W-19: Expanded Access Programs (EAP): A Look at 2015-2016 Orphan Designated New Molecular Entities
Medical Affairs Fellow
Alnylam Pharmaceuticals, Inc. United States
To compare timelines and geographies of sponsor-run Expanded Access Programs (EAP) for recently approved orphan designated new molecular entities (NME) in relation to the pivotal trials and FDA approval dates.
The 2015 and 2016 FDA Novel Drugs Summaries were used to identify orphan designated NME; diagnostic and imaging agents were excluded. Clinicaltrials.gov and Drugs@FDA websites were used for pivotal trial and EAP information. Individual patient and non-sponsor run EAP were excluded.
A total of 67 NMEs were approved by the FDA in 2015 and 2016; of these, 45% (30/67) were approved with an orphan drug designation. One-third (33%, 10/30) of the orphan designated therapies had a sponsor-run EAP. Among the 10 therapies with EAP, 60% (6/10) were approved for oncology indications while 40% (4/10) were non-oncology therapies.
The most frequently noted sequence of events, occurring in 50% (5/10) of all therapies reviewed, was completion of at least one pivotal trial, initiation of EAP, followed by NDA/BLA submission. This sequence of events was more typical in oncology therapies (67%) than non-oncology therapies (25%). The sequence of NDA/BLA submission posting followed by EAP initiation was seen in 30% of therapies: 17% (1/6) of oncology therapies and 50% (2/4) of non-oncology. Among those that initiated an EAP prior to NDA/BLA submission, only 1 oncology therapy utilized both safety and efficacy data from the EAP as part of their data package for approval.
Among the EAP reviewed, a majority of enrolling sites were within the US for both the oncology and non-oncology therapies. Non-oncology EAP took place in more European countries than oncology EAP. Thirty-three percent of oncology therapies and 25% of non-oncology therapies opened sites for the EAP in a country that was not included in the pivotal trials. All of the other EAP (70%, 7/10) took place in the same countries as the pivotal trials.
Expanded Access Programs provide an opportunity for eligible patient access to investigational therapies prior to their marketing approval. While the majority of oncology EAP were posted prior to FDA filling, the non-oncology EAP did not follow a similar pattern. More oncology EAP sites were opened in countries that did not have sites in the pivotal trials than non-oncology therapies. Oncology and non-oncology therapies differed in their timelines of starting an EAP and in the geographic locations they were available. These trends can be considered by sponsors looking to understand when and where to implement an EAP for an orphan designated NME.