Early Access to Medicines Scheme – terrible twos or maturing nicely?
The Early Access to Medicines Scheme (EAMS) has reached its second birthday (April 2016). The scheme aims to provide patients earlier access to drugs before they are licensed but only when the preliminary data suggests that the balance of benefit and risk is positive. Not only that, there also has to be an unmet need to treat a condition for a life threatening or life limiting disease. After two years, is the scheme maturing nicely, or facing the terrible twos?
A reminder of the scheme
The scheme has three key steps:
• Step 1: Companies can voluntarily apply for a Promising Innovative Medicine (PIM) designation. Companies have to put together a package of evidence and pay a fee to apply.
• Step 2: If companies are successful in gaining a PIM designation they can then go on to apply for a full EAMS scientific opinion (SO). A positive EAMS SO results in a suite of documents from the Medicines and Healthcare products Regulatory Agency (MHRA) to support clinicians in deciding whether or not to prescribe – within existing laws and governance frameworks for unlicensed prescribing - before the product secures the marketing authorisation (MA). Companies pay a fee for the SO and provide the drug at no charge to the NHS during the EAMS period.
• Step 3: The broader system prepares for commissioning the use of the drug. This includes the National Institute for Health and Care Excellence (NICE) and NHS England looking at the product.
The underlying premise for the scheme is patient focused; patients may benefit when access is allowed earlier than usual.
Thirteen Promising Innovation Medicines so far…
There have been 21 applications for PIMs, with 13 of those leading to a PIM designation (figure 1).
Figure 1: PIM applications, up to April 2016
Source: Data from MHRA
PIMs to date (in the public domain – MHRA does not reveal the details for PIMs, but companies can choose to) have dominated in cancer (Table 1).
Table 1: PIMs in the public domain, up to April 2016
Sources: PharmaTimes, Rexgenero, Northwest Biotherapeutics, Pharmaphorum and MHRA on current SOs and expired SOs accessed 20 Apr 2016
Note: nsclc = non-small cell lung cancer
…translating into eight Early Access to Medicines Scheme Scientific Opinions
Not all those companies with a PIM will necessarily go straight into the full EAMS SO. They can take up the opportunity of a (no charge) meeting with MHRA to discuss their application before incurring the fee and putting the application together. They can also take the view that waiting for further evidence might be helpful, or they can simply choose not to continue. The latter may well reflect concerns about cost; whilst the fee for the full EAMS SO has been reduced from £29,000 to £25,643, other costs exist. These include provision of the product at no charge to the NHS, as well as providing the infrastructure needed to support delivery of the product to the NHS.
To date, there have been nine applications for the full EAMS SO. Eight of these have translated into a positive EAMS SO (figure 2).
Figure 2: EAMS applications, up to April 2016
Source: Data from MHRA
Most of those receiving the positive EAMS SO so far are in cancer (Table 2).
Table 2: EAMS SOs up to April 2016
Source: Data from MHRA on current SOs and expired SOs accessed 20 Apr 2016
Note: nsclc = non-small cell lung cancer
Delivering a speedy opinion and faster access for patients
The focus of EAMS is on speeding up access when there are particularly promising drugs, but with some careful consideration when evidence is still in development. MHRA set out a timetable for how quickly they could provide a full EAMS SO. So far, they’ve been able to meet that. They’ve also been able to use their fastest timetable – 75 days – in the majority of full EAMS SO applications (figure 3).
Figure 3: Speed of MHRA EAMS SO’s
Source: MHRA response on 18 Apr 2016 to a Freedom of Information request
This has also translated into access before licensing for patients. At best, this has been over 120 days faster than the full MA (figure 4). This is still long short of the potential 12 to 18 months that has been discussed; naturally though it does depend on the company, the MHRA, and the evidence so these may have been overly ambitious goals in practice.
Figure 4: Number of days drugs available before MA through EAMS, up to April 2016
Source: Analysis of MHRA data on current SOs and expired SOs
A systemwide perspective; from EAMS to routine commissioned use for patients
Getting an EAMS SO is not the final goal; this helps provide access before the MA, but doesn’t solve the conundrum of value for money (that NICE and other Health Technology Assessment (HTA) agencies worry about), nor the tension with affordability (that NHS England and other payers worry about). A product could become unavailable (or at least very difficult to access through individual funding requests or private prescription) if it is not recommended by HTA agencies or not routinely commissioned by a payer.
Just as with MHRA giving a speedy opinion, in a world where there can be reticence to prescribe whilst awaiting an HTA opinion, a speedy appraisal can influence access after the EAMS SO period is finished.
In the case of the first product to go all the way through EAMS, MSD’s pembrolizumab for advanced melanoma, MSD was also able to secure a fast track NICE appraisal – the fastest on record – as well as a 30-day implementation timetable for the positive NICE recommendation. It’s hard to know how much faster patients were able to access pembrolizumab for melanoma on a routine basis than they would have without EAMS, but my bet would be on months and not weeks.
So far, NICE has come out in favour of three EAMS products (Sacubitrial/valsartan, pembrolizumab in advanced melanoma with and without ipilimumab, and nivolumad in advanced melanoma), but not in the case of nivolumab for advanced lung cancer in an Appraisal Consultation Document. The remaining four positive EAMS SO products’ appraisals are still in progress at NICE.
Such differences in opinion between the regulator and a HTA agency on use of a drug might be technically understandable – MHRA does not need to concern itself with value for money considerations – but is likely to feel frustrating for patients and companies. MSD offered a Patient Access Scheme (essentially a confidential discount on the price of pembrolizumab) which likely helped it achieve the NICE yes alongside the PIM and EAMS SO from MHRA. BMS has tabled a PAS for nivolumab for advanced lung cancer which could help sway NICE. The sticking point might be the scale of the discount; after all, BMS will want to get a return for the innovation it’s brought to patients. That’s natural given the commercial nature of the company.
The debate on whether NICE’s threshold is enough to do this at a level that is both reasonable for the NHS and taxpayers, yet acceptable for companies is likely to remain – and patients are in the middle of this. EAMS might focus this debate; products with a positive EAMS SO are definitively ‘innovative’ so the argument cannot be that they are not innovative, but rather that innovation is too expensive. That could be too expensive because of the price, or the other perspective would be that the system is not willing to pay enough.
A cancer focus remains
Cancer, just as it did after the first year, still dominates. That’s likely to reflect broader drivers than the scheme itself; cancer is a key focus of some the world’s biggest pharmaceutical companies and it’s the large companies who may well have the deep pockets and resources available to take up EAMS.
Could funding help increase interest in the scheme?
The cost of EAMS – not so much the fees but the costs of providing free stock and infrastructure – has been a continued concern for industry. It could be putting off smaller companies in particular from taking part in EAMS and providing earlier access to patients that could be treated with the products they make. The dominance of big firms lends some weight to that concern (although other companies may have sound reasons not to progress to EAMS that are unrelated to money).
An independent review of EAMS has recommended that funding for companies is considered. Could that help encourage more companies to take up EAMS? Funding for EAMS drugs could be taken forward in the Accelerated Access Review (AAR) – an independent review focusing on speeding up adoption of innovation across the NHS in England – but we’ll have to wait until after the EU referendum to find out. Unfortunately it seems that even though the AAR is all about speed and was announced in November 2014 it will take 19 months to report.
For more indepth analysis of the progress of EAMS, please find the full report here.
Leela Barham is an independent health economist and policy expert.
Follow her on Twitter: @leelabarham