Comment

Orphan medicines: Special treatment required?

Leela Barham and Julia Manning of 2020health discuss ways of improving access to orphan drugs.

Medicines that are developed to treat conditions with a very low prevalence are usually described as ‘orphan’. The European Commission brought in legislation to encourage research and development (R&D) into rare diseases over a decade ago and there are now 68 medicines designated as ‘orphan drugs’ and licensed for use. Given that the time taken to bring a product successfully to market is somewhere between 10 to 14 years, it’s no surprise that more orphan products are coming to market now. However, with the NHS under financial pressure, it is also the time to ask about their value for money.

A rare disease is defined as a disease that affects fewer than 5 in 10,000 people. That’s also a requirement for orphan drug designation in the European Union. Therefore inevitably the drug is not for large numbers of patients, and in the case of very rare diseases, treated with so-called ‘ultra-orphan drugs’, it may even be for just a handful of patients. Research from 2020health has reviewed the evidence, and drawn on interviews with a range of stakeholders, and has found that access for those small numbers of patients to orphan drugs is inconsistent across and within the UK. That refl ects the differences in processes to decide whether or not the NHS will pay for orphan drugs.

Part of the decision making process for funding is clear. In England the National Institute for Health and Clinical Excellence (NICE) looks at selected new orphan drugs, in Scotland it is the Scottish Medicines Consortium (SMC) and in Wales it is the All Wales Medicines Strategy Group (AWMSG). Each agency uses a slightly different process and decision-making framework, but all draw on the cost per Quality Adjusted Life Year (QALY) to inform their decisions. With some (but by no means all) orphan drugs having a high cost (with a median cost of around €32,000 per patient per year) value for money can be challenging to demonstrate.

Those prices are partly driven by the practical challenges in recruiting patients for trials from small patient pools, as well as the typical risks in R&D, and the need for companies to deliver commercially attractive returns. But value for money is only one part of the decision; this has led to a wider framework being used in the case of ultra-orphan drugs by the soon to be dismantled Advisory Group for National Specialised Services (AGNSS). For example, they look at the value that products may bring to wider society. AGNSS was an English group to help inform commissioning decisions for services that would be used by less than 500 people across England. That group not only looked at the evidence, but also directly commissioned using top sliced funds.

The workload of these agencies on orphan drugs differs however. None (to date) have assessed all licensed orphan drugs in all their indications, and NICE has looked at the least, considering 18 indications from the 75 indications possible for the 68 licensed drugs with orphan drug designation. That compares to 56 indications for the SMC and 51 for the AWMSG. AGNSS considered two new orphan drugs, but (at the time of writing) public decisions from ministers based on their advice have not been made.

That means that there are still indications and orphan drugs that fall between the gaps in all three agencies’ recommendations, and it is then up to regional/local decision makers (whether that’s Primary Care Trusts in England, or Local Health Boards in Scotland or Wales) to review the evidence to guide their decisions. This process is particularly opaque.

It’s also not clear that all parties agree with the decision making approaches. Some are frustrated when there is no guidance, others that the process is not necessarily patient focused and/or doesn’t ensure that the clinical expertise required for these rare conditions is available and brought to bear.

There is now an opportunity to build on a number of changes either planned or underway to improve access to orphan drugs.

The UK, as with other European countries, is developing a strategy for rare disease.

NICE will take on AGNSS’ remit for high-cost, low-volume drugs. Both will include a focus on access to drugs that can make a difference to quality of life and in some instances longevity of those with rare diseases too. 2020health believes that there is an opportunity to build on the AGNSS approach and move to a wider framework for assessing orphan drugs, and that patients would benefi t if the devolved nations moved to a more consistent basis for their recommendations.

That would be proportionate – making the best use of limited clinical expertise, patient organisation input and contributing towards a sense of fairness that patients and the public desire. The move to Value Based Pricing (VBP), where drug prices should be more closely tied to their value, needs further refl ection for its applicability to orphan drugs, not least as VBP needs to ensure that incentives for future R&D remain. To blunt incentives when there has been a clear drive of the regulatory changes introduced in 2000 would seem frustrating at best, pointless at worst.