Sometimes called “compassionate use,” expanded access is a potential pathway for a patient with serious disease or condition, or an immediately life-threatening condition, to gain access to an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.
Today, Seattle-based Atossa Genetics Inc. (NASDAQ: ATOS), a clinical-stage biopharmaceutical company developing novel therapeutics and delivery methods to treat breast cancer and other breast conditions, announced that the FDA has issued a “Safe to Proceed” letter under their “expanded access” program permitting the use of Atossa’s oral Endoxifen as a post-mastectomy treatment in a pre-menopausal, estrogen-receptor positive (ER+) breast cancer patient. This patient completed a 3-week course of Atossa’s oral Endoxifen prior to her surgery under an FDA-approved expanded access program.
Shares of Atossa Genetics (NASDAQ: ATOS) are currently trading up over 239% at $5.13 today after hitting a intraday high of $5.69. The 52-week trading range is $.80 – $7.56.
The tumor activity from the initial biopsy was compared to the tumor activity at surgery, finding that the cancer cell biological activity was reduced by two measures: the Ki-67 activity decreased by 50 percent, and the estrogen receptor content decreased by over 20 percent. There were no safety or tolerability issues, including vasomotor symptoms such as hot flashes and night sweats. The latter symptoms are often a tolerability challenge for patients on tamoxifen.
Dr. Steven C. Quay, President and CEO of Atossa stated, “We are extremely pleased that this patient not only benefitted from Endoxifen prior to her surgery but that the FDA agrees that continued Endoxifen therapy is appropriate for this pre-menopausal patient. This positive progress supports our expansion of oral Endoxifen clinical trials. After the surgery is completed, the current standard of care in the USA to prevent a recurrence and/or a new cancer is for patients to undergo ovarian ablation (chemical treatment to induce menopause) and take aromatase inhibitors (AI) for 5 to 10 years. Alternatively, tamoxifen therapy can be used for 5-10 years for those patients who do not want to take AIs, or for whom these medications are contraindicated. This patient, like many others, was not a good candidate for tamoxifen therapy due to low liver enzyme (CYP2D6) activity which means her liver would not adequately metabolize tamoxifen. Unlike tamoxifen, oral Endoxifen does not require liver metabolism so it may be a better treatment approach.”
The importance of Ki-67 as a marker of estrogen-receptor breast cancer cell activity has evolved over the past few years. In a 2017 peer-reviewed paper1 in which a meta-analysis was conducted and included 49 studies and 14,046 patients, five studies reported and compared the change of Ki-67 following pre-surgery hormonal therapy treatment and the disease-free survival (DFS). The authors reported that from their analysis, a Ki-67 change that is either low or none, as well as an increase, is associated with worse DFS. The reduction of Ki-67 in the tumor of the patient who received oral Endoxifen prior to her mastectomy is considered large, based on the criteria of this paper.
Under the FDA expanded access IND program, the use of Atossa’s proprietary oral Endoxifen is restricted solely to this patient. Approval from the Institutional Review Board (IRB) must be obtained prior to providing oral Endoxifen to this patient.
Endoxifen is an active metabolite of tamoxifen, which is an FDA-approved drug to prevent new as well as recurrent disease in breast cancer patients. Tamoxifen itself must be broken down by the liver into active compounds (metabolites), of which Endoxifen is the most active. Studies by others have shown that breast cancer patients with endoxifen levels of 30 nM and above have a lower risk for developing future breast cancer. Up to half of the patients taking tamoxifen do not produce therapeutic levels of endoxifen, frequently because of limited liver metabolism capability.
Studies by others indicate that endoxifen’s molecular mechanisms of action are concentration dependent and different than that of other anti-estrogens, including fulvestrant. Pathway analysis of differentially regulated genes revealed substantial differences related to endoxifen concentrations including significant induction of cell cycle arrest and markers of apoptosis following treatment with high, but not low, concentrations of endoxifen.
Many patients taking tamoxifen eventually stop responding, becoming tamoxifen refractory. In a small study by others of oral endoxifen use by tamoxifen refractory patients, endoxifen provided an acceptable safety profile and promising antitumor activity. Another class of drugs called aromatase inhibitors are also frequently used to treat breast cancer; however, they are not FDA-approved for use in pre-menopausal women and can only be given to pre-menopausal women in conjunction with drugs for ovarian suppression/oblation, which can cause cardiovascular and other toxicities. Additionally, 20-30 percent of those taking aromatase inhibitors may experience fractures, bone pain or osteoporosis. Because of these potential advantages, Atossa is developing oral and topical forms of Endoxifen.
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Atossa Genetics Announces FDA Approval of Oral Endoxifen for “Expanded Access” as Post-Mastectomy Treatment for a U.S. Breast Cancer Patient
Atossa Genetics Inc. (ATOS), a clinical-stage biopharmaceutical company developing novel therapeutics and delivery methods to treat breast cancer and other breast conditions, today announced that the FDA has issued a “Safe to Proceed” letter under their “expanded access” program permitting the use of..