Neurocrine Biosciences has announced that they received a second approvable letter from the FDA for their product indiplon for the treatment of insomnia.
According to the company release:
On May 15, 2006, the Company received an action letter from the FDA stating that indiplon 5 mg and 10 mg capsules were approvable (2006 Approvable Letter). The 2006 Approvable Letter requested that the company reanalyze data from certain preclinical and clinical studies to support approval of indiplon 5 mg and 10 mg capsules for sleep initiation and middle of the night dosing. The 2006 Approvable Letter also requested reexamination of the safety analyses. At the August 2006 end-of-review meeting where the 2006 Approvable Letter was discussed, the FDA requested that the resubmission include further analyses and modifications of analyses previously submitted to address questions raised by the FDA in the initial review. This reanalysis was completed and was resubmitted on June 12, 2007.
On December 12, 2007, we received an action letter from the FDA stating that indiplon 5mg and 10mg capsules are Approvable (2007 Approvable Letter). The 2007 Approvable Letter did not raise any of the issues previously raised by FDA in the 2006 Approvable Letter.
The requirements as spelled out in the 2007 Approvable Letter raised requirements as follows:
- An objective/subjective clinical trial in the elderly
- A safety study assessing the rates of adverse events occuring with indiplon when compared to a marketed product
- A preclinical study to evaluate indiplon administration during the third trimester of pregnancy
I am struck by the second requirement – that the company compare adverse events with an existing product. Perhaps that is common and has escaped my notice, but is it a new standard that new compounds have to demonstrate less risk than the status quo in order to gain approval? If so, the FDA should spell that out ahead of time, especially for small companies that have few products or are looking to get their first product to market.
Did the FDA ask for this initially and the company simply decided not to do it – or is the FDA moving the goal post on approval in the middle of the application? Granted, there may be studies that are required as a consequence of the studies that are submitted for consideration, but this requirement hardly seems like one of them. The FDA needs to make clear at the outset when these kinds of studies are going to be required. Otherwise, the approval process, while within the letter of the law, certainly falls outside of the spirit of PDUFA – to get drugs approved and to market more quickly.
This year, with an approvable letter rate that bears scrutiny and raises many questions about what FDA policy, has certainly put a dent in the whole point of PDUFA.