Migraine Treatment Developments On the Horizon in 2021

Migraine Treatment Developments On the Horizon in 2021

People with migraine disease have seen more positive developments in the last three years than we’ve seen in decades, with new classes of preventive and acute treatments, new devices, increased public awareness and support, and more research and development. Although many people with migraine have experienced greater relief through these breakthroughs, many more are still waiting for treatments that work for them.


The good news is that more promising advancements are on the horizon, including new medications, new delivery systems to make existing medications more effective, and devices that don’t use medication at all. Here’s a look at some of the developments on the horizon in 2021:




Gepants: Gepants, like the CGRP monoclonal antibodies used as preventive medications, block the action of the CGRP protein that plays a big role in the migraine process. Unlike the preventives, however, these acute treatments are small molecules that can block CGRP receptors without requiring injection. Because they do not constrict blood vessels, they may help people whose cardiac or vascular risks prevent them from using triptans, which do constrict blood vessels.¹ Gepants are currently only FDA-approved as acute treatment, however, they are now being studied for use as preventive treatments, potentially helping those who haven’t found the CGRP monoclonal antibodies effective or who prefer oral formulations over injections.


One of the gepants we are watching is Biohaven’s zavegepant. The company’s first acute oral migraine medication, rimegepant (brand name Nurtec ODT) has been effective for many patients in its first year on the market. Under study in nasal spray and oral formulations, zavegepant performed well as an acute migraine medication in a Phase 2/3 clinical trial with significant benefit demonstrated on freedom from pain and most bothersome symptoms at two hours after dosing. It also produced rapid onset with pain relief at 15 minutes (10 and 20mg) and  return to normal function as early as 30 minutes (20mg). ²

The surprising development here is zavegepant’s possible benefit for indications other than migraine—including the COVID-19 virus.  In April 2020, the FDA granted Biohaven permission to begin a Phase 2 clinical study of zavegepant’s potential use in mitigating an excessive immune response, which in some cases can be fatal in COVID-19.³ Biohaven also announced last November a collaboration with Weill Cornell Medicine to initiate a proof of concept trial with CGRP receptor antagonists in plaque psoriasis.


Psychedelics: Although psychedelic substances are currently prohibited in the US, researchers and advocates believe that they may be effective treatments for a number of neurological conditions, including migraine disease and cluster headache disease. Researchers who want to study their use have to clear substantial legal hurdles to do so, but in this Spotlight on Migraine podcast, Dr. Franklin King from Massachusetts General Hospital’s new Center for the Neuroscience of Psychedelics explains the science behind their potential benefits.4


While we don’t expect to see psychedelic-based treatments on the market in 2021, the growing interest in therapeutic uses may improve the legal and cultural landscape for more substantial clinical study.


Delivery systems


Several companies are working on new delivery systems for existing medications, a concept that could help millions of people with migraine disease and other conditions. 


Microneedle patch: Although the Qtrypta patch from Zosano Pharma needs more study before it gets FDA approval,the concept could open the door to making existing acute medications more effective for people with a common migraine symptom.


As many as half of the people who get migraine attacks experience nausea or vomiting. Even people who don’t report or notice distressing nausea or vomiting may experience gastroparesis, or a slowing of the stomach’s usual emptying process. These people may not be absorbing their acute medications quickly or fully, which means they’re getting inconsistent or incomplete relief. Typical alternatives for acute medications include injections and suppositories—not the most popular options among patients.


The Qtrypta patch contains tiny microneedles coated with zolmitriptan (brand name Zomig), an acute medication that’s been available for about 20 years. The microneedles deliver the medication into the top two layers of a patient’s skin,where it gets absorbed into the bloodstream without going near the digestive system. If the patch can deliver effective medication quickly and efficiently without falling into that digestive trap, it might give people with nausea, vomiting, or gastroparesis more effective and tolerable results. 

In late 2020, the FDA noted inconsistent blood serum levels of zolmitriptan in the initial clinical studies for Qtrypta and has asked Zosano Pharma to conduct further studies and product adjustments. 


