New dosage form for migraine treatment
In January, 2016, FDA approved Onzetra Xsail (Avanir Pharmaceuticals Inc.)— a fast-acting, low-dose sumatriptan dry powder formulation for the acute treatment of migraine with or without aura in adults.
Although various sumatriptan formulations exist, each has limitations. Oral delivery is common, but has inconsistent effectiveness due to delayed absorption and requires a higher dose to overcome poor bioavailability. Nasal-spray delivery is associated with variable drug loss from drip-outs and accumulation at the nasal cavity floor, which is ultimately swallowed and subjected to challenges similar to those of oral delivery. Subcutaneous delivery is most effective. However, it is inconvenient, painful, and associated with high frequency of local and systemic side effects. Onzetra Xsail utilizes a novel closed-palate, breath-powered intranasal drug delivery system to overcome these limitations.
Sumatriptan is a 5HT1B/1D receptor agonist. For migraine relief, it acts to constrict the intracranial blood vessels and inhibit pro-inflammatory neuropeptide release.
FDA approval was based on a double-blinded, multi-centered, placebo-controlled, parallel-group study. Males and females, 18-65 years of age, diagnosed with migraine who reported 1 to 8 migraine headaches per month in the past 12 months prior to screening were included in the study. Participants received Onzetra Xsail, 22mg or placebo, to treat moderate/severe migraine episodes. The primary endpoint was reduction in headache intensity 2 hours after treatment. Secondary endpoints included headache relief at other time points, pain freedom, relief of migraine-associated symptoms (nausea/vomiting, phonophobia, photophobia), reduction in clinical disability scale score, rescue medication use, and maintenance of headache response.
Statistically significant reduction in headache intensity 2 hours post-treatment was observed in the Onzetra group (67.6% v. 45.2%, p=0.002). Average time to meaningful pain relief was 47 minutes for participants receiving Onzentra Xsail; 19.4% of study participants experienced relief in as few as 15 minutes.
Significant differences favoring Onzentra Xsail regarding maintenance of relief at 24 and 48 hours post-administration were demonstrated. Use of rescue medication was significantly lower in Onzetra group (37.0% v. 51.9%, p=0.02 ).
Onzetra Xsail is used only if a diagnosis of migraine has been established, and is not indicated for migraine prevention or for hemiplegic or basilar migraine. The most common adverse effects reported were local (abnormal product taste, nasal discomfort, and rhinitis) and generally resolved within 2 hours of administration. Most adverse effects were mild/moderate in intensity.