Atossa Therapeutics Announces Full Results from Phase 2 KARISMA-Endoxifen Study Demonstrating Statistically Significant Reductions in Mammographic Breast Density
Atossa Therapeutics (NASDAQ: ATOS) announced full results from its Phase 2 KARISMA-Endoxifen trial, showing significant reductions in mammographic breast density (MBD) in premenopausal women. The randomized, double-blind study of 240 women aged 40-55 tested 1mg and 2mg doses of (Z)-endoxifen against placebo over six months.
The 1mg dose reduced MBD by 17.3 percentage points and the 2mg dose by 23.5 percentage points (both p<0.01), compared to 0.27 points for placebo. The 1mg dose showed no significant difference in adverse events versus placebo, while the 2mg dose had higher rates of side effects. Plasma concentrations were 4.8 ng/mL and 9.7 ng/mL for 1mg and 2mg doses respectively.
Atossa Therapeutics (NASDAQ: ATOS) ha annunciato i risultati completi del suo studio di Fase 2 KARISMA-Endoxifen, evidenziando una significativa riduzione della densità mammografica del seno (MBD) nelle donne in premenopausa. Lo studio randomizzato, in doppio cieco, ha coinvolto 240 donne di età compresa tra 40 e 55 anni, testando dosi di 1mg e 2mg di (Z)-endoxifene contro un placebo per sei mesi.
La dose di 1mg ha ridotto la MBD di 17,3 punti percentuali e la dose di 2mg di 23,5 punti percentuali (entrambe p<0.01), rispetto a 0,27 punti per il placebo. La dose di 1mg non ha mostrato differenze significative negli eventi avversi rispetto al placebo, mentre la dose di 2mg ha avuto tassi più elevati di effetti collaterali. Le concentrazioni plasmatiche erano di 4,8 ng/mL e 9,7 ng/mL per le dosi di 1mg e 2mg rispettivamente.
Atossa Therapeutics (NASDAQ: ATOS) anunció los resultados completos de su ensayo de Fase 2 KARISMA-Endoxifen, mostrando reducciones significativas en la densidad mamográfica del seno (MBD) en mujeres premenopáusicas. El estudio aleatorizado, a doble ciego, incluyó a 240 mujeres de entre 40 y 55 años y probó dosis de 1mg y 2mg de (Z)-endoxifeno frente a placebo durante seis meses.
La dosis de 1mg redujo la MBD en 17,3 puntos porcentuales y la de 2mg en 23,5 puntos porcentuales (ambas p<0.01), en comparación con 0,27 puntos para el placebo. La dosis de 1mg no mostró diferencias significativas en eventos adversos en comparación con el placebo, mientras que la dosis de 2mg tuvo tasas más altas de efectos secundarios. Las concentraciones plasmáticas fueron de 4,8 ng/mL y 9,7 ng/mL para las dosis de 1mg y 2mg, respectivamente.
아토사 테라퓨틱스(NASDAQ: ATOS)는 전임신 여성에서 유방 촬영 밀도(MBD)의 상당한 감소를 보여주는 Phase 2 KARISMA-Endoxifen 시험의 전체 결과를 발표했습니다. 40세에서 55세 사이의 240명의 여성을 대상으로 한 무작위 이중 맹검 연구에서 (Z)-엔도시펜의 1mg 및 2mg 용량을 6개월 동안 위약과 비교했습니다.
1mg 용량에서는 MBD가 17.3 퍼센트 포인트 감소하였고, 2mg 용량에서는 23.5 퍼센트 포인트 감소하였으며(둘 다 p<0.01), 위약은 0.27 포인트 감소만 있었습니다. 1mg 용량은 위약과 비교하여 유해 사건에서 유의미한 차이를 보이지 않았지만, 2mg 용량은 부작용 비율이 높았습니다. 1mg와 2mg 용량의 혈장 농도는 각각 4.8 ng/mL와 9.7 ng/mL였습니다.
Atossa Therapeutics (NASDAQ: ATOS) a annoncé les résultats complets de son essai de Phase 2 KARISMA-Endoxifen, montrant des réductions significatives de la densité mammaire par mammographie (MBD) chez les femmes préménopausées. L'étude randomisée, en double aveugle, a impliqué 240 femmes âgées de 40 à 55 ans et a testé des doses de 1mg et 2mg de (Z)-endoxifène par rapport à un placebo pendant six mois.
La dose de 1mg a réduit la MBD de 17,3 points de pourcentage et la dose de 2mg de 23,5 points de pourcentage (toutes deux p<0,01), contre 0,27 points pour le placebo. La dose de 1mg n'a montré aucune différence significative dans les événements indésirables par rapport au placebo, tandis que la dose de 2mg a présenté des taux d'effets secondaires plus élevés. Les concentrations plasmatiques étaient de 4,8 ng/mL et 9,7 ng/mL pour les doses de 1mg et 2mg respectivement.
