The European Medicines Agency (EMA) has announced that it will be launching what it's billing as an "adaptive licensing pilot project," an initiative intended to grant earlier access to medicines meant to treat unmet needs.
Unlike the US' accelerated approval pathway, which grants a tentative but wide-ranging approval to a product based on interim data, EMA's adaptive licensing framework calls for the authorization of medicines for restricted (i.e. niche) patient populations followed by "iterative phases" of approval.
Earlier approvals would support subsequent (i.e. broader) approvals by allowing sponsors to collect real-world use data, EMA postulated.
"With the adaptive licensing pilot project we intend to explore with real medicines in development a progressive licensing approach that would allow timely access for patients to new medicines that address serious conditions with unmet medical needs," explains Hans-Georg Eichler, senior medical officer at EMA, in a statement. "The approach seeks to maximize the positive impact of new medicines on public health by balancing timely access for patients with the need to provide adequate evolving information on their benefits and risks."
A similar framework was launched in March 2014 by the UK's Medicines and Healthcare Products Regulatory Agency (MHRA).
Pilot Program
EMA's statement goes on to explain that the pilot program will be wide-ranging, including "as many programmes as necessary … to gather sufficient knowledge and experience, address a range of technical and scientific questions and further refines how the adaptive licensing pathway should be designed for different types of products and indications."
An accompanying document meant to guide adaptive licensing proposals calls for companies to answer eight main questions:
- Does the drug hold sufficient promise to address an unmet need?
- What evidence would support a positive benefit-risk in a defined (sub-) population at the time of initial licensing?
- What is the risk of failing to identify an important adverse effect based on early phase clinical trial data?
- What assurance of commitment from sponsor will there be to conduct further studies after the initial marketing authorization?
- What is the feasibility of any required follow-on RCTs after initial Marketing Authorization and what possibility to draw inferences from observational (non-RCT) data that are sufficiently reliable to support decision-making for regulators, payers and prescribers?
- What is the level of confidence that the observational part of adaptive licensing can be implemented (adequate infrastructure for registry or e-health records)?
- What is the likelihood that other decision-makers (HTA bodies/payers, healthcare professionals, patients) will be willing to contribute to discussions of the pilot?
- What is the level of confidence that prescriber behavior will be as anticipated? (risk of large share of off-label use, can this be mitigated by collaboration with payers?)
Companies wishing to participate in the pilot program are also asked to "outline a vision" of how payors, regulators and other stakeholders would work together throughout the product lifecycle.
The pilot program will only involve "live assets"-medicines in development-due to EMA's desire to better refine the adaptive licensing process.
All discussions between industry, regulators, payors and other stakeholders would take place in a "Safe harbor" environment, EMA said. Those discussions would have no bearing on future scientific advice, protocol assistance or marketing authorization application (MAA) meetings or documents.
Potential Hurdles
But for the program to work, EMA said it will need broad buy-in from a number of stakeholders, not all of whom may be eager to support adaptive licenses.
For example, a drug approved by EMA on a limited basis would still need to be paid for, either by patients, companies or government payors who often want evidence of the drug's value before agreeing to reimburse for a drug. Failure to obtain buy-in from payors might result in drugs that are technically available to patients, but actually not.
In the UK, MHRA has proposed making companies pay for early-access programs, conceptualizing them more as clinical trials. EMA made no note if similar discussions are under way on an EU-wide level.
EMA Statement
Nature Article on the Program