A Depression Drug from Axsome Therapeutics Aimed to Get Started Quickly Now Long-Awaited agree One year after the FDA-determined target date. The regulatory nod announced Friday makes the product the first new oral drug in decades to address a new target for depression.
The drug, which is under development under the codename AXS-05, will be marketed under the Auvelity brand. New York-based Axsome plans to launch a twice-daily pill in the fourth quarter.
With the regulatory approval, Auvelity will join a depression drug market filled with older products, many of which take a long time to kick in and can have serious side effects. Many of these drugs work by targeting monoamine oxidase (MAO), blocking the enzyme’s ability to remove key neurotransmitters from the brain. MAO inhibitor drugs are widely used, but a large number of patients do not respond to them, and for those who do, effects can take six weeks or more to start.
Auvelity may be a new drug, but its two main ingredients are old ones. The product pairs bupropion (the active ingredient in the old GlaxoSmithKline antidepressant and smoking cessation drug Wellbutrin) with dextromethorphan (the ingredient in many cough suppressants). Dextromethorphan crosses the blood-brain barrier and targets the part of the brain that causes coughing. Auvelity uses dextromethorphan to block NMDA receptors, which the company says makes it the first new oral depression drug to work by addressing targets other than MAO in more than 60 years. The bupropion portion of this drug increases the level of dextromethorphan in the blood. Axsome combines two active ingredients with proprietary technology that modulates the delivery of each compound.
On a conference call Friday to discuss the approval, a financial analyst asked if doctors could bypass Auvelity by prescribing its two generic ingredients together. CEO Herriot Tabuteau responded that Auvelity is a proprietary formulation designed to deliver unique pharmacokinetic effects. He added that the drug’s efficacy, safety and tolerability have been demonstrated in clinical trials. In a placebo-controlled Phase 3 study recruiting 327 participants, Axsome reports that its drug meets its primary goal of showing a statistically significant reduction in depressive symptoms Measured at the sixth week according to the Depressive Episode Rating Scale.
Axsome also noted that statistically significant results were observed during the first week, or four days, after receiving the target dose. Data showed rapid onset and persistence of the effect throughout the treatment period, and Axsome filed a New Drug Application in early 2021; the FDA set a target date of August 22, 2021 for a regulatory decision. Just before that date, the agency told the company it needed more time.
The main stumbling block, Tabuteau said on Friday, was manufacturing issues. He also said the filing comes at a time when the pandemic has had a devastating impact on many companies and government agencies, including the FDA.
While Auvelity was the first pill to work by blocking NMDA, it wasn’t the first FDA-approved depression drug to work in this way.Johnson & Johnson’s Spravato also blocks this goal and its Approved in 2019 Covers the treatment of adults whose depression does not respond to earlier treatment options. The product is a version of ketamine, an ancient anesthetic abused for its hallucinogenic abilities. Although Spravato’s nasal spray is fast-acting, the drug is a Schedule III controlled substance and must be taken under the observation of a health care professional at a treatment center.
Auvelity’s drug label broadly covers the treatment of major depressive disorder in adults. The clinical trial recruited patients with varying degrees of prior experience with other depression treatments, Tabuteau said. Whether Auvelity should be used as a first- or second- or third-line treatment is up to the clinician, he said.
In clinical testing, Axsome showed no signs of psychotic symptoms or weight gain, common side effects of other depression medications. The drug’s label carries a boxed warning that increases in suicidal thoughts and behaviors are a risk to children and young adults from antidepressants. The warning is standard for depression medications, Tabuteau noted, and despite planned pediatric studies, Auvelity is not approved for use in children. Axsome is also developing the drug as a potential treatment for agitation in Alzheimer’s patients.
Axsome is still finalizing a price for Auvelity, which will be announced in the coming weeks, said Lori Englebert, Axsome’s executive vice president of commercial and business development. She added that Axsome’s goal is to set a price that ensures broad patient access, while taking into account innovation in the drug. Auvelity’s ability to start working in the first week and show relief from depressive symptoms in the second week “is incredibly differentiated in the market right now,” Englebert said.
In a research note sent to investors Friday afternoon, William Blair analyst Myles Minter wrote that his firm believes the rapid onset and differentiated mechanism of action will make Auvelity well-positioned to counter what could take six weeks Standard-of-care medication can only be started in-service.
“21 million U.S. patients are experiencing [a major depressive disorder] With episodes in the previous year and 78% of patients dissatisfied with current treatments, we believe the market is poised to be disrupted by agents like Auvelity,” Minter said.
Photo by Axsome Therapeutics
