HAMBURG – By late Wednesday afternoon, 18 drug developers filed applications for inclusion in the first batch of projects to benefit from a suite of regulatory supports under the EMA's priority medicines initiative, Prime, which aims to accelerate the development and approval of medicines with the potential to make significant clinical impact in areas of unmet medical need.

Eleven of the 18 were from small and medium-sized enterprises, and the therapeutic areas involved include Alzheimer's disease and antimicrobial resistance, two priority areas for the European Commission. (The EMA had to revise its original total of 19, as one application turned out to be submitted twice.)

The scheme already opened for business on March 7, with a closing date of April 6. According to the EMA's timetable, its Committee for Human Medicinal Products (CHMP) will finalize the selection of the first Prime-designated development projects on May 26. The eligibility assessment procedure takes 40 days, and the EMA is accepting new applications every month, with defined deadlines for submission.

The scheme, which has already undergone extensive consultation with stakeholders, is designed to introduce greater efficiency into the drug development process by providing developers with ongoing methodological guidance, starting from a kickoff meeting, and a rapporteur who will steer them through the process. (See BioWorld Today, Nov. 9, 2015.)

Small and medium-sized enterprises (SMEs) and academic developers can seek Prime designation on the basis of strong preclinical data and initial human safety data, whereas larger developers with more resources and development experience will need to generate clinical proof-of-concept data. The EMA is actively incentivizing SME and academic participation because, according to its own research, about one-third of therapeutic innovation comes from those sources.

The overarching motivation for the scheme is to accelerate drug development while avoiding failures because of inappropriate development strategies and flawed clinical trial design. "That is, at least in theory, preventable," Hans-Georg Eichler, senior medical officer at the EMA, told delegates during a Thursday morning briefing session at the DIA Europe 2016 meeting, which marked the formal launch of the program. Sparing patients the risks and burdens of participating in badly designed trials is an ethical imperative – first set out in the 1964 Helsinki Declaration, which Eichler translated as: "If you do a dumb study, it's unethical – don't do it."

Getting innovative therapies to patients in a timely manner is also important. For fatal conditions, such as metastatic cancer, every patient has a therapeutic window between initial diagnosis and death. Every year saved in the development process of a life-saving therapy could save a patient cohort that would otherwise die.

"We firmly stand behind this idea that early access is a benefit in itself," Eichler said. For that reason, he robustly defended the program against criticisms from non-governmental organizations and insurers that it could give rise to regulatory capture or to bias on the part of the rapporteurs – who will also be involved in the subsequent assessment of the program. "We flatly reject this notion that early engagement is a conflict of interest. We argue it's an ethical imperative, and we do this in the interests of patients," he said.

GETTING PAYERS TO 'PLAY BALL'

In itself, the scheme is not a guarantee that all patients in Europe will actually gain access to Prime-designated medicines, an issue that EMA officials were quick to recognize. There is a possibility that it is building a highway in the regulatory space but that drug developers will end up on a "gravel road" in the payer space, Eichler said.

So far, the buy-in from Europe's health technology assessment (HTA) agencies, which rule on the economic benefits of new drugs, has been "limited," Eichler said.

Their perception is that payers are expected to pay premium prices with less clinical data. "Whether the payer side will happen depends not only on the payers but also on industry," he said. "We can support that process – we cannot make it happen," he added.

CHMP Chairman Tomas Salmonson told delegates that HTA bodies and payers could find themselves in an awkward position if they fail to engage with newly approved therapies that offer a high clinical impact.

"The high [therapeutic] value will make them play ball, so to speak," he said. Conversely, being included in the Prime scheme does not confer any advantages in terms of gaining an approval. The assessment procedures are no different from those applied to existing approval pathways.

Comparisons will inevitably be drawn with the FDA's breakthrough therapy designation, which the agency introduced in 2012.

According to data compiled by the Friends of Cancer Research, the FDA had, by March 22, cumulatively granted 118 breakthrough designations, from which 39 approvals flowed, nine of which represented new indications for previously approved products. That marks one point of divergence from the Prime scheme. "At this stage, we're not opening up Prime for new indications," Salmonson said. Only novel therapies are eligible.

There are other differences. "They need to have clinical data – that's probably the biggest difference between us," Jordi Llinares, who heads the EMA's department of product development scientific support, told BioWorld Today. "We're very much focused on the accelerated assessment as an endpoint."

That approval pathway remains open to developers who opt to remain outside of the Prime scheme, but it will also represent the most likely route for participants in Prime. The scheme does not lock developers into a single trajectory, however, and if another pathway, such as conditional approval, turns out to be more appropriate for a particular program, it can be followed.

Not all of the questions surrounding the Prime scheme have been settled as yet. Salmonson noted that it has yet to decide whether the concept of "unmet medical need" will be defined in strictly European terms or whether it will take the global picture into account. That will probably be dealt with on a case-by-case basis, he said. The EMA has not issued formal targets about the number of designations it will confer.