Atossa Therapeutics (NASDAQ: ATOS) hat die vollständigen Ergebnisse der Phase-2-Studie KARISMA-Endoxifen bekannt gegeben, die signifikante Reduzierungen der mammografischen Brustdichte (MBD) bei prämenopausalen Frauen zeigen. Die randomisierte, doppelblinde Studie umfasste 240 Frauen im Alter von 40 bis 55 Jahren und testete Dosen von 1mg und 2mg (Z)-Endoxifen im Vergleich zu Placebo über einen Zeitraum von sechs Monaten.
Die 1mg-Dosis reduzierte die MBD um 17,3 Prozentpunkte und die 2mg-Dosis um 23,5 Prozentpunkte (beide p<0,01), verglichen mit 0,27 Punkten für das Placebo. Die 1mg-Dosis zeigte keine signifikanten Unterschiede in der Häufigkeit unerwünschter Ereignisse im Vergleich zum Placebo, während die 2mg-Dosis höhere Raten von Nebenwirkungen hatte. Die Plasmakonzentrationen lagen bei 4,8 ng/mL und 9,7 ng/mL für die Dosen von 1mg und 2mg.
- Statistically significant reduction in mammographic breast density with both doses (p<0.01)
- 1mg dose showed comparable efficacy with fewer side effects than 2mg dose
- Lower plasma concentrations achieved desired effects compared to traditional tamoxifen
- Favorable safety profile for 1mg dose, showing no significant adverse events versus placebo
- 2mg dose associated with increased side effects (hot flashes, night sweats, vaginal discharge)
Insights
The Phase 2 KARISMA-Endoxifen trial results represent a significant breakthrough in breast cancer prevention. The study demonstrated that a 1 mg dose of (Z)-endoxifen reduced mammographic breast density by
The plasma concentrations achieved (4.8 ng/mL for 1 mg and 9.7 ng/mL for 2 mg) indicate excellent bioavailability. Most notably, the lower dose demonstrated similar efficacy to historical tamoxifen studies while maintaining a superior safety profile. This positions (Z)-endoxifen as a potentially transformative preventative therapy for premenopausal women with dense breast tissue, addressing both a significant risk factor and a diagnostic challenge in breast cancer detection.
These compelling Phase 2 results significantly strengthen Atossa's market position in breast cancer prevention. With a market cap of
The positive data validates Atossa's development strategy and positions them well for Phase 3 trials. Success in this indication could lead to significant market opportunities, particularly given the preventative nature of the treatment and the large target population. The favorable safety profile at the 1 mg dose could accelerate regulatory pathway and enhance commercial prospects.
1 MG Dose (Z)-Endoxifen Shows Potential as a Well-Tolerated, Preventative Therapy for Premenopausal Women at Risk of Developing Breast Cancer
Data to be Presented in a Poster Spotlight Session During the 2024 San Antonio Breast Cancer Symposium
SEATTLE, Dec. 11, 2024 (GLOBE NEWSWIRE) -- Atossa Therapeutics, Inc. (Nasdaq: ATOS) (“Atossa” or the “Company”), today announced full results from its Phase 2 KARISMA-Endoxifen trial conducted at the Karolinska Institute in Stockholm, Sweden. The data, which will be presented during a Poster Spotlight Session at the 2024 San Antonio Breast Cancer Symposium, highlight the potential of low-dose (Z)-endoxifen to significantly reduce mammographic breast density (MBD), a key risk factor for breast cancer, while demonstrating a favorable safety profile. Atossa is a clinical stage biopharmaceutical company developing innovative medicines in areas of significant unmet medical need in oncology with a focus on breast cancer.
The randomized, double-blind, placebo-controlled study enrolled 240 premenopausal women aged 40-55, randomized to one of three arms: placebo, 1 mg, or 2 mg of daily oral (Z)-endoxifen for six months. The study aimed to evaluate reductions in MBD and assess safety and tolerability.
Results showed that the 1 mg dose of (Z)-endoxifen reduced 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), compared to a minimal change in the placebo group of 0.27 percentage points. Plasma concentrations for (Z)-endoxifen were measured at 4.8 ng/mL and 9.7 ng/mL for the 1 mg and 2 mg arms, respectively, highlighting the effectiveness of the lower dose in achieving significant reductions. Importantly, no significant differences in adverse events were observed between the 1 mg dose and placebo. The 2 mg dose was associated with higher rates of hot flashes, night sweats and vaginal discharge.
“These results underscore the promise of (Z)-endoxifen as a preventative therapy for women with dense breast tissue,” said Steven Quay, M.D., Ph.D., Atossa’s President and Chief Executive Officer. “The ability to achieve statistically significant reductions in mammographic breast density with a low dose of (Z)-endoxifen that also avoids toxicity issues common to tamoxifen suggests this therapy could be particularly suitable for premenopausal women and could represent an important breakthrough in breast cancer prevention.”
