Presented with upbeat Alzheimer's agitation data, FDA sees another 'breakthrough' in Axsome's AXS-05
Axsome Therapeutics’ surprise win in a late-stage Alzheimer’s study, unveiled just two months ago, has registered with regulators. The New York-based biotech has notched a breakthrough therapy designation for AXS-05 for the indication, its second after major depressive disorder.
So what’s the big deal here? The drug is an oral agent “with multimodal activity” consisting of two components: dextromethorphan, an NMDA receptor antagonist, and bupropion — whose main purpose is to slow down the metabolism of the former.
In the pivotal Phase II/III ADVANCE-1 study, patients treated with AXS-05 saw their Cohen-Mansfield Agitation Inventory (CMAI) total score decrease in 5 weeks from baseline by 15.4 points on average, compared to 11.5 points for placebo (p=0.010). It was also superior to bupropion alone (p<0.001), proving the necessity of a combo.
The CMAI score measures some of the most visible behaviors as reported by caregivers of Alzheimer’s patients, including episodes of screaming or hitting.
“This FDA Breakthrough Therapy designation is an important milestone in the development of AXS-05 for Alzheimer’s disease agitation, a serious, prevalent, and debilitating condition for which there is currently no approved therapy,” CEO Herriot Tabuteau said in a statement.
Analysts tracking Axsome hadn’t been paying much attention to Alzheimer’s agitation, focusing instead on MDD, where the company is lining up a near-term application with the FDA after reporting upbeat data in one of the toughest fields in R&D.
But after consulting with physicians, Cowen analyst Joseph Thome recently noted that the disease has historically been difficult to treat, and that the results were impressive especially given the placebo group actually performed better than expected.
“We expect that AXS-05 will be successfully developed for the indication following another Ph. III study and model $750MM in peak U.S. sales,” he wrote, adding to the $2 billion opportunity with MDD.
The fact that no other drug has ever been approved for the specific use, though, can be a double-edged sword. Otsuka’s Avanir has previously scored a Phase III win for AVP-786 — deudextromethorphan hydrobromide [d6-DM]/quinidine sulfate) — only to be disappointed in the second.
Axsome seems to have the FDA on its side for now. And that has investors stoked, sending shares up 11.33% to $85.29.