Definition of terms

The roller coaster of Duchenne has been in high gear this week with BioMarin’s announcement to halt trials and one day later, Acceleron’s press release about receiving Fast Track Status. I don’t know about you, but in a certain way, it sounds like Fast Track Status should be a high speed train, capable of 220 mph. The reality is that the Fast Track Status train is the same train, with better fuel (expedited review) and more tech support (FDA interaction).

I am pretty sure, everyone may have a different definition of Fast Track Status and thought maybe it would help to clarify what this means in reality.

In 1983, Congress passed the Orphan Drug Act.

Orphan Status:

• Drug (or biologic) for an orphan indication.
• Definition of rare disease– affects less than 200,000 people in the US
• High unmet medical need
• 7 years of market exclusivity
• Tax credit of up to 50% for qualified expenses for research support to support approval of the Orphan drug
• Exemption from several kinds of user fees
• Guidance from FDA staff to sponsors

The Division of Orphan Products is responsible for:

1. granting Orphan Status
2. is able to provide small grants for sponsors (based on application/review)

FDA

Fast Track Status – the purpose of Fast Track Status (accelerated approval and priority review) is to speed reviews and provide more extensive guidance to sponsors about the nature of the evidence that will be required in order to support approval.

• Includes a ‘rolling review’ by FDA, where companies submit modules of an NDA (new drug application) for a rolling review which allows more frequent consultation and dialogue with FDA on issues related to the application.
• Fast Track may include ‘accelerated approval’ which allows the use of surrogate (secondary) endpoints likely to predict clinical benefit. The FDA would likely require post-approval studies in order to collect additional evidence about safety and benefit.
• Fast Track applications may also qualify for ‘priority review’ which means FDA sets a goal of completing reviews within 6 months compared to the standard process of 10 months.

There is one more mechanism you might hear about to facilitate review – Special Protocol Assessment – which allows the FDA to provide expedited assessment of the adequacy or appropriateness of specific clinical trial protocols and to reach an agreement with sponsors about the design and size of a certain trial to support efficacy (benefit) claims. Normally, this is ONLY available at the end of a Phase II trial.

Bottom line: Acceleron has not gotten approval to start the trials in the US yet…Fast Track Status does not mean IND Approval.

This is all very difficult to take in and most of the time, seems pretty confusing. Often patients/families see the designation of Fast Track as some sort of vehicle that may deliver the drug quicker. In essence, because of the expedited review, guidance from FDA is intended for that purpose. But for those of us watching and waiting, heart in hand, it does not answer the ‘when’ question. It is strictly related to the FDA process.