Cracking the code: How can the UK prepare for gene therapy?

Mar 22, 2017 | By Greg Manuel | Posted in NHS

With the first gene therapies beginning to hit the market, Greg Manuel asks how industry, NHS England and NICE can work together to ensure that patients can reap the benefits of these potentially life-changing treatments.

A few years ago the idea of editing a person’s genes to treat disease would have seemed like something out of science fiction. But the future has arrived, with the first treatments based on editing the human genome beginning to hit the market.

Yet a side effect of these treatments might well turn out to be a few headaches for regulators, manufacturers, health services and taxpayers, as a recent report from the Institute of Clinical and Economic Review and the Office of Health Economics makes clear.

To understand why gene therapy is generating both excitement and concern across the globe you need to understand how it works. In simple terms, gene therapy uses a viral vector to change the expression of a person’s genome with the aim of preventing, treating or curing disease. This process of ‘editing’ out faulty genes raises the prospect of creating a whole class of preventative and curative medicines, potentially for thousands of genetic disorders.

A host of advances have made this possible. The development of genomic technologies like CRISPR/Cas9, scientific progress in figuring out what different genes actually do and significant investment from industry and academia have all been integral.

It’s the potential of these scientific advances to deliver truly transformative ways of treating disease that makes gene therapy so disruptive. Gene therapies that can cure or prevent diseases, potentially on a ‘once and done’ basis will not only command a premium price tag but will also necessitate the wholesale redesign of existing treatment pathways to deliver a new form of treatment. The question is, when the NHS is already struggling to make treatments available, can the health service adapt to this new class of medicines? While there are no easy answers to this question, the NHS is potentially well placed to lead the world in coming up with them.

For one, the UK is already recognised as a world leader in genomics, thanks in no small part to the former Prime Minister David Cameron’s commitment to the issue. Investment in the 100,000 genomes project, the launch of the Cell and Gene Therapy Catapult and the UK’s enviable life-science infrastructure mean that the NHS has earned an early lead here.

Similarly, the US Food and Drug Administration and the EU have to date both failed to articulate a coherent framework for the regulation of genomic medicine. As such, Brexit might provide the UK with the opportunity to develop a new approach to medicines regulation, tackling barriers to research that have hampered genomic research in the EU in recent years.

But even with these advantages, challenges remain. For gene therapy the most pressing issue is establishing the long-term effect of these therapies with only short-term data. In sum, how do you show that gene therapies can unlock savings for the economy and healthcare system by curing or preventing disease when you have only short-term data to go on?

Payers concerned about shouldering long-term risk will highlight claims of waning efficacy to make just this point. Take, for example, a recent clinical trial for people with inherited blindness at the University of Pennsylvania. The study found that after achieving improvements in sight, patients’ vision began to deteriorate again one to three years later. Similarly, payers might also point to concerns about the durability and safety of the viral vectors that are actually used to deliver treatment as another barrier to securing full reimbursement.

NICE is acutely aware of uncertainty about longevity, highlighting the challenge of extrapolating from small single-arm trials to long-term patient outcomes in its own paper on gene therapies published last year.

There are a number of productive approaches to overcome this issue however. For example, early discussions with regulators and payers on ways to make trials as robust as possible and opportunities to continue to generate data after launch should be pursued. The UK’s Early Access to Medicines Scheme is a particularly good model of industry and regulators working together to support real world data collection for promising new medicines pre-marketing authorisation.

Putting aside issues with appraisal, payers will also be concerned about the affordability of gene therapy. As the ICER/OHE report makes clear, the potential budget impact of gene therapy will dwarf existing challenges at a time when payers are already grappling with constrained health budgets.

Last week, NICE and NHS England confirmed two ways that they plan to deal with this issue. For NICE’s standard HTA process, they’ll require companies to negotiate with NHS England on price if NICE estimates that any new cost-effective technology will cost the NHS £20 million or more in any of its first three years.

Further restrictions were also confirmed on the way treatments for very rare conditions are assessed for use in the NHS. Yet they do offer a glimmer of hope for gene therapies used early in life. Treatments that deliver 30 or more incremental QALYs would face an effective threshold of £300,000 – somewhat higher than for other treatments. Whether this flexibility is enough remains to be seen (early noises from industry and charities suggests it won’t be), but it does establish the principle of differentiation. Again, the challenge will come in generating sufficient evidence of long term health gain from small trials with limited follow up to satisfy payers.

While there’s been a wave of consternation in response to these proposals and the debate is still to be had over whether cost-effectiveness thresholds are even appropriate for orphan and ultra-orphan treatments, the introduction of the 30+ QALY gain weighting is potentially encouraging for gene therapies.

There are also some signs of industry, NHS England, NICE and commissioners getting round the table to come up with innovative risk sharing and outcomes based market access agreements, such as a recent Managed Access Agreement for Duchenne muscular dystrophy.

NHS England is also making some positive noises about enhancing its ability to agree just these sorts of deals as recommended by the Accelerated Access Review. While developments like the Manchester Memorandum of Understanding open the way to pilot population based access schemes too.

With healthcare budgets unlikely to expand in coming years and a golden age of genomic medicine on the horizon the issue of how patients can access these cutting-edge therapies isn’t going to go away. If patients are to reap the benefits of genomic medicine this is one exam question that ministers, the NHS and taxpayers can’t afford to dodge.

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