Axsome bounces back as FDA clears depression drug

Shares in Axsome Therapeutics have rocketed on FDA approval of its depression therapy Auvelity (formerly AXS-05) – a year after its approval was held up by the regulator.

The FDA has cleared Auvelity (dextromethorphan/bupropion) for the treatment of major depressive disorder (MDD) in adults, setting up a launch in the fourth quarter of this year.

It is the first and only oral NMDA receptor antagonist to be approved for this use, and the first oral therapy with a new mechanism of action in around 60 years, said Axsome.

NMDA antagonist dextromethorphan is an ingredient found in cough syrups, while bupropion is an established antidepressant that was originally developed by GSK and sold as Wellbutrin. In this product, bupropion is designed to increase levels of dextromethorphan in the blood and extend its half-life.

On a conference call, Axsome chief executive Herriot Tabuteau said the company was pleased with the approved label for Auvelity, particularly its broad indication in MDD and wording that indicates it is rapid-acting, with efficacy starting just a week after dosing starts and lasting for at least six weeks, as found in the company's GEMINI phase 3 trial.

There is still a pressing need for antidepressant therapies that can start to work more quickly than current tricyclic or selective serotonin reuptake inhibitor drugs can take weeks to elevate mood, placing severely affected patients at risk of self harm before they kick in.

Auvelity isn't the first NMDA-targeting antidepressant to reach the market. That status goes to Johnson & Johnson's Spravato (esketamine), which was approved in March 2019 and is administered as a nasal spray twice a week for four weeks. However, it has a broader label as unlike J&J's drug it is indicated for use in previously-untreated MDD.

Axsome's drug was given a breakthrough designation from the FDA, reflecting the need for new treatment options in patients at increased risk of self harm or suicide, and was also given a priority review.

The biotech hasn't revealed much information about the reasons for the delay in getting approval, but said in an SEC filing in June this year that it had agreed to "post-marketing commitments" proposed by the FDA, without going into details.

There's no word yet on its pricing, but for comparison, Spravato was launched with an annual price tag of around $32,400, which the Institute for Clinical and Economic Review (ICER) concluded was around 25% to 52% too high to be cost effective.

Auvelity is the first drug Axsome has taken through to regulatory approval, but could be the first of a string of new products for the company, according to Tabuteau.

Next up is AXS-07 (meloxicam/rizatriptan) for acute treatment of migraine, which was turned down by the FDA at its first attempt in May but could be resubmitted in the coming months. Following after is AXS-12 (reboxetine) for narcolepsy, which could be filed in 2023.

In addition to its pipeline candidates, Axsome also has US rights to Jazz Pharma's dual-acting dopamine and norepinephrine reuptake inhibitor Sunosi (solriamfetol), used to improve wakefulness in adults living with excessive daytime sleepiness (EDS) due to narcolepsy or obstructive sleep apnea (OSA).

Axsome acquired rights to the product in May, and reported almost $9 million in sales in the second quarter.

Photo by Sydney Sims on Unsplash