Atossa Therapeutics Provides Five-Year (Z)-Endoxifen Treatment Update on FDA-Approved "Expanded Access" Program for a U.S. Breast Cancer Patient
Atossa Therapeutics, Inc. (ATOS) announces successful 5-year treatment of pre-menopausal ER+ breast cancer patient with (Z)-endoxifen therapy. The patient remains cancer-free with no safety issues. (Z)-endoxifen shows promise in changing breast cancer treatment paradigm.
The case of the pre-menopausal breast cancer patient treated with (Z)-endoxifen highlights a potential shift in therapeutic approaches for ER+/HER2- breast cancer. The reduction of Ki-67 expression by 50% post-neoadjuvant therapy is significant, as high levels of this protein are often associated with more aggressive tumors and poorer prognosis. The patient's positive response suggests that (Z)-endoxifen could be a promising alternative for patients with specific genetic profiles, such as a CYP2D6*4/*4 genotype, which limits the effectiveness of tamoxifen.
Furthermore, the lack of vasomotor symptoms, which are common side effects of tamoxifen, indicates a favorable tolerability profile for (Z)-endoxifen. This could improve patient adherence to treatment, a critical factor in long-term disease management. The potential for (Z)-endoxifen to offer a well-tolerated and effective treatment option could have significant implications for patient quality of life and treatment outcomes.
From a pharmacogenomics standpoint, the patient's nonfunctioning CYP2D6 variant is a key consideration. Tamoxifen, a commonly used drug in breast cancer therapy, requires conversion by the CYP2D6 enzyme to its active form. Patients with this genetic variant, therefore, experience reduced efficacy from tamoxifen. The successful use of (Z)-endoxifen in this patient could indicate a valuable alternative for those with similar genotypes.
Additionally, the patient's family history of osteoporosis, which is a contraindication for aromatase inhibitor treatment, further underscores the importance of personalized medicine. The ability to tailor treatment based on genetic makeup and contraindications could lead to more effective and safer treatment protocols. As (Z)-endoxifen becomes more widely studied, it could potentially expand treatment options for patients who are not ideal candidates for current standard therapies.
The successful five-year treatment of a patient under the FDA's Expanded Access program with (Z)-endoxifen could be an indicator of the drug's market potential. With approximately 250,000 women diagnosed with ER+ breast cancer annually in the U.S., the demand for alternative treatments that are both effective and have fewer side effects is substantial.
However, it's important to note that this is a single patient case and not a large-scale clinical trial. While the results are promising, they are not yet generalizable to the broader patient population. Nonetheless, if further studies corroborate these findings, (Z)-endoxifen could capture a significant share of the breast cancer treatment market, especially for patients with genetic profiles that make them less responsive to traditional treatments like tamoxifen.
03/19/2024 - 08:30 AM
SEATTLE, March 19, 2024 (GLOBE NEWSWIRE) -- Atossa Therapeutics, Inc. (Nasdaq: ATOS) (“Atossa” or the “Company”), today announced that the pre-menopausal, Estrogen Receptor positive (ER+) / Human Epidermal Growth Factor Receptor 2 negative (HER2-), breast cancer patient who received neoadjuvant and adjuvant (Z)-endoxifen therapy under an FDA-approved "expanded access" program has completed five years of treatment. As of the date of this press release, the patient remains cancer-free and has reported no significant safety or tolerability issues over the course of her treatment. 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.
"We believe this patient, and her successful treatment journey, is representative of the opportunity (Z)-endoxifen has to change the treatment paradigm for the approximately 250,000 women diagnosed with estrogen receptor positive breast cancer each year in the U.S.,” said Steven Quay, M.D., Ph.D., Atossa’s President and Chief Executive Officer. "The current standard of care is sub-optimal as it often requires ovarian suppression in premenopausal women and aromatase inhibitors in postmenopausal women, both of which are associated with potential short-term and long-term side effects that diminish adherence. Over five years of adjuvant treatment, her daily (Z)-endoxifen treatment has been well tolerated, and there were no vasomotor symptoms commonly associated with standard of care adjuvant pharmaceuticals. She remains cancer-free today and we are grateful to have been able to help her with a difficult treatment problem.”
Patient / Treatment Background
Diagnosis. In late 2018, a 51-year-old premenopausal woman was diagnosed with a moderately differentiated invasive ductal breast carcinoma with the most frequently reported subtype: ER+, PR+, and HER2-. The initial diagnostic biopsy demonstrated that 90% of the tumor cells were ER+ and 20% expressed Ki-67, a tumor proliferation antigen. Pharmacogenomics analysis showed a CYP2D6 genotype of CYP2D6*4/*4, a nonfunctioning variant, suggesting tamoxifen would be a poor treatment option.
Other than breast cancer, the patient had no comorbidities and took no medications. Her family history was strong for osteoporosis, a contraindication for aromatase inhibitor treatment.
