Axsome Therapeutics’ depression drug designed to start working quickly now has its long-awaited approval one year after the target FDA decision date. The regulatory nod announced Friday makes the product the first new oral drug in decades to target a new depression target.
The drug, which was known in its development under the code name AXS-05, will be marketed under the brand name Auvelity. New York-based Axsome plans to launch the twice-daily pill in the fourth quarter.
With the regulatory approval, Auvelity is poised to join a depression drug market filled with older products, many of which take a long time to start working and come with serious side effects. Many of these drugs work by targeting monoamine oxidase (MAO), blocking this enzyme’s ability to remove key neurotransmitters from the brain. MAOIs are widely prescribed, but a large contingent of patients do not respond to them, and for those who do, the effect can take six weeks or more to begin.
Auvelity may be a new drug, but its two main components are older drugs. The product combines buproprion, the active ingredient in GSK’s old antidepressant and smoking cessation drug Wellbutrin, with dextromethorphan, an ingredient in many cough medicines. Dextromethorphan crosses the blood-brain barrier to target the part of the brain that causes coughing. Auvelity uses dextromethorphan to block the NMDA receptor, which the company says makes it the first new oral depression drug in more than 60 years that works by targeting a target other than MAO. The bupropion part of the drug increases the levels of dextromethorphan in the blood. Axsome combines both active ingredients with a proprietary technology that modulates the delivery of each compound.
On a conference call Friday to discuss the approval, one financial analyst asked whether doctors could try to circumvent Auvelity by prescribing its two generic components together. CEO Herriot Tabuteau responded that Auvelity is a proprietary formulation designed to provide a distinct pharmacokinetic effect. He added that the drug’s efficacy, safety and tolerability have been proven in clinical trials. In a placebo-controlled phase 3 study involving 327 participants, Axsome reported that its drug met the primary goal of showing a statistically significant reduction in depression symptoms at week six, as measured by the Depressive Episode Rating Scale.
Axsome also noted that statistically significant results were seen in the first week – four days after receiving the target dose. With data showing a rapid onset of effect and duration of that effect throughout the treatment period, Axsome submitted a new drug application in early 2021; The FDA has set an August 22, 2021 target date for a regulatory decision. Just before that date, the agency told the company it needed more time.
Tabuteau said Friday that the underlying detention is an issue in the proceedings. He also said the filing comes amid the pandemic’s devastating effects on many companies and government agencies, including the FDA.
Although Auvelity is the first pill to work by blocking NMDA, it is not the first FDA-approved depression drug to work this way. Johnson & Johnson’s Spravato also blocked that target and hers 2019 approval covers the treatment of adults whose depression has not responded to previous lines of therapy. This product is a version of ketamine, an old anesthetic abused for its ability to induce hallucinations. Although Spravato Nasal Spray offers a fast-acting effect, the drug is a Schedule III controlled substance that must be taken under the supervision of a medical professional in a treatment facility.
The drug label for Auvelity primarily covers the treatment of major depressive disorder in adults. Tabuteau said the clinical trials included patients who had varying levels of prior experience with other depression therapies. Whether Auvelity should be prescribed as first-line treatment or as second- or third-line therapy is up to the clinician, he said.
In clinical tests, Axsome said there was no indication of psychotic symptoms or weight gain, which are common side effects of other depression drugs. The drug’s label contains a black box warning noting that an increase in suicidal thoughts and behavior is a risk posed by antidepressants in children and young adults. Tabuteau noted that this warning is standard for depression drugs, and Auvelity is not approved for children, although a pediatric study is planned. Axsome is also developing the drug as a potential treatment for agitation in Alzheimer’s patients.
Axsome is still finalizing Auvelity’s price, which will be announced in the coming weeks, said Lori Englebert, the company’s executive vice president of commercial and business development. She added that Axsome aims to set a price that ensures broad patient access while taking into account the drug’s innovation. Auvelity’s ability to start working in the first week and show remission of depression symptoms in the second week “is incredibly differentiating in the market right now,” Englebert said.
In a research note sent to investors Friday afternoon, William Blair analyst Miles Minter wrote that his firm believes the rapid onset of action, combined with a differentiated mechanism of action, will position Auvelity well against standard drugs that can take six weeks to start working.
“With 21 million patients in the US experiencing [a major depressive disorder] episode in the previous year and 78% of patients are dissatisfied with their current treatment, we believe the market is ripe for disruption from an agent like Auvelity,” Minter said.
Photo by Axsome Therapeutics