Medication buffer: Axsome Therapeutics has developed a new acute therapy7 using two medications already in wide use. This therapy, now called AXS-07, combines a non-steroidal anti-inflammatory medication called meloxicam with rizatriptan, an acute medication in the triptan class.  

The company has developed another way to deal with the absorption issues in acute medications. 

Its proprietary “Molecular Solubility Enhanced Inclusion Complex” or MoSEICtm, changes the solubility and pH of the therapeutic ingredients of AXS-07. If MoSEIC can make the new therapy easier for the body to absorb more quickly and completely, patients who get inconsistent relief from acute treatments could benefit.8 


Deep nasal spray: Another intriguing development in the delivery system area is a deep nasal spray technology from Impel NeuroPharma. If you’ve ever used a nasal spray for sinus symptoms, the medication reached only the lower part of your sinus cavities, probably leaving a bad taste in your mouth from the postnasal drip. Researchers at Impel have developed a unique nasal spray delivery technology, called “POD” (Precision Olfactory Delivery). It propels medication into the upper sinus cavities, where tissues are rich in blood vessels and can absorb medication quickly and easily (and without the postnasal drip and bad taste). The tip of the device doesn’t go any farther into your nostril than other nasal spray devices; it simply deposits the medication much further up in the nasal space.  


Impel’s first step into migraine treatment combines this new technology with DHE (Dihydroergotamine), which has been used for acute migraine treatment since the 1940s. Although DHE has been a useful acute treatment for many people, the only ways to use it are via injection (either intramuscular or in an IV), requiring a visit to urgent care or the ED, or in a traditional nasal spray. Recently, the FDA accepted Impel’s New Drug Application and is scheduled to make a decision on whether to approve the treatment by September 6, 2021.9


If approved, Impel’s POD device could give people with migraine disease another effective tool for acute treatments that won’t require visits to urgent care or an emergency department.



Nerivio: The Nerivio neuromodulation device from Theranica is now approved for acute treatment of migraine attacks in people aged 12 and older with episodic and chronic migraine disease.10


Nerivio is an armband controlled by a mobile phone app (available for iPhone and Android). The armband contains a refillable neuromodulator that stimulates nerves in the upper arm, sending signals up the nerve pathways to the part of the brain that generates the pain of a migraine attack.11 The incoming signals from Nerivio can make that generator reduce the migraine attack signals it sends out, or even stop the migraine attack signals completely.


Nocira: Another device under investigation targets nerve clusters in the ear for neuromodulation. The Nocira device uses gentle puffs of air delivered through earbud-like pods to make subtle changes in pressure in the outer ear. That area contains a unique concentration of nerves thought to play roles in migraine pathophysiology–the vagus, trigeminal, facial, and glossopharyngeal nerves. Nocira’s preliminary tests using this “automated variable pulse insufflation” therapy, or AVPI, have shown significant relief for both episodic and chronic migraine patients. Nocira’s co-founder, Dr. David George, discusses the device in this episode of Spotlight on Migraine.12


More promising news


One of the most promising developments in migraine treatment in 2020 was a consequence of the pandemic: the expansion of telemedicine. In March 2020, the U.S. Department of Health and Human Services temporarily eased some of the regulations that limited the use of telemedicine.13 Clinicians and patients have been able to use phone calls and videoconferencing in ways that had been prohibited or limited by privacy and billing concerns. If telemedicine can become a permanent feature of the US medical industry, patients and clinicians alike have reason to hope for better results, more collaboration, and fewer obstacles.


2021 might bring us more breakthroughs and challenges we can’t predict right now, but we have every reason to hope that more people with migraine disease will have better, more pain-free days ahead. 










[9] Impel NDA Filing Acceptance Press Release, 1/20/21





Looking for more articles and information like this?



Lisa had migraine attacks for most of her adult life before being diagnosed with migraine disease. A communications strategist, writer, and former radio announcer, she lives in the Boston area, where she advocates for her fellow migraine patients every chance she gets.

Recent Posts

Recent Podcasts

Newsletter Signup