Atossa Therapeutics Announces Full Results from Phase 2 KARISMA-Endoxifen Study Demonstrating Statistically Significant Reductions in Mammographic Breast Density

Core Insights - Atossa Therapeutics has announced promising results from its Phase 2 KARISMA-Endoxifen trial, indicating that low-dose (Z)-endoxifen may significantly reduce mammographic breast density (MBD) in premenopausal women at risk of breast cancer while maintaining a favorable safety profile [1][4]. Study Design - The trial was a randomized, double-blind, placebo-controlled study involving 240 premenopausal women aged 40-55, who were assigned to receive either a placebo, 1 mg, or 2 mg of daily oral (Z)-endoxifen for six months [2]. Results - The 1 mg dose of (Z)-endoxifen resulted in a reduction of MBD by 17.3 percentage points (p<0.01), while the 2 mg dose achieved a reduction of 23.5 percentage points (p<0.01). In contrast, the placebo group showed a minimal change of 0.27 percentage points [3]. - Plasma concentrations of (Z)-endoxifen were recorded at 4.8 ng/mL for the 1 mg group and 9.7 ng/mL for the 2 mg group, demonstrating the effectiveness of the lower dose [3]. - No significant differences in adverse events were noted between the 1 mg dose and placebo, although the 2 mg dose was associated with higher incidences of hot flashes, night sweats, and vaginal discharge [3]. Implications - The results suggest that (Z)-endoxifen could serve as a preventative therapy for women with dense breast tissue, potentially offering a safer alternative to tamoxifen with fewer side effects [4]. - The findings align with previous studies on tamoxifen, indicating comparable reductions in MBD with lower plasma concentrations and reduced side effects [4]. Presentation Details - The results will be presented during a Poster Spotlight Session at the 2024 San Antonio Breast Cancer Symposium, highlighting the effectiveness of low-dose (Z)-endoxifen in reducing MBD [5]. About (Z)-Endoxifen - (Z)-endoxifen is a potent Selective Estrogen Receptor Modulator (SERM) that may cause estrogen receptor degradation and has shown efficacy in patients resistant to other hormonal treatments. It targets PKCβ1, an oncogenic protein, and exhibits favorable bone agonistic effects with minimal endometrial proliferation compared to standard treatments like tamoxifen [6]. Company Overview - Atossa Therapeutics is a clinical-stage biopharmaceutical company focused on developing innovative medicines for significant unmet medical needs in oncology, particularly in breast cancer prevention and treatment [9].