Mammographic breast density, an independent risk factor for breast cancer, not only complicates tumor detection on mammograms, but is also associated with an increased likelihood of developing the disease. The KARISMA-Endoxifen trial results align with outcomes observed in prior studies using tamoxifen, demonstrating comparable reductions in MBD with lower plasma concentrations and fewer side effects, emphasizing the potential of (Z)-endoxifen as a safer and more targeted alternative.
Presentation Details:
Poster Spotlight Session 16
Title: PS16-05 Primary Breast Cancer Prevention Using Oral Endoxifen
- Description: Evaluates the effectiveness of low-dose (Z)-endoxifen in reducing mammographic breast density, a significant risk factor for breast cancer.
- Poster Details: Per Hall, Karolinska Institutet, 5:30-6:00 pm, Thursday, December 12
A link to the poster presentation will be made available on Atossa Therapeutics’ website at the time of the presentation. For additional information, please visit the SABCS website: https://sabcs.org.
About (Z)-Endoxifen
(Z)-endoxifen is one of the most potent Selective Estrogen Receptor Modulator (SERM) for estrogen receptor inhibition and may cause estrogen receptor degradation. It has also been shown to have efficacy in the setting of patients with tumor resistance to other hormonal treatments. In addition to its potent anti-estrogen effects, (Z)-endoxifen has been shown to target PKCβ1, a known oncogenic protein, at clinically attainable blood concentrations. Finally, (Z)-endoxifen appears to deliver similar or even greater bone agonistic effects while resulting in little or no endometrial proliferative effects compared with standard treatments, like tamoxifen.
Atossa is developing a proprietary oral formulation of (Z)-endoxifen that is encapsulated to bypass the stomach, as acidic conditions in the stomach convert a significant proportion of (Z)-endoxifen to the inactive (E)-endoxifen. Atossa’s (Z)-endoxifen has been shown to be well tolerated in Phase 1 studies and in a small Phase 2 study of women with breast cancer. (Z)-endoxifen is currently being studied in five Phase 2 trials: one in healthy women with measurable breast density, one in women diagnosed with ductal carcinoma in situ, and three other studies including the EVANGELINE study and two I-SPY studies in women with ER+/HER2- breast cancer. Atossa’s (Z)-endoxifen is protected by four issued U.S. patents and numerous pending patent applications.
About Atossa Therapeutics
Atossa Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing innovative medicines in areas of significant unmet medical need in oncology with a focus on using (Z)-endoxifen to prevent and treat breast cancer. For more information, please visit www.atossatherapeutics.com.
FORWARD LOOKING STATEMENTS
This press release contains certain information that may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. We may identify these forward-looking statements by the use of words such as “expect,” “potential,” “continue,” “may,” “will,” “should,” “could,” “would,” “seek,” “intend,” “plan,” “estimate,” “anticipate,” “believe,” “design,” “predict,” “future,” or other comparable words. All statements made in this press release that are not statements of historical fact, including statements regarding data related to the (Z)-endoxifen program, the safety, tolerability and efficacy of (Z)-endoxifen, the potential of (Z)-endoxifen as a breast cancer prevention and treatment agent, the expected design and enrollment of trials and timing of data and related publications, and the potential milestones and growth opportunities for the Company, are forward-looking statements. Forward-looking statements in this press release are subject to risks and uncertainties that may cause actual results, outcomes, or the timing of actual results or outcomes, to differ materially from those projected or anticipated, including risks and uncertainties associated with: macroeconomic conditions and increasing geopolitical instability; the expected timing of releasing data; any variation between interim or preliminary and final clinical results or analysis; actions and inactions by the FDA and foreign regulatory bodies; the outcome or timing of regulatory approvals needed by Atossa, including those needed to continue our planned (Z)-endoxifen trials; our ability to satisfy regulatory requirements; our ability to remain compliant with the continued listing requirements of the Nasdaq Stock Market; our ability to successfully develop and commercialize new therapeutics; the success, costs and timing of our development activities, including our ability to successfully initiate or complete our clinical trials, including our (Z)-endoxifen trials; our anticipated rate of patient enrollment; our ability to contract with third-parties and their ability to perform adequately; our estimates on the size and characteristics of our potential markets; our ability to successfully defend litigation and other similar complaints and to establish and maintain intellectual property rights covering our products; whether we can successfully complete our clinical trial of oral (Z)-endoxifen in women with mammographic breast density and our trials of (Z)-endoxifen in women with breast cancer, and whether the studies will meet their objectives; our expectations as to future financial performance, expense levels and capital sources, including our ability to raise capital; our ability to attract and retain key personnel; our anticipated working capital needs and expectations around the sufficiency of our cash reserves; and other risks and uncertainties detailed from time to time in Atossa’s filings with the Securities and Exchange Commission, including without limitation its Annual Reports on Form 10-K and Quarterly Reports on 10-Q. Forward-looking statements are presented as of the date of this press release. Except as required by law, we do not intend to update any forward-looking statements, whether as a result of new information, future events or circumstances or otherwise.
Contact:
Michael Parks
VP, Investor and Public Relations
484-356-7105
michael.parks@atossainc.com
FAQ
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