EMA Spells Out New Expectations for Adaptive Pathways Applications

Regulatory News

The European Medicines Agency (EMA) has issued a new guidance to help companies applying to its adaptive pathways pilot.

Background

EMA launched its adaptive pathways pilot in 2014 to speed access to new medicines in areas of "high medical need" by leveraging existing approval pathways to support "early and progressive patient access" to new medicines.

Under the pilot, drugs would either be authorized conditionally or in a staggered fashion by narrow indication before using additional clinical and real-world data to support full authorization.

Pilot Applicants

While EMA has already accepted 19 proposals to its adaptive pathways pilot, the agency says it is still seeking applicants with "well-developed" proposals to take part in the pilot.

One participating company Bluebird Bio, said in May that it plans to seek conditional approval for its gene therapy LentiGlobin BB305 to treat beta-thalassemia major by demonstrating a reduction in transfusion need, then using additional clinical trials, "supportive long-term follow-up data and 'real-life' post-approval monitoring data" to supplement its authorization.

Similarly, Immunocore said in September it plans to seek conditional approval for its lead biologic IMCgp100 for the treatment of patients with metastatic uveal melanoma, a rare and fatal disease with few available treatment options. Conversion to full approval will be subject to the successful completion of a Phase II trial in uveal melanoma with long-term follow-up data.

And in August, a third participant Pluristem Therapeutics, said it's using EMA's guidance in the pilot to develop a cell-therapy product that targets a subgroup of patients with critical limb ischemia (CLI) before looking to expand to other patient subgroups.

New Guidance

In its guidance released earlier this month, the agency says that applicants must show that their drug development plan must meet three criteria before being considered for the adaptive pathways pilot.

First, companies must plan on either pursuing a staggered or conditional marketing authorization.

So far, EMA says that in many cases companies did not specify a proposed authorization route; however, some of the accepted proposals featured both a staggered and conditional authorization route. Of the 19 accepted proposals, 15 sought to expand the indication to a wider patient population, 11 (or more) sought conditional marketing authorization and 11 sought approval based on an early/surrogate endpoint.

Second, companies must plan to collect "real-life data to supplement clinical trial data."

This data could include information gathered from disease registries, natural history studies, compassionate use data and/or post-authorisation studies.

Third, companies must plan to involve patients and health technology assessment (HTA) bodies in their crafting their drug development plans.

EMA says that successful applicants had specific issues they sought to resolve with patient/HTA involvement, including whether proposed endpoints and post-approval studies are appropriate.

Additionally, sponsors must show that their product is suitable for the pilot project by demonstrating that traditional pathways or processes are not appropriate. Otherwise, EMA says companies should follow established procedures or pathways such as scientific advice, EMA-HTA parallel scientific advice or seek conditional marketing authorization.

EMA