Depressed man.
In August, the Food and Drug Administration (FDA ) approved Axsome Therapeutics’ Auvelity (dextromethorphan/bupropion) extended release tablets for the treatment of major depressive disorder (MDD) in adults. Auvelity combines two decades’ old active ingredients; dextromethorphan, which is a cough suppressant, and bupropion, an anti-depressant. Still, Auvelity is the first orally administered product with a novel mechanism of action to enter the MDD market in more than 60 years.
Auvelity’s rapid onset of action represents a breakthrough in the MDD market, in which there exists unmet need for drugs that can demonstrate rapid antidepressant effects. The current standard of care includes selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs). The antidepressant effects from these medications occur after weeks of treatment.
The fast-acting and (presumably) sustained antidepressant effects of Auvelity are bolstered by the fact that in a Phase 3 study taking the drug was not associated with weight gain. Many currently available anti-depressants are associated with weight increase.
Two pivotal trials supported Auvelity’s approval: The GEMINI placebo-controlled study and the ASCEND study comparing Auvelity to bupropion sustained-release tablets. Notably, in a comparative trial - the ASCEND study - Auvelity was found to be statistically significantly superior to bupropion on the primary outcome measure.
Despite the demonstrated advantages of Auvelity in clinical trials, there will be pricing and reimbursement challenges for this new product, as there are for most newly approved drugs in classes in which there are large numbers of (cheaper) treatment alternatives. Although Axsome has not yet announced a price, it’s anticipated that it will be a relatively expensive product compared with generic SSRIs and SNRIs, which are very well-established on the MDD market. With a comparatively high expected price, Auvelity may see its use restricted by payers to second and later lines of therapy.
This is not to say Auvelity will not be covered. It probably will be placed on formulary by many commercial insurers as well as all Medicaid plans, assuming Axsome Therapeutics is participating in the Medicaid Drug Rebate Program. Further, as an antidepressant it will enjoy protected drug class status, and so it should also be covered by all Medicare Part D plans.
However, coverage is a complex phenomenon. Coverage isn’t merely a binary decision of being on formulary or excluded. The majority of newly approved drugs eventually find a place on the formulary. But, it’s their position on the formulary that matters.
Here, access is a function of the conditions of reimbursement that payers impose, such as patient cost-sharing, prior authorization, step edits, quantity limits, and indication restrictions. And these conditions of reimbursement depend on a host of factors, such as price per unit, rebates, therapeutic interchangeability with other products, clinical- and cost-effectiveness, and budgetary impact.
Overcoming market access hurdles will be a challenge for Auvelity’s sponsor, Axsome Therapeutics. But, a favorable efficacy and safety profile will likely help to facilitate patient access.
