Last week I gave a snapshot of the formal process undertaken by the European Medicines Agency (EMA) to review a Marketing Authorisation Application (MAA) dossier under the Centralised Procedure. While this provides some context, looking at historical review timelines provides some sense of how long a future application may take. This is far from an exact science, but given the queries we have received of late on approvals timelines, I felt it appropriate to provide some internal perspective.
The EMA’s timelines are confidential, with only set time points at which companies are allowed to publish information (CHMP meetings in particular). Once a drug has been approved by the EMA, however, the Agency issues a summary of the entire review process, known as an EPAR, or European Public Assessment Report. This document outlines the timeframes required by the EMA to perform the review, along with the names of the co-rapporteurs and a summary of the product in some depth, much of which likely reflects the dossier submitted, albeit in an abbreviated version. (The EPARs are published online by the EMA and are free to download.)
At present, there are 65 approved orphan drugs represented with EPARs on the EMA’s website. These exclude at least one recent approval (Novartis’ Jakavi), but represent approvals dating back to 2001. The numbers tell an interesting story.
For all orphan approvals, the mean procedure time from submission of an application to European Commission ratification was 502 days, with a median time of 471 days. For those drugs approved from 2007 until today (36 drugs), those numbers drop to 500 and 460. If one excludes those orphan drugs which have had negative CHMP opinions issued and then been approved on appeal (Gilead’s Cayston, Epicept’s Ceplene and Pharmaxis’ Bronchitol), the 2007 until today mean is 481 days and the median is 453 days.
This seems like quite a process, but probably of greater relevance is the time taken from the EMA’s acceptance of a MAA dossier until the announcement of a CHMP opinion; which is widely considered the EMA’s review process. Here, the average review time for all 65 EPARs is 387 days, with a median of 358 days. These numbers don’t change significantly for the 2007-present period, unless you exclude the three negative opinions, producing a mean of 377 days and a median of 365 days.
The fastest review was Novartis’ Glivec (Gleevec in the US), which took just 121 days from dossier acceptance to CHMP opinion, with the 20 fastest reviews of orphan drugs taking, on average, 248 days from dossier acceptance to CHMP opinion.
The slowest review was Pharmaxis’ Bronchitol, which took 841 days (after suffering a negative opinion setback), with the 20 slowest reviews taking, on average, 555 days. (Bronchitol was, however, not the slowest drug to go from submission to EC approval; that was seen by Shire’s Xagrid, approved in 966 days in 2004 under Exceptional circumstances, and taking 110 days from CHMP opinion-EC ratification).
In reality, the figures can tell only part of the story. Each orphan drug’s path to market is unique, relying on years of work by dedicated teams to ensure a product can be proven safe and effective as a treatment for patients who have often had little or no previous therapy. Despite this, I will try to add context to the EPAR data after it has been released by the EMA and will update some of the numbers above, should anything relevant arise. Looking further, I also hope to be able to publish relevant news on the EMA’s review of Clinuvel’s SCENESSE® (afamelanotide) as and when the Agency allows us.
‘Map of New Europe’ posted to Flickr.com by Cea. <http://www.flickr.com/photos/centralasian/6713923007/> (See site for license details).