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But just when is access really early, and what are the options for companies to consider in 2015?

By Leela Barham on Mar 4, 2015

Early access to medicines continues to be a hot topic, in part, because patients themselves have been pointing out that they want access, accepting the risks inherent in taking experimental treatments, even before formal licensing.  This underpins the ‘right to try’ debate in the US and the Halpin Protocol in the UK. But ‘timely’ access isn’t just about licensing; Health Technology Assessment (HTA) agencies and payers can slow access too. 

When is early access, really early?

Early for regulators in recent debate has meant access before formal licensing, simply because it can take a long time to reach the point where the company has the dossier needed to convince regulators of the safety, quality and efficacy of their product. Although, it’s worth remembering that the centralized procedure in Europe was in part, introduced to speed up patient access across the region. There’s also scope for even the usual marketing authorization to be faster as a result of adaptive trials.

Early in the context of HTA, or decisions from payers, is less straightforward. HTA agencies are concerned with value for money, and often influence reimbursement (although arguably indirectly influence price too). Payers consider price as well as reimbursement, and their approaches vary, including negotiations on price – which can take time.

Plus when price comes in, it’s both companies and the payers who impact on the speed at which a final price for that market comes through, because increasingly companies will know whether their price will be seen as good value, or not, and hence how much negotiation there will be over the pricing and reimbursement status of their product or the potential reaction of a HTA agency. Going in with a lower price, whilst not necessarily commercially attractive (or even possible in order to recoup R&D and to help fund future R&D), may make it faster to get through the price and reimbursement process.

Both HTA and payers are generally making their decisions post license, although in fairness, they are often horizon scanning and do plan ahead.

Speeding up access pre-license

The options open to companies for faster access before getting a license have been increasing over the years. Here are just a few:

France

Companies can apply for an “Autorisations Temporaires d’Utilisation” or a temporary authorisation for use.  This option has been open to companies since 1994. ATU is an option when there is a public health need, a lack of suitable alternatives, and when it looks likely that there will be a benefit. ATU is either on the basis of named patients, or a cohort of patients. ATU has been designed so as not to duplicate or slow clinical trials, nor act as a loophole avoiding scrutiny through marketing authorization with the expectation that companies will, in a reasonable amount of time, go ahead with an application. During the ATU period though, patients can access earlier than they otherwise would.

It seems that companies have made good use of this option; between 2005 and 2010 77 ATUs were granted. Access was faster, and companies seemed to achieve a 12% price premium.

UK

Companies can apply to the Early Access To Medicines Scheme (EAMS). The scheme has been open not even a year so far. Similar to the ATU scheme, the scheme is intended for medicines that treat a life-threatening or seriously debilitating condition with high unmet need.

It’s too early to say much about the impact of EAMS, although there are 3 companies who have passed the first step and achieved a Promising Innovative Medicine (PIM) designation. Next is assessment for the Early Access to Medicine scientific opinion. However, even with that, as it stands companies will need to provide their product at no charge to the NHS.

US

The US Food and Drug Agency (FDA) has a whole raft of options for faster approval.  They include; breakthrough therapy designation (introduced in 2012), fast track designation (1997), accelerated approval (1992), and priority review (1992). Priority review, for example, shortens the time for FDA to consider the product from 10 months to 6 months.

Staggered licensing – faster for some, but not all patients

The Adaptive Licensing (AL) pilot underway with the European Medicines Agency (EMA) takes quite a different approach to earlier access - under this pilot companies can apply for licensing as a ‘staggered’ approach instead of all or nothing. They can put in for consideration of a licensing for a sub-group of patients, and then in collaboration with the EMA decide on the approach to evidence generation, needed to inform future decisions in order to expand the license to a larger patient population. The result could well be earlier access for some patients, but not necessarily all patients who could benefit from the new medicine. AL is still young, not even a year old, with the pilot announced in March 2014.

Companies can also still consider the options of a conditional marketing authorisation – granted when there is unmet need and with application for the full license following the gathering of further data – or a marketing authorisation in exceptional circumstances – where getting full data is unlikely to be possible given small patient numbers. They can also consider accelerated assessment, with an opinion on their product in 150 days, rather than 210.

Speeding up access post license

Speeding up HTA

Speeding up HTA has been a focus of a few of the key agencies; for example, NICE introduced the Single Technology Appraisal (STA) approach to speed up their guidance back in 2005. Over time, HTA does seem to be speeding up. Speeding up HTA is also part of the drive behind increasing co-ordination between EMA and HTA in Europe.

A possible new option in England – Commissioning through evaluation

There might be the potential for access to be earlier as a result of a new Commissioning through Evaluation (CtE) (or even Evaluation through Commissioning since both names are bandied about) approach in England. Evidence generation would feature as a condition of reimbursement, and just as with AL, it could well be focused on access for a sub-group, with the results of evidence being used to inform decisions to expand use further, and hence increase spend by the NHS. Early here is likely to be earlier use versus waiting for the appraisal by NICE, tackling the issue of so-called NICE blight. But it might just be any access at all, rather than how fast it takes place. So far it’s only been applied to devices and procedures, but there’s scope for it to apply to medicines too.

Early access – licensing and reimbursement

Debate recently has started to link the early access debate for both licensing and pricing and reimbursement. Hans Georg Eichler, from the EMA, has raised the prospect of complementing the AL approach with a managed entry approach to reimbursement too. Speculation includes the development of adaptive pricing.

Early access: some pointers

• Keep an up to date mapping of all the options, even if some won’t be right for your product you’re going to launch soon, or your wider portfolio in R&D now, the options are changing and being adapted as agencies ‘learn by doing’
• Keep an open mind, you might be able to develop a new option and explore it with some of the key agencies. Access has never been so dynamic!
• Plan early and take up those options for early advice that are available and that you can afford, not only in fees for advice but take into account the time that you on the company side, need to put in to get the most out of them
• Talk to patients and their representative organisations. Don’t keep the discussion just within the regulatory agencies, or the HTA agencies, make sure you talk to patients too. It is about meeting their needs, after all, and they will help inform perspectives on acceptable risks and what outcomes are important to them
• Close down options quickly that just won’t work. Commercial reality has to come in, and whilst making sure that you at least consider all the options, knowing when to cut your losses and move on when one access route just won’t work for your next launch is crucial too.

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Leela Barham is an independent health economist based in the UK. She can be reached at leels@btinternet.com