Considerations around ‘value’ assessment for gene and cell therapies in rare diseases was a theme addressed by several speakers, to close the 1st day of a CAR-TCR Europe 2020 Summit meeting in London, yesterday.

Three different viewpoints were provided touching on reducing the uncertainty when engaging National Payer Authority/Technology appraisal bodies; exploring ‘incremental value’ strategies and their positioning with Payers; and risk sharing approaches being adopted with Payers that are changing the nature of the relationship / partnership with manufacturers. 

Given the focus of the meeting, CAR-Ts were used as an analogue but the views and considerations were applicable to the broader gene and cell therapy sector.

We’re open for dialogue; we recognise the high unmet need; we get the fact that there’s a sparsity of data and that its not always feasible or ethical to do comparative trials.  However, manufacturers need to think harder about decreasing the uncertainty being presented to payer authorities.  These were the overriding messages outlined by Deborah Morrison (Principal Scientific Advisor, National Institute for Health & Care Excellence - NICE).  Uncertainties over efficacy, durability of response, adverse effects, comparators and the approach to economic modelling, increase the clinical and financial risks to healthcare systems, which in turn leads to attempted de-risking through price reductions and  lengthy negotiations with inevitable delays in decision making.  No one really wants this.    

The advice to manufacturers was three fold: 1. Provide clear justification of economic modelling assumptions and model structure (to reduce structural uncertainty); 2. Provide sensitivity analyses and scenario analyses (to support quantification of the uncertainty); 3. Put forward risk sharing schemes (to reduce the decision uncertainty).

NICE itself is dealing with uncertainty in a number of ways:

- Through price setting

- Outcomes based Patient Access / Managed Access schemes

- Commercial Access Agreements with Life Sciences companies

- Making a recommendation for a new product while further data is collected (data collection agreements) i.e. recommendation pending 

- Recommending a new cancer product through the Cancer Drugs Fund (UK)

- Recommending a technology for use despite the uncertainty 

‘Consider the incremental value strategy to Payers’, was the advice put forward to manufacturers by Aura Mackenzie (Senior Director, AVES, Market Access, Bluebird Bio).  Using CAR-Ts as an example, whether focussed on a first in class or subsequent generation asset, Aura outlined several possible ‘incremental’ value propositions for cell therapy manufacturers, to assess:   

1. Shorter vein-to-vein time - faster manufacturing may have a differential value in sub sets of patient populations especially when linked to the rate of disease progression.  This may be of particular importance sub-nationally with Centres of Excellence, to justify Hospital formulary inclusion in discrete populations. 

2. ‘The armoured car’ approach - here extra ‘Car’ architecture is valuable if it translates into tangible safety and efficacy benefits.  To payers, better T-cell activation is valuable if it leads to improved overall survival; a better adverse event profile is valuable, if it translates into fewer hospitalisations without compromising durability of response.

3. Value by line of therapy - this is a major consideration for new targets.   Target antigen failures are a growing issue.  Positive data outcomes may be more challenging to generate in 4L use vs. 3L.  Equally, 3L use may offer a more attractive commercial opportunity but may require H2H data.  These issues need to be thought through, to shape investment and value proposition focus. 

4. Market Payer archetypes (economic vs. clinical drivers).  Using the example of allogeneic CAR-Ts (‘off the shelf’ products), potential cost savings may not be enough in indications with established autologous CAR-T products, when dealing with clinically driven HTAs (e.g. Germany) especially if the allo’s are associated with poorer efficacy and adverse event profile. 

Concluding a trilogy of presentations, Omar Ali (Visiting Lecturer, Value Based Pricing & Former Adviser to NICE, Unicersity of Portsmouth) put forward the premise that payers are not just worried about one drug, it’s the queue of drugs behind it that keeps them up at night.  Uncertainty is only going to increase especially with the gene and cell therapy area, ‘blossoming’.  This is compounded by the fact that many of the smaller biotechs developing assets or tech platforms have a limited understanding of access and reimbursement pathways.  

Value Based Agreements (VBAs) - where uncertainty is reduced by money being paid back including graduated rebates linked to efficacy thresholds not being met - are one example where the “solving for a problem” mindset is supporting greater access to innovative medicines.  Individual Financial Agreements (IFAs) including upper and lower cap thresholds and Indication Based Pricing (IBP) are two other mechanisms being deployed, to reduce the uncertainty for Payers.  With the latter, a drug with different indications may have a different value in each, given different levels of unmet need and value generated.  

Fundamentally, there is a difference between “I can’t afford it so reduce the price” versus “I can’t afford it, but how do we partner to come up with a different payment mechanism, as I acknowledge the unmet need or the QUALY gain is in the right ‘ball-park’.”  This requires early and regular dialogue with Payers, to support the right mindset of approach.  Perhaps the premise to put forward is that it’s not about ‘buying’  CAR-Ts per se, but rather  ‘buying remission’ and discussing how that influences the value being sought for patients and the broader healthcare system.