Australian biotech's cortisol blocker ineffective in phase 2 depression study

Actinogen Medical's cortisol blocker, Xanamem, has fallen short of expectations in a phase 2 study aimed at treating depression, prompting the Australian biotech company to shift its focus to its potential applications in Alzheimer's disease. Xanamem is designed to inhibit the 11β-HSD1 enzyme to curb the excessive production of cortisol, a stress hormone, in brain cells.

The recent results stem from a phase 2 trial known as XanaCIDD, which involved 167 participants suffering from cognitive dysfunction and major depressive disorder. These individuals were administered either 10 mg of Xanamem or a placebo over a six-week period. The primary objective of the study was to measure improvements in attention and memory through computerized tests. However, the outcomes revealed similar improvements in both the Xanamem and placebo groups, with enhancements of 0.3 points and 0.4 points, respectively.

Actinogen speculated that the unexpectedly substantial improvement in the placebo group might have hindered the trial's ability to detect any short-term cognitive benefits of Xanamem. Consequently, the company's stock plummeted by 60% following the news, although its previously low share price rendered the impact negligible; it closed at 3 Australian cents compared to its previous trading price of 7 cents.

Despite the setback, Actinogen's leadership emphasized the positive aspects of the data. Notably, Xanamem demonstrated a "clinically significant" 1.5-point improvement in the MADRS depression score at the six-week mark compared to the placebo group. A 2.7-point improvement at four weeks was deemed "statistically significant." Additionally, a subgroup of 81 patients with milder depression experienced a 3.6-point increase in MADRS scores by the end of the treatment period.

Dr. Dana Hilt, Actinogen’s Chief Medical Officer, expressed optimism about the results, stating, "This encouraging result on depression is very positive to the whole Xanamem program and confirms 10 mg daily is an active clinical dose with the ability to potentially modify underlying biological processes in the brain." Hilt added that the company would continue to scrutinize the topline data and the larger dataset to better comprehend the complete results and determine future steps for the depression program. Hilt also noted that the unexpected placebo effect on cognition might have obscured the pro-cognitive benefits of Xanamem observed in previous studies.

CEO Steven Gourlay reiterated that the firm's primary focus remains on an ongoing phase 2b trial, which aims to assess Xanamem's efficacy in slowing or halting the progression of Alzheimer's disease over a 36-week period. Unlike the depression study, the Alzheimer's trial will employ a "broader range of tests" to measure cognitive function.

Gourlay and Hilt both underscored that the recent trial results do not diminish the potential for Xanamem in treating Alzheimer's disease. Given that cortisol is implicated in the underlying biology of long-term disease progression, as evidenced by functional and cognitive decline, they remain optimistic about the drug’s prospects.

In summary, while Xanamem did not meet its primary endpoint in the phase 2 depression study, Actinogen Medical remains hopeful about its potential application in Alzheimer's disease, supported by encouraging data on depression and ongoing research efforts.