Multiple individual patient funding requests

Issues: To what extent is patient access and public health promoted? Rare disease applications Exceptional ‘compassionate’ use route favoured by SMEs ‘Unmet need’ ‘Special’ and exempt patient access routes Provisional reimbursement Needs-driven? Generally not population-wide at the moment