NVD-201 - Sumatriptan Oral Spray (OS)
NVD-201 is NovaDel’s proprietary oral spray formulation of sumatriptan being developed for the treatment of migraine headaches. Sumatriptan is the active ingredient in GlaxoSmithKline’s Imitrex®/Imigran®, the leading prescription therapy for migraine headaches in the world, which is available in tablet, injectable and intranasal forms.

The potential benefit of NVD-201 is a fast onset of action at a lower dose compared to traditional sumatriptan tablets.

Clinical Studies

NovaDel has completed two clinical studies:

PHI-001 – Pilot Pharmacokinetic Study in Healthy Volunteers
This study was a four-arm, crossover pharmacokinetic study comparing 50 mg Imitrex® tablets to 20 mg and 30 mg of NVD-201 in 10 healthy male volunteers under fasting conditions.  The pharmacokinetic parameters of the 20 mg NVD-201 after a meal were also evaluated.  The study demonstrated a statistically significantly faster rate of absorption than Imitrex® tablets and up to a 50% increase in relative bioavailability of drug.  Importantly, the rate of drug absorption is believed to be predictive of the degree and speed of migraine relief.  Although Imitrex® nasal spray was not included in this clinical study, time to the first peak plasma concentration of sumatriptan was approximately 70% faster with the 20 mg NVD-201 than what has been reported in the literature for the same dose of the Imitrex® nasal spray.  In addition, the mean concentration level achieved during this critical first phase of absorption was approximately 30% greater for NVD-201 than what was observed in published studies of the nasal spray.

CLIN-001-IN – Pilot Efficacy Study in Migraneurs
This was a multi-center, active control, open-label, dose-ranging, efficacy and safety study.  Subjects received up to 5 treatments, comprising single doses of the following: Imigran® 50-mg tablets, NVD-201 20-mg, NVD-201 30-mg, Imigran® 100-mg tablets, and NVD-201 40-mg.  Their response to Imigran® 50-mg tablets determined whether they were eligible to receive the other four treatments.  Patients recorded the severity of each migraine attack on the same 4-point scale immediately before dosing and at 15, 30, 60, 90, 120, 240 minutes and 24 hours post-dosing.  Associated symptoms (nausea, vomiting, photophobia, and phonophobia) were also recorded immediately before dosing and at 30, 60, 90 and 120 minutes post-dosing.  All dosing was done on an outpatient basis and patients returned to the clinic between migraine attacks. 

In the primary analysis of efficacy, the percentage of patients responding to treatment at or before 60 minutes post-dosing, there was a statistically significant greater percentage of subjects receiving the 30- and 40-mg doses of NVD-201 with a reduction in headache pain compared to those receiving the 50-mg s Imigran® tablet (42% and 46%, respectively, vs 12%; P≤0.011), and was comparable to the percentage who responded to the higher (100 mg) dose of the tablet formulation (42%).   Significantly more patients had responded to all three doses of NVD-201 than to 50-mg Imigran® tablet by 90 minutes post-dosing (57% to 70.0% vs 32%; P≤0.028) and all three oral spray doses were comparable to the 100-mg tablet.  There were no treatment differences by 2 hours after dosing, when 68% to 77% of patients had responded irrespective of treatment.

Compared to 50-mg Imigran® tablet, at least one dose of NVD-201 also significantly increased percentage of patients who were pain free by 1 to 2 hours post-dosing, with the response ratio indicating significantly faster complete pain relief for the 40-mg dose, and significantly more patients had complete pain relief without use of rescue medication after receiving any dose of NVD-201.  In addition, after one or more doses of NVD-201, the percentage of patients who were asymptomatic was significantly increased, and the percentages who experienced nausea, photophobia, or phonophobia were significantly decreased.  NVD-201 was comparable to the 100-mg tablet on all the above measures.

Current Status

NovaDel plans to continue its clinical development efforts for NVD-201 with a definitive pharmacokinetic study in 2009.

About Migraine

According to the American Medical Association, an estimated 26 million people in the U.S. suffer from migraine headaches.  An estimated 150 million workdays, which translates into 1,200 million work hours, are reported lost due to the onset of migraine headaches, and cost employers an estimated $13 billion annually.  Sales of Imitrex are estimated to be approximately $1.0 billion, representing roughly half of the migraine market.  The U.S. patent exclusivity for Imitrex expires in February 2009