BNET: Have you asked the agency to provide an opportunity for a hearing on the question of whether there are actual grounds for denying approval of the application?
Rich Pascoe: When we meet with the FDA later in January we'll have additional insights into a potential path forward.
BNET: At that meeting - and this is just supposition - what alternative approval route for Silenor would be amenable to the FDA - without submitting outcomes data from new (time-consuming) trials?
RP: It would not be advisable to presume anything in advance of our meeting. We'll listen closely to their position and manage our course thereafter accordingly.
BNET: Does the FDA still harbor any safety concerns, in particular, the debated issue that Silenor may prolong cardiac QT interval, leading to potential adverse events like tachyarrhythmias and sudden death?
RP: In the first Complete Response Letter received on February 25th, the FDA noted that there were no adverse events observed in the clinical studies included in the NDA that would preclude approval, but asked the company to address the possibility that doxepin might prolong the cardiac QT interval.
The second Complete Response Letter received on December 7 didn't raise any new clinical safety issues. The NDA resubmission we filed last year had [included] results from completed Silenor trials that evaluated electrocardiogram effects. Conclusive evidence demonstrated that the drug had no effect on QT interval prolongation when administered at up to 6 mg, or under exaggerated exposure up to 50 mg.
BNET: Why, therefore, did the Response Letter request that the company submit a Risk Evaluation and Mitigation Strategy (REMS), including a medication guide to be submitted with the product - especially since Silenor is likely - if and when approved - to be a non-scheduled drug?
RP: The rationale behind the REMS is to assure the safe use of the drug, and this request should not necessarily be construed in a negative light. In fact, it is more common than not for the FDA to require manufacturers of sleep hypnotics to institute risk protocols.
BNET: Some analysts say your window of sales opportunity is closing, with patent expiry around 2013. Is that true?
RP: Silenor currently has issued patents that provide exclusivity through 2020. Additionally, generic intrusion is an unlikely threat: Silenor is manufactured as 3 mg and 6 mg tablets. Doxepin is currently available in a 10 mg capsule form - making interchangeability difficult.
BNET: The insomnia market is crowded. What features do you believe will be enough to convince physicians to switch from more established sleep hypnotics, which include Lunesta (eszopiclone), Ambien CR (and its generic zolpidem), and Restoril (and its generic temazepam)?
RP: Our market research revealed that 67 percent of all patients currently on an Rx insomnia therapy reported that they aren't satisfied with their current treatment [and] more than 56 million people self-medicate with OTC therapies primarily out of fear of the unwanted side effects associated with those Rx treatments (see figure above; click for a larger version).
We believe there is ample room for a new agent such as Silenor in the market, particularly one with a highly differentiated mechanism of action, a strong clinical efficacy profile, and a favorable safety and tolerability profile characterized by the its non-scheduled status, adverse events comparable to placebo, and a lack of GABA-ergic (gamma-amino butyric acid) related side effects commonly experienced by patients who take the marketed products.