Migraine Treatments of the Month: Zavzpret Nasal Spray
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Ever since injectable sumatriptan was approved for use in the US, the holy grail of “rescue” medication for acute migraine headache of moderate to severe intensity has been a therapy which would offer injectable sumatriptan’s rapid headache relief…without the need for injection, without the bothersome side effects that may occur with sumatriptan, and without the concern that use of the drug might cause a vascular complication such as heart attack or stroke.
While many individuals with migraine respond quite well and consistently to acute treatment with one of the seven oral triptans currently available, an oral compound containing sumatriptan and naproxen sodium, ubrogepant (Ubrelvy), rimegepant (Nurtec) or lasmiditan (Reyvow), in none of the research studies which earned those drugs their FDA approval did any match the speed of injectable sumatriptan. As is hardly surprising: an orally administered medication has to make its way through the stomach (where the migraine itself may slow transit time), then into the small intestine, then into the arterial blood circulation and then - at last - to its therapeutic target…all the while evading proteins which reside in the stomach, intestine and liver and are dedicated to its deactivation.
To bypass this tricky gastrointestinal route without the need for self-injection directly into the vascular circulation, investigators naturally turned their attention to the intranasal portal as an alternative path to reach the bloodstream. Their efforts led to the development of nasal sprays for administering sumatriptan, zolmitriptan (Zomig), and a related molecule, dihydroergotamine (DHE: Migranal, Trudhesa). While the jury is still out on Trudhesa, only a relatively small proportion of the migraine population have found one of the other alternatives mentioned to be sufficiently superior to oral therapy to justify their use. Much the same has occurred with Onzetra, a formulation of sumatriptan which exists as a powder that one administers into the nasal cavity by exhaling into the device’s mouthpiece. As with Onzetra, a sumatriptan (Zecuity) transdermal patch intended to deliver the drug into the small blood vessels supplying the skin never caught fire with prescribing providers or the migraine population.
On March 10 the FDA approved the latest candidate for the holy grail referred to in the introductory paragraph: zavegepant (Zavzpret). Like oral Ubrelvy and Nurtec, Zavzpret is a gepant, but it is the firstgepant to be available in a nasal spray formulation. Two well-conducted clinical research studies involving a large number of migraine patients demonstrated the new drug and its delivery system to be safe, well tolerated and effective for the treatment of acute migraine headache of moderate to severe intensity. In terms of headache relief, Zavzpret was superior to placebo as early as 15 minutes following study drug administration, and for the primary study endpoint of freedom from headache at 2 hours the drug was similarly superior. The most common side effect, occurring in about 1/5th of patients administering Zavzpret, was distortion of taste, with nasal discomfort or nausea occurring much less frequently.
Could Zavzpret represent the long-sought holy grail for acute migraine treatment? Will it prove as effective - and as rapidly effective - as injectable sumatriptan for “rescue” from a migraineur’s most severe migraine headaches? For some…undoubtedly. For most…probably not. For those who are motivated to try all three options, Zavzpret nasal spray is likely to provide more rapid relief than an orally administered medication but a slower onset of therapeutic action than that achieved with injectable sumatriptan.
What Zavzpret can offer, however, is a very nice alternative for patients who prefer not to self-inject, in whom nausea precludes oral therapy, whose experience with injectable sumatriptan has been suboptimal or who are excluded from using a triptan consequent to vascular risk factors. And for a disorder as multifaceted as migraine, it’s always nice to have another option.
