Axsome’s Auvelity Wins FDA Approval as First Rapid-Acting Oral Treatment for Depression

Axsome Therapeutics’ extended-release tablets of Auvelity (dextromethorphan HBr -bupropion HCl) has been approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD).

Auvelity offers many firsts, including being the first and only rapid-acting oral medication and first and only oral N-methyl D-aspartate (NMDA) receptor antagonist approved for the treatment of MDD.

What sets Auvelity apart from other antidepressants on the market is its ability to act rapidly. Compared to the six to eight weeks that it typically takes conventional antidepressants to take effect, Auvelity’s effects can be seen in as little as a week.

Additionally, Axsome says Auvelity is the first oral MDD medication with a new mechanism of action to hit the market in more than 60 years.

While Johnson & Johnson’s NMDA receptor antagonist Spravato (nasal spray) was first approved by the FDA in 2019 for use in adults with treatment-resistant depression (TRD) and then for MDD in 2020, it has a narrower label than Auvelity, which can be used as a front-line treatment.

Auvelity has dual action as it acts on both the NMDA receptor and the sigma-1 receptor in the brain through its two main active ingredients, bupropion and dextromethorphan, respectively.

The FDA granted Auvelity Breakthrough Therapy designation in March 2019. Axsome said it expects to launch Avuelity in the fourth quarter and that its price will be set in the upcoming weeks.

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The approval of a new medication for the treatment of depression is significant given the limited treatment options and rising rates of the condition, which increased even more so during the COVID-19 pandemic.

“Over 20 million American adults experienced major depressive disorder each year prior to the COVID-19 pandemic. These numbers increased dramatically during the pandemic with approximately thirty percent of adults in the US or more than 80 million Americans experiencing elevated symptoms of depression,” said Michael Pollock, chief executive officer of the Depression and Bipolar Support Alliance (DBSA), a national patient advocacy organization, in a press release from Axsome.

“The need for new treatment options, particularly those with new mechanisms of action, could not be clearer and more urgent for those living with, or impacted by, major depressive disorder,” said Pollock.

Auvelity’s approval was based on clinical data from 1,100 patients with depression. In the Gemini placebo-controlled study, Auvelity had a statistically significant improvement in depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at Week 6 compared to placebo, which was the study’s primary endpoint.

The difference in change in MADRS total scores from baseline between Auvelity and placebo was statistically significant at Week 1 and Week 2.

In a confirmatory study called Ascend, Auvelity was found to be statistically significantly superior to bupropion sustained-release tablets 105 mg twice daily on the primary outcome measure, which evaluated an average of MADRS scores measured as a change from baseline from Week 1 to Week 6.

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“With symptom improvement happening at week one and then remission happening by week two, the combination of those two is incredibly differentiating in the marketplace right now,” Lori Englebert, Axsome’s EVP, commercial and business development, said. “If you look at the high unmet need that remains in the market — two-thirds of patients don’t achieve remission and physicians are now moving toward remission as the goal of treatment — we’re pretty excited about the product.”

Axsome also has a patient support program called “Auvelity On My Side” that the company says will offer comprehensive patient support services, including the Auvelity On My Side Savings Card to help make treatment more affordable for eligible commercially-insured patients. Other features of the program include a samples program, prior authorization support and other patient support tools. Axsome says all of the programs will be available upon launch.

To reach approval, Axsome had to address some concerns that the FDA had raised related to chemistry, manufacturing and controls (CMC), which were resolved early in the year, according to Axsome.

Auvelity’s approval comes after Axosome’s migraine treatment AXS-07 was rejected by the FDA in May. The company is also developing drugs for narcolepsy and fibromyalgia, which could have new drug approval (NDA) filings in 2023.

In addition to those candidates, Axsome acquired Sunosi, a drug for sleep apnea and narcolepsy, from Jazz Pharmaceuticals for $53 million this year. The med brought in $58 million in sales last year for Jazz.