U.K.'s early access scheme working but challenges remain

LONDON – Two years after it was instituted, the U.K.'s Early Access to Medicines Scheme (EAMS) has succeeded in getting drugs to patients in advance of a formal marketing approval, but the aim that therapies arrive a year beforehand has not been met, and the fact the scheme is not funded makes it hard for small biotechs to participate.

"The aim was to give patients with life-threatening or seriously debilitating conditions access to medicines without a marketing authorization, where there is clear unmet need. It has succeeded in doing this," said Daniel O'Connor, expert medical assessor, licensing division, U.K. Medicines and Healthcare products Agency (MHRA).

To date, the MHRA has given scientific opinions on eight products under the EAMS scheme. As a result, prescribers are given confidence in the safety and efficacy and patients are getting access. There are "no major plans to change the scheme," but O'Connor said that based on comments and an independent review of EAMS, there will be some changes to guidance to provide more clarity on EAMS criteria and to try to extend the timeline by encouraging companies to make earlier applications.

O'Connor was speaking at a conference in London last week on "Accelerated Development and Access to Innovative Medicines for Patients." The event, which was jointly organized by the MHRA and the U.K. Bioindustry Association (BIA), included a review of EAMS from the perspective of different stakeholders that have been involved in its implementation.

In addition to the MHRA reviewing drugs that are yet to be licensed, EAMS involves accelerated appraisal by the health technology assessment body NICE (National Institute of Health and Care Excellence) and a faster route to commissioning in the National Health Service (NHS). Once NICE has issued positive guidance recommending the use of an EAMS product, the NHS must make it available within 30 days. (For drugs appraised in the standard process, the NHS has up to 90 days to implement NICE guidance).

To become a candidate for EAMS, a product must first be categorized as a promising innovative medicine, a status that is similar to FDA's breakthrough therapy designation.

Although stressing improved patient access, EAMS also has commercial intent, having originated in a life sciences Ministerial Industry Strategy Group. The BIA and the Association of the British Pharmaceutical Industry lobbied hard for the scheme, with an eye on the broader picture of reducing the time lag between regulatory approval, NICE's technology appraisal process and subsequent commissioning.

The first drug to go through EAMS was Merck & Co. Inc.'s first-in-class PD-1 inhibitor, Keytruda (pembrolizumab). It took longer than expected to get MHRA's positive opinion, which was secured only 130 days in advance of formal EU marketing authorization.

However, that was a meaningful outcome, with more than 500 patients receiving treatment for metastatic or unresectable melanoma between the MHRA nod and EU approval, Joanna Maitland Smith, executive director of scientific affairs at Merck U.K. (Merck Sharp & Dohme), told the conference.

There was a significant workload involved in securing the EAMS designation, with Maitland Smith noting she has a file of more than 3,000 emails relating to the process. It was hard dealing with the work at a time when corporate resources were focused on preparing the regulatory file and it required considerable coordination to ensure consistency between the marketing authorization application and the file being prepared for MHRA.

Her colleagues in the U.S. head office questioned whether EAMS offered any advantages, but Maitland Smith said she was able to persuade them that having a positive scientific opinion from MHRA would add credibility, and the involvement of NICE and NHS commissioners would reduce access timelines following EU marketing approval.

NOT ENOUGH TIME?

As well as being the first EAMS drug, Keytruda also is the product to have held the designation for longest. Others have hovered around two months, and in one case it was 21 days. But in another, the gap between EAMS designation and marketing approval was only 10 days – too short for the designation to be acted on.

Even so, more patients are getting access to unlicensed drugs than companies estimated in their EAMS submissions, said Malcolm Qualie, pharmacy lead at NHS Specialized Services, who has been involved in implementing EAMS. However, the short EAMS periods have created difficulties for clinicians. "They don't want to start talking to the patients and then EAMS ends," Qualie said.

Nick Crabb, project director, scientific affairs at NICE, noted the EAMS periods generally have been too short for real-world evidence generation, which is one of the objectives of the scheme. "There's not enough time from an NICE perspective," he said. The MHRA is prepared to consider products in phase II development. "So if companies engaged earlier, more patients would benefit and we would get more real-world evidence." Crabb said.

Steve Bates, chief executive of the BIA, is delighted to see the "delicate flower" of EAMS is growing, but is not convinced it can survive hard frosts. "Why it works is not just the process, but the attitude and commitment across the system," he explained.

It remains an issue that EAMS is not funded and companies must supply drugs free of charge. Other countries have similar access schemes that are funded. "If our early access scheme is not globally competitive, this is not good," said Bates. "This is about industrial strategy."

Source