EMA keeps adaptive approval pathway open after 2-year pilot project


The European Medicines Agency is to continue accepting applications for adaptive approval after wrapping up a two-year pilot of the concept. The EMA pitched the pathway as a way for drugmakers to bring products to market in restricted patient populations on the basis of limited data, before gathering more evidence to support wider use postauthorization.

That core concept remains in place now that the pilot project is over. The agency handled 62 applications during the pilot phase, 44 of which were dismissed before holding a face-to-face meeting with the candidate, and now has a clearer picture of the types of product that are suitable for the adaptive pathway. This has led to the creation of a guidance document to help drug developers craft filings that will result in them joining the 6 companies to be accepted into the second stage of the process.

In a bid to cut the amount of time it spends sorting the promising prospects from the also-rans, the EMA has stated clearly what is likely to get dismissed or accepted. The EMA is more willing to accept drugs in indications it sees as posing evidence-generation challenges, such as those involving Alzheimer’s, rare cancers and degenerative diseases. Similarly, the regulator will look more favorably on products for which there are “clear-cut, actionable endpoints for post-authorization decision making.”

To date, less than 10% of filings made to the EMA have come close enough to meeting these criteria for the regulator to advance them to stage two. Half of the accepted applications were from small to medium-sized businesses. Oncology and hematology accounted for two-thirds of the successes, with anti-infective and cardiovascular drugs picking up the other two spots. Having advanced the 6 drugs to the second stage of the adaptive pathway process, the EMA then trimmed the field further still.

“It was possible to reach an agreement on a progressive development plan only in those cases where reliable surrogate endpoints existed, where the population to be initially treated could be clearly identified and where there was trust that a reliable post authorization data collection plan could be put in place to record long-term endpoints,” the EMA wrote in its report into the pilot project. Bluebird bio’s ($BLUE) beta-thalassemia gene therapy LentiGlobin BB305 is known to have met these criteria.

For bluebird, the pathway could provide a way to generate real-world data on the long-term safety and efficacy of LentiGlobin BB305, setting it up to convince regulators and payers of the value of its gene therapy. Yet, with the vast majority of companies to date never making it as far as a face-to-face meeting, let alone agreeing on an adaptive development plan, it is questionable whether the pathway will ever become more than a niche option.

- read the EMA’s statement
- here’s the report (PDF)
- and the guidance (PDF)

Related Article:
Pluristem snags spot on EMA's nascent fast-track scheme