Neoadjuvant treatment. Neoadjuvant treatment is given in the window of time between the diagnosis and the primary treatment, which in the case of locally advanced breast cancer is surgery. The intent of neoadjuvant therapy is to slow the growth of the cancer or even shrink the cancer prior to surgery. The goal of this treatment is to help increase the effectiveness of surgery, and it has also been shown to reduce the likelihood that the cancer returns.
The FDA authorized a single-patient study under its Expanded Access or compassionate use program for this woman to receive 4 mg/day oral (Z)-endoxifen for 20 days before surgery.
Surgery. The patient had a unilateral mastectomy. After (Z)-endoxifen neoadjuvant treatment, the Ki-67 expression in the tumor was reduced 50% , from 20% to 10% . Both the relative response, a 50% reduction, and the absolute value at the time of surgery have been found in large trials to be an indicator of favorable long-term outcomes.
Adjuvant treatment. Following surgery, her physician recommended adjuvant therapy but, like many women, she was not a candidate for tamoxifen due to her low liver enzyme (CYP2D6) activity. She also did not want to take drugs to suppress her ovarian function and go into early menopause, which meant aromatase inhibitors were not an option. Given the strong and rapid response to (Z)-endoxifen, it was recommended that she continue taking (Z)-endoxifen. This led to an additional compassionate use authorization by the FDA to allow this patient to continue taking 4 mg/day (Z)-endoxifen in the adjuvant setting.
She has now completed five years of daily (Z)-endoxifen. As of the date of this press release, she has not had a recurrence of breast cancer or a new cancer in the contralateral breast, as assessed by clinical examination and mammography. Additionally, the treatment has been well tolerated, and there were no vasomotor symptoms commonly associated with tamoxifen (for example, night sweats and hot flashes).
Under the FDA Expanded Access IND program, the use of Atossa's proprietary (Z)-endoxifen is restricted to this patient only.
About FDA Expanded Access
Expanded access may be appropriate when all the following apply: the patient has a serious disease or condition, or whose life is immediately threatened by their disease or condition; there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; patient enrollment in a clinical trial is not possible; potential patient benefit justifies the potential risks of treatment; providing the investigational medical product does not interfere with investigational trials that could support a medical product's development or marketing approval for the treatment indication; alternative investigational drugs, biologics or medical devices have not yet been approved or cleared by FDA and FDA has not found these products to be safe and effective for their specific use; and alternative investigational medical product may, or may not, be effective in the treatment of the condition, and use of the product may cause unexpected serious side effects.
For more information, see the FDA website: FDA Expanded Use Website .
About (Z)-Endoxifen
Atossa is developing a proprietary oral formulation of (Z)-endoxifen that does not require liver metabolism to achieve therapeutic concentrations and is encapsulated to bypass the stomach as acidic conditions in the stomach convert a greater 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 four Phase 2 trials: one in healthy women with measurable breast density, one in women diagnosed with ductal carcinoma in situ, and two other studies including the EVANGELINE study in women with ER+/HER2- breast cancer. Atossa’s (Z)-endoxifen is protected by three issued U.S. patents and numerous pending patent applications.
About Atossa Therapeutics www.atossatherapeutics.com .
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FORWARD LOOKING STATEMENTS
What is the treatment provided to the pre-menopausal breast cancer patient by Atossa Therapeutics?
Atossa Therapeutics provided neoadjuvant and adjuvant (Z)-endoxifen therapy to the pre-menopausal, ER+ breast cancer patient.
What is the subtype of breast cancer diagnosed in the patient?
The patient was diagnosed with ER+, PR+, and HER2- subtype of breast cancer.
How long has the patient been on (Z)-endoxifen treatment?
The patient has completed five years of treatment with daily (Z)-endoxifen.
What was the patient's response to (Z)-endoxifen treatment?
The patient had a favorable response to (Z)-endoxifen treatment with no recurrence of breast cancer.
What were the significant results of the neoadjuvant treatment with (Z)-endoxifen?
The neoadjuvant treatment with (Z)-endoxifen reduced the Ki-67 expression in the tumor by 50%.
What were the reasons the patient could not take tamoxifen or aromatase inhibitors?
The patient could not take tamoxifen due to her CYP2D6 genotype and did not want to take aromatase inhibitors due to potential side effects.
How was the treatment with (Z)-endoxifen authorized by the FDA?
The treatment with (Z)-endoxifen was authorized under the FDA Expanded Access or compassionate use program.
What are the key highlights of the patient's treatment journey with (Z)-endoxifen?
The patient's treatment journey with (Z)-endoxifen has been successful, well-tolerated, and led to no recurrence of breast cancer.
What is the current status of the patient after completing five years of (Z)-endoxifen treatment?
As of the press release date, the patient remains cancer-free with no recurrence of breast cancer.
What is the restriction on the use of Atossa's proprietary (Z)-endoxifen under the FDA Expanded Access IND program?
The use of Atossa's proprietary (Z)-endoxifen is restricted to the specific patient under the FDA Expanded Access IND program.
