- A drug recently approved to treat a type of depression has now also scored positive results in a late-stage clinical trial testing it against a common symptom of Alzheimer’s disease.
- Axsome Therapeutics, the drug’s developer, said Monday that it was significantly better than a placebo at both delaying and preventing the recurrence of agitation. While estimates vary, some hold that roughly 70% of patients with Alzheimer’s experience this symptom, which can include aggressive behavior, emotional distress or irritability. The Food and Drug Administration has yet to approve a treatment specifically for Alzheimer’s agitation.
- Axsome’s drug, called AXS-05, previously succeeded in a Phase 2/3 study targeting the same indication. In a statement, Axsome CEO Herriot Tabuteau said the company plans to discuss these clinical findings with the FDA.
Axsome’s share price, which ticked past $75 Monday morning, has tripled since June.
Much of that gain has to do with AXS-05, an oral tablet that combines two drugs — one of which, bupropion, is used to treat depression. In August, the FDA approved AXS-05 for adults with major depressive disorder, a decision that hinged on positive results from a nearly 330-person clinical trial. Axsome now sells its drug under the brand name Auvelity for that indication.
Auvelity only became commercially available in the U.S. last month. But, already, some on Wall Street have big expectations for it. Chris Howerton, an analyst at the investment firm Jefferies, has predicted the drug could generate around $1.6 billion in annual sales from the major depressive disorder indication. Meanwhile, Cowen & Co. analyst Joseph Thome estimates an approval in Alzheimer’s agitation could lead to peak U.S. sales of $750 million in 2031.
According to Axsome, the latest clinical trial results show a 3.6-fold lower risk of agitation relapse for the participants taking AXS-05 compared to those on placebo. The treatment arm also had a lower rate of relapse, at 7.5%, versus the nearly 26% seen in the control group during the double-blind portion of the study.
“Agitation occurs in the majority of patients with Alzheimer’s disease and there are currently no treatments approved for this condition,” Jeffrey Cummings, director emeritus of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, said in the Monday statement from Axsome. “AXS-05 could potentially fill this high unmet medical need for patients and their caregivers, if approved, based on the observed positive efficacy and favorable safety and tolerability results.”
Axsome structured the trial to have an open-label portion at the start, during which a total of 178 participants were given AXS-05 for up to nine weeks and evaluated on how well the drug seemed to work. Axsome said that, over this period, patients experienced “rapid, substantial, and statistically significant improvement compared to baseline in agitation symptoms.”
The trial then proceeded into a double-blind phase in which 108 patients were randomized and 55 were switched to placebo.
On safety, Axsome said the rates of adverse events observed in the double-blind phase were 28% in the AXS-05 group and 22% in the placebo group. Researchers documented two serious adverse events in the control arm — a cardiac arrest and a femur fracture — along with one in the drug arm that was later determined to be unrelated to AXS-05.
In a note to clients, Howerton highlighted how Axsome had initially aimed to enroll 260 participants in its trial. “As a result, management had been cautious [heading] into the readout,” he wrote, as a smaller enrollment would impact the trial's powering and could make it more difficult to achieve statistical significance.
“Thus, today's data are an upside surprise,” Howerton added.