Earlier Patient Access – the UK Early Access to Medicines Scheme (EAMS)

Early Access to Medicines Scheme - 3 years on

The Early Access to Medicines Scheme (EAMS) was launched in the UK in April 2014, following a recommendation from the Ministerial Industry Strategy Group for an early access scheme, with additional input into the scheme's design via a public consultation and an expert group on the innovation in the regulation of healthcare under the Prime Minister's Strategy for UK Life Sciences (1–5).

The first Promising Innovative Medicine (PIM) designation was awarded in September 2014. A PIM designation is an early indication that a particular medicine is a candidate for the EAMS, with the potential to address an unmet medical need. The 3 PIM criteria include (i) a documented life-threatening or seriously debilitating condition and with high unmet clinical need; (ii) the medicine is likely to offer a major advantage over methods currently used in the UK; and (iii) the potential adverse effects of the medicinal product are likely to be outweighed by the benefits. To date, there have been 30 PIM designations awarded. The MHRA does not publish the PIM designation, although the company in receipt of a PIM is free to do so. Of importance, to facilitate interaction between a PIM designation holder and other stakeholders involved in patient access, the notification of a PIM designation by the MHRA includes contacts in UK National Health Service (NHS) and health technology assessment bodies. These contacts are also confidentially informed of the designation.

The first EAMS scientific opinion was approved in March 2015. The scientific opinion describes the positive benefit risk profile of the medicine, and supports the prescriber and patient in making a decision on whether to use the medicine before its licence is approved. The EAMS criteria build on those for the PIM designation, with the additional aspect that the company should supply a medicine manufactured to a consistent quality standard. During the assessment process (a day 75 or a day 90 timetable), a day 45 notification has been built into the scheme post launch, in order to facilitate the communication of a pending potentially positive EAMS scientific opinion. This notification flags to the NHS systems in the four UK countries that an EAMS medicine is likely to become available in a specific condition, so that necessary preparations might be brought forward, as appropriate.

A case study regarding the experiences and lessons learned from the first EAMS product, pembrolizumab, was published by the MHRA (Innovation: over 500 UK patients gain early access to new skin cancer treatment). Here, the company stated that “EAMS undoubtedly accelerated access to pembrolizumab for patients with advanced melanoma and demonstrates a world-leading example of how healthcare agencies and industry can work together to get treatments to patients more quickly” (6). From an MHRA perspective, the application process with pembrolizumab helped to identify and resolve some practical issues of running the scheme. These issues included the structure of the data requirements (including pharmacovigilance aspects), appropriate labelling, and further optimizing timelines. In this regard, the MHRA will be updating their guidance documents in the near future to reflect the lessons learned from the first 3 years of operation, strengthening the current procedures, and providing more comprehensive guidance for potential applicants.

To date, there have been 11 scientific opinions published, with the vast majority of opinions being in the oncology field (Tab. I). This is reflected in the PIM designations, where oncology has been a very strong focus. However, as the scheme has matured, applications for PIM have been received for a variety of conditions outside of cancer – including rare diseases – and it is expected that scientific opinions will broaden and cover other disease areas.

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Table I

Table of EAMS scientific opinions (first three years since launch)

Product	Company	Indication
Pembrolizumab	Merck Sharp & Dohme Limited	Treatment of unresectable or metastatic melanoma in adults.
Pembrolizumab	Merck Sharp & Dohme Limited	For the treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumours express PD-L1 as determined by the PD-L1 IHC 22C3 pharmDx Kit with a tumour proportion score (TPS) of greater than or equal to 50% tumour cells and who have not received prior systemic therapy or whose disease has progressed on or after platinum-containing chemotherapy. Patients who have not received prior therapy should be negative for EGFR sensitising mutation and ALK translocation. Patients whose disease has progressed on or after platinum-containing chemotherapy and who have an EGFR sensitising mutation or an ALK translocation should also have had disease progression on approved therapies for these aberrations prior to receiving pembrolizumab.
Venetoclax	Abbvie Ltd	Treatment of adult patients with chronic lymphocytic leukaemia in the presence of 17p deletion or TP53 mutations.
Nivolumab	Bristol-Myers Squibb Pharmaceutical Limited	Treatment of advanced (unresectable or metastatic) melanoma in adults.
Nivolumab	Bristol-Myers Squibb Pharmaceutical Limited	Treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC).
Nivolumab	Bristol-Myers Squibb Pharmaceutical Limited	Treatment as monotherapy of locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) after prior chemotherapy in adults.
Nivolumab	Bristol-Myers Squibb Pharmaceutical Limited	Treatment of patients with advanced Renal Cell Carcinoma after prior therapy in adults.
Nivolumab	Bristol-Myers Squibb Pharmaceutical Limited	Treatment of patients with Hodgkin or Non-Hodgkin lymphoma.
Osimertinib	AstraZeneca UK Limited	The treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) who have progressed on or after EGFR TKI therapy.
Sacubitril/valsartan	Novartis Pharmaceuticals UK Ltd	Treatment of heart failure (NYHA class II-IV) in patients with systolic dysfunction. LCZ696 has been shown to reduce the rate of cardiovascular death and heart failure hospitalisation compared to angiotensin-converting enzyme (ACE) inhibitor therapy.
Atezolizumab	Roche Products Limited	Treatment of adult patients with locally advanced or metastatic urothelial carcinoma after prior chemotherapy or who are considered cisplatin ineligible.

Evolving EAMS

Since its launch, the EAMS Government-Industry Stake-holder Task Group has regularly brought together key stakeholders from the bio-pharmaceutical industry, the NHS, and arm's-length bodies to inform the development of EAMS. This stakeholder group has produced EAMS “principles” and operational guidance describing the relationships between the MHRA, the National Institute for Health and Care Excellence (NICE), and NHS England (7). Ongoing work at the task force includes a focus on the opportunities and challenges of collecting real-world data in the NHS during the EAMS scientific opinion. The ability to collect such data offers an added benefit to companies involved in the scheme, with the potential to augment data collected from clinical trials. In this regard, the Office for Market Access at NICE offers companies the opportunity to have a supplementary meeting (NHS England are also invited) to discuss data collection plans during the EAMS period, where data may be generated to address uncertainties (8). It is expected that data collection during the EAMS scientific opinion will evolve alongside the already established pharmacovigilance aspects, providing a valuable opportunity to better understand the medicines' profile in the real-world setting, and complementing data derived from sources, such as clinical trials.

The UK Government's Accelerated Access Review (AAR) aims to speed up access to innovative drugs, devices, and diagnostics for NHS patients (9). The review was launched in March 2015, with a final report published in October 2016. The review makes recommendations to the government on reforms to accelerate access, and includes EAMS as a term of reference. The report builds on an independent review of EAMS (10). Statements in the report that specifically relate to EAMS include:

The government response to the AAR report is currently awaited.

Where to next?

The UK EAMS addresses a public health need to improve access to important innovative medicines, and has successfully facilitated the access to new medicines and new indications for hundreds of patients with unmet medical need. A number of proposals to strengthen the scheme since its launch have been implemented in the last 3 years. Exciting developments are to be expected as the scheme matures and the recommendations from the EAMS task force and the government response to the AAR are applied, which will further benefit patients and support innovation.