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Axsome, beating the odds, finds success treating Alzheimer’s agitation

Axsome Therapeutics said Monday that one of its experimental drugs succeeded in a late-stage study of Alzheimer’s disease patients who show signs of agitation.On average, the patients who were given Axsome’s drug, called AXS-05, had significantly larger drops on a scale that rates agitation than those given a placebo. AXS-05 also performed better than a comparator drug included in the study. Axsome said its drug was well tolerated, with 1% to 2% of patients experiencing serious side effects across all the study arms and none deemed related to AXS-05.  Investors reacted positively to the results, sending Axsome’s share price up 43% to $109.13 by market’s open Monday. The biotech said it plans to discuss its data with the Food and Drug Administration. Currently, there are no FDA-approved treatments for Alzheimer’s disease agitation.

Landing positive data from a late-stage study can be particularly challenging for drugmakers going after brain or mood disorders. These studies are often built around subjective endpoints and scales that rely on patient responses or doctor interpretations, which can confound results. Many neuroscience programs have been derailed by better-than-expected responses from patients taking placebos.

Axsome, though, has bucked the odds, having reported two positive late-stage readouts for AXS-05 since December. The first, from a Phase 3 trial called GEMINI, showed the drug significantly outperformed placebo in improving symptoms of depression for patients with major depressive disorder. Axsome expects to submit AXS-05 for approval in that condition sometime between October and December.

The second, from a Phase 2/3 trial called ADVANCE-1, showed Alzehimer’s patients who were given the drug experienced, on average, a 15.4-point reduction in agitation over a five-week period. Patients in the placebo group, meanwhile, experienced an 11.5-point reduction. The trial measured patients’ agitation levels using the Cohen Mansfield Agitation Inventory, a rating scale that caregivers use to measure 29 agitated behaviors, including things such as pacing, restlessness, screaming, shouting and physical aggression.

According to Axsome, the results represent a 48% average reduction in agitation for patients treated with AXS-05 and a 38% reduction for those put on placebo. The company also said that 73% of patients receiving its drug achieved what’s considered a “clinical response” on the rating scale versus 57% receiving placebo.

“Agitation occurs in the majority of patients with Alzheimer’s disease, is very distressing to patients and their families, and is associated with greater risk of institutionalization and accelerated progression to severe dementia and death,” said Jeffrey Cummings, director emeritus of the Cleveland Clinic Lou Ruvo Center for Brain Health, in a statement released by Axsome.​

“Given the lack of approved treatments for Alzheimer’s disease agitation, and the safety concerns and modest or uncertain efficacy of currently used off-label treatments, the AXS-05 study results represent a meaningful step forward toward urgently needed treatment for this serious complication of Alzheimer’s disease,” Cummings added.

AXS-05 is an oral drug made of two components: dextromethorphan and bupropion. The dextromethorphan component effectively regulates a neurotransmitter that controls mood and agitation, while the bupropion component is meant to increase the amount of dextromethorphan available in the body.

Axsome said the ADVANCE-1 data found AXS-05 to be superior to bupropion alone, which was the comparator drug, as measured by the rating scale. The company claims these data provide evidence that the dextromethorphan component is contributing to patient improvement.