Avanir Pharmaceuticals, announced that COMPASS, its Phase IIIb clinical trial comparing the efficacy and safety of the investigational product AVP-825 22mg to sumatriptan 100mg tablets for the treatment of acute migraines in adults, met the primary efficacy endpoint. AVP-825 is an investigational drug-device combination product consisting of low-dose sumatriptan powder delivered intranasally utilizing a novel Breath Powered delivery technology. In March 2014, the US Food and Drug Administration (US FDA) accepted the New Drug Application (NDA) of AVP-825 and the Prescription Drug User Fee Act (PDUFA) V goal date is November 26, 2014.

The COMPASS study met the primary endpoint for the sum of pain intensity difference at 30 minutes post dose (SPID30), showing that migraine sufferers achieved greater pain relief within 30 minutes of treatment with 22 mg of the investigational product AVP-825 compared with 100 mg sumatriptan tablet (p<0.0001). In addition, AVP-825 treated migraine sufferers achieved pain freedom in a greater proportion of migraine attacks at 15, 30, 45, 60 and 90 minutes post dose compared with those treated with sumatriptan tablet (p<0.05). In these topline data, several additional secondary endpoints relating to pain relief were also met.

The overall safety profile of AVP-825, an investigational product, was consistent with that observed in previous trials, with less than 2 per cent of subjects experiencing an adverse event leading to treatment discontinuation. There were no serious adverse events in the study. Nasal discomfort and abnormal product taste were more common with AVP-825 administration; these adverse events were deemed mild in nearly 90 per cent of cases.  

Avanir plans to review the detailed data from the COMPASS study and present the full results at an upcoming medical meeting.

"There are millions of Americans suffering from migraine who are dissatisfied with their current treatment options," said Roger K. Cady, MD, Director of the Headache Care Centre and associate executive chairman of the National Headache Foundation. "By combining an innovative, targeted intranasal delivery system with sumatriptan, the most widely prescribed migraine medication, AVP-825 has the potential to provide migraine sufferers with an option that will address their needs for a fast-acting treatment that is well tolerated."

"AVP-825 was designed to deliver sumatriptan powder deep into the nasal cavity where is can be readily and efficiently absorbed," said Joao Siffert, MD, chief medical officer of Avanir. "These data show that AVP-825, an investigational product, can efficiently deliver sumatriptan and confers faster migraine headache relief at a lower dose than the most commonly utilized sumatriptan tablets."

The Compass study is a multicentre, randomised, double-blind, double-dummy crossover study in which migraine sufferers were treated with either 22 mg of the investigational drug-device combination product AVP-825 and placebo tablet or Breath Powered device-delivered placebo and 100 mg sumatriptan tablets. Study participants were instructed to treat up 5 migraine attacks in each 12-week treatment period. Migraine headache and presence of migraine associated symptoms of phonophobia (sensitivity to sound), photophobia (sensitivity to light) and nausea/vomiting were assessed immediately before dosing and at 10, 15, 30, 45, 60, 90 120 minutes and at 24 and 48 hours after administration. 275 participants and 1531 migraines were assessed during the study.

AVP-825 is an investigational drug-device combination product consisting of low-dose sumatriptan powder (22mg) delivered intranasally utilizing a novel Breath Powered delivery technology. If approved, AVP-825 would be the first and only fast-acting, dry-powder intranasal form of sumatriptan for the treatment of migraine. AVP-825 is an investigational drug-device combination product not approved by the FDA. In the phase III (TARGET) clinical trial the most common AEs (incidence >5%) reported for AVP-825 were product taste (22%), nasal discomfort (13%), and rhinitis (6%); local AEs were almost exclusively mild to moderate in severity and transient. Sumatriptan is contraindicated for certain patients, including those with a history of coronary artery disease (CAD) or coronary vasospasm.

The Breath Powered delivery technology is activated by user's breath to propel medications deep into the nasal cavity where absorption is more efficient and consistent than through most other routes. A user exhales into the device, automatically closing the soft palate and sealing off the nasal cavity completely. Through a sealing nosepiece placed into the nostril, the exhaled breath carries medication from the device directly into one side of the nose. Narrow nasal passages are gently expanded and medication is dispersed deep into the nasal cavity reaching areas where it can be rapidly absorbed. As the medication is delivered, the air flows around to the opposite side of the nasal cavity and exits through the other nostril. Closure of the soft palate helps prevent swallowing or inhalation of sumatriptan powder into the lungs.