Allergan's NDA for Migraine Med With Novel Mechanism of Action Accepted by FDA

Migraines are a debilitating neurological disorder that can negatively impact the quality of life of those who suffer from them. Allergan, which has been a leader in the migraine space, hopes to have a new treatment available for patients using a new mechanism of action for acute treatment of migraine.

This week the U.S. Food and Drug Administration (FDA) accepted Allergan’s New Drug Application for ubrogepant, an oral CGRP (calcitonin gene-related peptide) receptor antagonist for the acute treatment of migraine. The NDA filing is based on four clinical studies that showed the efficacy, safety and tolerability of ubrogepant in a broad range of patients, including two Phase III trials. The studies showed that ubrogepant was well-tolerated in patients, even those who had an insufficient response to a triptan, which are the major treatments currently on the market, or those patients in whom triptans were contraindicated, Allergan said. The FDA has set a PDUFA date for the fourth quarter of this year.

For Allergan, the acceptance of the NDA has been highly-anticipated. Ubrogepant, if approved, will become a complementary treatment to the company’s migraine backbone of its blockbuster neurotoxin Botox, which is widely used to treat chronic migraines. Ubrogepant may not be the only migraine treatment the FDA will examine. The company also has a late-stage asset called atogepant, also an orally-administered investigational CGRP receptor antagonist, in development for migraine prevention.

Last year, atogepant met primary endpoints across all doses and dose regimens in a Phase IIb/III trial. Allergan said atogepant showed a statistically significant reduction in monthly migraine days.

Jessica Ailani, associate professor of neurology at MedStar's Georgetown University Hospital and director of the MedStar Georgetown Headache Center, said potential approval of ubrogepant will provide a new option for patients who are really suffering from migraine headaches. While migraines impact about 12 percent of the population in the United States, including children, Ailani said it remains an undertreated disease. About four million of those patients suffer from chronic migraines, meaning they are dealing with 15 migraines each month. Many patients are forced to additional treatment options from their physicians due to the difficulty of finding adequate relief. Severe migraine headaches have a negative impact on quality of life. People who are afflicted with these types of migraines typically remain in bed with the lights out. Even minor movement can be painful, Ailani said. Nausea and vomiting also become a factor and the effects can last for several days, she added.

“When we think about migraine, it’s a life-long disease. The lights bother you, the noise bothers you. The attacks happen at random. There’s no predictability for when they might occur. You can’t take care of yourself when this happens. You can’t cook for yourself, you can’t shower,” Ailani said.

But, if ubrogepant is approved, Ailani said it will be a new option for patients.

“Ubrogepant will be used across the entire spectrum of the disease (from episodic to chronic) helping patients achieve relief in the moments when they most demand it,” Ailani told BioSpace.

Joel Trugman, director of clinical development at Allergan, also told BioSpace that migraine headaches are really “a fascinating and complicated neurological disorder.”

In order to better understand what migraine patients go through when dealing with migraines, Allergan unveiled the “Frame of Mind” campaign. That campaign, launched in 2017, asked migraine sufferers to submit artwork to reflect what they’re going through when they have migraines.

Two years ago, BioSpace spoke with David Nicholson, Allergan’s head of research and development about the company’s migraine treatment platform. At the time he was touting the anti-CGRP research being conducted by Allergan. He said the oral CGRP treatments will complement the use of Botox for chronic migraine pain, particularly since the CGRP treatments are being developed as front-line treatments and Botox is used when many other treatments have proven ineffective.

If approved, Ubrogepant won’t be the first CGRP-based treatment on the market for migraine. Last year, the FDA approved three CGRP antagonists that are monoclonal antibodies administered to patients once per month. However, Ubrogepant will be the first oral treatment available in this class of drugs, Allergan said.