New nasal spray drug awaits FDA approval

Migraine is a neurological condition different from a headache.

Migraine are severe and recurrent and can last anywhere from a few hours to several days.

Migraine symptoms can happen before, during, and after an episode. These can include:

“Migraine is characterized by debilitating attacks lasting four to 72 hours with multiple symptoms, including pulsating headaches of moderate to severe pain intensity that can be associated with nausea or vomiting, and/or sensitivity to sound (phonophobia) and sensitivity to light (photophobia),” Dr. Kathleen Mullin, associate medical director of the New England Institute for Neurology & Headache, explained to Medical News Today.

“While each person experiences migraine differently, the impact almost always disrupts their everyday life and the lives of those around them,” she added. “That’s why it’s important to have medications that can help people with migraine.”

Migraine triggers are different for everyone and may include:

One main group of medications used to treat migraine are gepants.

Gepants work by blocking a specific protein called calcitonin gene-related peptide (CGRP) associated with inflammation and pain.

According to Dr. Medhat Mikhael, a pain management specialist and medical director of the non-operative program at the Spine Health Center at MemorialCare Orange Coast Medical Center in California, there are small c-fibers on the trigeminal nerve, which is one of the 12 pairs of nerves attaching to the brain.

“When there is a trigger that starts the migraine, these c-fibers release big amounts of this (CGRP) protein,” he told Medical News Today. “And that CGRP protein binds onto the receptors and becomes very active. These receptors are on cells like nerve cells, blood vessel cells, and mast cells. When the CGRP protein binds to the receptor, an inflammatory cascade starts. And this is why you get that severe throbbing and also get some sensitivity to light or sound. So when we use the CGRP inhibitors, we prevent that cascade of reaction from happening so we don’t get to the dilatation of the trigeminal artery.”

“I like to describe gepants as a medicine that has a very specific method to block pain signals to the brain by inactivating the chemical messenger CGRP,” Dr. Frederick A. Godley, president of the Association of Migraine Disorders, told Medical News Today. “If you think of pain like a light fixture and nerves are like electric cords that are needed to turn on the light, then gepants are like the small plastic protectors that cover a wall socket. If you cannot plug in the cord to a wall socket, a light cannot turn on.”

Zavegepant is the latest drug in the gepant medications family.

According to Mullin, zavegepant is an investigational CGRP migraine medication that is delivered via a nasal spray.

“It blocks CGRP receptors in the brain and restricts the activity of the CGRP, which is believed to be a cause of migraine,” she explained.

During the phase 2/3 clinical trial, researchers reported that study participants treated with zavegepant experienced statistically significant pain relief in as early as 15 minutes compared to people who received a placebo.

The participants given zavegepan also had freedom from pain and their most bothersome symptoms 2 hours after dosing.

Scientists also reported participants were able to return to normal function within 30 minutes.

Because zavegepant is delivered as a nasal spray, Mikhael said that helps the drug work quickly.

“A drug that is delivered through the nasal mucosa is rapidly absorbed into the bloodstream because of a thin mucosa and a rich blood supply, so you can deliver the drug and get it absorbed and into action very fast… (and are) not waiting for a pill to go through the digestive tract, get metabolized, absorb it, and then see an effect,” he explained. “Not saying that the pills will be ineffective — they are effective — but it’s not going to be as fast as getting into the bloodstream, like going through the nasal mucosa.”

Additionally, a nasally-administered medication provides an alternative to people with migraine experiencing nausea and/or vomiting.

“Most of the patients that have migraine, as the migraine starts becoming moderate to severe, they almost always (have) nausea,” Mikhael said. “Even if they don’t throw up, they have nausea. If you have somebody with a migraine and you say take a couple of these pills, they don’t want to take it because they feel (like) they (are) going to throw up. So not going through the GI (tract) is an added plus, particularly with a common associated symptom like nausea.”

With the U.S. FDA soon voting on whether to approve zavegepant, medical experts agreed there are still some questions to be answered about the new drug.

Godley stated he worried about the taste of the nasal spray and how that may impact patients.

“While rimegepant has a pleasant minty flavor, the leading patient complaint about zavegepant is the poor taste of this nasal spray,” he explained. “The adverse events of dysgeusia (abnormal taste) is about 15 percent and nasal discomfort of roughly 3 percent, which is more than five times higher than placebo. I will be warning my patients to lower their heads after spraying with the hope of minimizing the solution from reaching the throat.”

Mikhael added the most challenging part for clinicians when working with a new drug is health insurance coverage. He said it can be disappointing when telling patients about a new FDA-approved drug and finding out health insurance does not yet cover it or it has a much higher co-pay than they are used to paying.

“I know it’s challenging these days, but it’s important for us to know how’s the coverage if the FDA approves the drug because that’s very important,” he said.