When researchers discover a new drug, getting it from the idea stage in a lab to pharmacy shelves requires careful work, testing, and teamwork among scientists, doctors, and others.
One of the newest drugs for migraine, AXS-07 (Symbravo) received FDA approval on Jan. 31, 2025. AXS-07 is approved to treat acute migraine attacks.
Here’s how it was made, why it’s safe, and how it can help those living with migraine.
Step 1: Discovery and Development
AXS-07 is unique, as it’s a combination of two existing drugs: meloxicam (a nonsteroidal anti-inflammatory, or NSAID) and rizatriptan. Meloxicam was already FDA-approved for arthritis, and rizatriptan for migraine. This NSAID/triptan combination isn’t new. The FDA approved Treximet, which is a combination of naproxen sodium and sumatriptan, in 2008.
This newer combination combines two newer generations of both these drugs. Earlier anti-inflammatory medicines like naproxen typically block enzymes called COX1 and COX2, which are responsible for pain, inflammation, fever, and swelling. Meloxicam is not only more potent than earlier NSAIDs, it specifically blocks COX2 and not COX1.
“The reason you want a drug that blocks more specifically is that you get fewer side effects, primarily GI-related,” says Shivang Joshi, MD, MPH, RPh, director of headache medicine at Community Neuroscience Services in Westborough, Massachusetts, and an assistant professor of neurology at the University of Massachusetts.
Not only was naproxen not a COX2-specific medication, the triptan it’s combined with in Treximet, sumatriptan, is an older-generation triptan medication that is slightly less effective than the newer generations of triptans.
“The idea with AXS-07 was that you’d basically get a better drug combination when compared to the previous combination,” says Joshi.
But investigators also knew that it wasn’t just the drugs in the combination, it was how they were combined that would make a better drug. Treximet was a tablet that expanded in the stomach and delivered the medication slowly over time. With AXS-07, they developed an improved mechanism.
“It's a unique mosaic technology that not only allows for rapid absorption, but it also allows for a long-term release of the drug, too,” says Joshi. “Sometimes you want things that are getting to the system quickly, but also last a longer period of time. So that's the main difference between the previous generation of combination of NSAIDs or anti-inflammatory drugs with triptans.”
Step 2: Testing in the Lab
Many drugs start with testing in animals before human subjects try them. But typically, investigators can skip that part of the process when the molecules they’re testing have already been established, says Joshi.
“When you initially propose a new molecule, you start out with animal studies, science lab-based research studies, where we're trying to identify the most effective molecule,” says Joshi. “But in this scenario, you already have the molecule identified.”
In the case of AXS-07, this meant they could move on more quickly to what they can do to make the molecule work better. In the lab, scientists worked on how the drug could be best delivered into the body, and which molecules to combine to have the maximum effectiveness and safety.
The drug company (Axsome) developed a technology, called Molecular Solubility Enhanced Inclusion Complex (MoSEIC), that could deliver the drug this way.
Step 3: Testing in People
When it’s time to test a drug in people, investigators will do this through clinical trials in phases:
Phase I focuses mainly on safety. Researchers will recruit about 30 to 80 volunteers who take the drug and are monitored for side effects. This process takes a few months to a year. About 70% of drugs make it past this point in the process.
Phase II of the approval process mostly focuses on effectiveness, or how well the drug works to treat the condition. The pool of volunteers for this phase is larger and the trial is longer. Typically, it involves about 50 to 400 patient volunteers and runs for one to two years. As they look at the drug’s effectiveness, they also look at safety.
When they get a signal that the drug is safe and working well, they move to phase III. Only 33% of drugs make it past this step.
Phase III is the longest phase, lasting from one to four years and involving thousands of people. AXS-07’s approval came from three phase III trials: MOMENTUM, INTERCEPT, and MOVEMENT.
The MOMENTUM trial treated migraine of moderate and severe pain intensity, and recorded results from more than 21,000 migraine attacks combined. More people who took AXS-07 had pain relief and freedom from their most bothersome symptoms (nausea and sensitivity to light and sound) two hours after taking the drug than the people who took a placebo.
The INTERCEPT trial had similar results, but with mild migraine.
The MOVEMENT trial was long-term and open-label with 706 patients to test safety in people who have at least two migraines per month. Results showed 85% of patients remained free of rescue medication use through 24 hours and 83% through 48 hours.
Step 4: Checking by Experts
The drug approval process, which happens through the FDA’s Center for Drug Evaluation and Research (CDER) is rigorous and involved. Once a drug makes it to this stage, it’s been through lots of testing.
In 2021, results from two phase III trials for AXS-07 went on to the FDA approval process, but the FDA asked for more information related to the chemistry, drug-making, and controls for the drug.
This is called a resubmission and means either something was not clear enough to the FDA or they are giving the company some advice on what needs to be done, and then the company will resubmit either longer studies or bigger studies or specifically address FDA concerns.
Although the FDA didn’t request further clinical trials, when Axsome resubmitted the drug, they included results from another trial (MOMENTUM).
Step 5: Watching Over Time
The FDA requires a very rigorous process to assess the efficacy and safety and approve a drug. But even after approval, they continue to monitor it, a process called post-marketing surveillance.
“That's important because it looks out for any adverse effects that were not showing up in standard clinical trials,” says Joshi. “Because when you do a clinical trial, you have a limited population. But in the real world, you have patients that have other comorbid conditions, and other genetic makeup.”
In the post-marketing surveillance, says Joshi, all health providers who are involved in treating patients are required to report to the FDA if they notice any adverse effects. If something is severe enough, they will go back to the FDA. The FDA will make some amendments and changes to their FDA label.
The Bottom Line
Researchers, doctors, and other experts have tested and retested AXS-07 and have found it to be safe and effective. It’s a well-established process that’s there to help medicines be as helpful as they can be.
“This is not a new, invented molecule, or a new, invented mechanism,” says Joshi. “It's taking something that we’ve known about for many, many years and making it more effective. So that should give people who try it reassurance that it’s safe and effective.”
AXS-07 should be available for prescription in May 2025.
