SEATTLE—Clinical-stage biopharmaceutical company Atossa Genetics Inc. has reported successful final results from its Phase 1 dose-escalation study of its proprietary topical Endoxifen in 24 healthy male subjects at various dose levels over 28 days, passing with flying colors in all three major areas: safety, tolerability and pharmacokinetics. The study was conducted on behalf of Atossa by Australia-based CPR Pharma Services Pty Ltd.
The study found no clinically significant safety signals and no clinically significant adverse events in participants receiving topical Endoxifen. In terms of tolerability, topical Endoxifen was well tolerated at each dose level and for the dosing duration utilized in the study; in pharmacokinetics, blood samples showed no measurable Endoxifen.
“These positive final results support the further development of topical Endoxifen to treat breast health conditions in men, including a condition called gynecomastia—or breast enlargement and pain—which frequently occurs in men taking androgen-deprivation therapy for prostate cancer,” says Dr. Steven C. Quay, Atossa CEO and president.
“We are also conducting a Phase 2 study using our topical Endoxifen in women with mammographic breast density (MBD), which we anticipate completing in the second quarter 2019,” Quay adds. “Once we have the results from the MBD study, we will determine next steps using topical Endoxifen to treat male breast conditions including gynecomastia, which, according to the Mayo Clinic, affects 25 percent of men in the U.S. between the ages of 50 to 69, or approximately 10 million men.”
Gynecomastia is the most common male breast disorder and is caused by a hormone imbalance where testosterone levels are lower than estrogen. Gynecomastia is caused by, among other things, any number of commonly prescribed medications, such as androgen-deprivation therapy to treat prostate enlargement and prostate cancer, anti-anxiety medications, cancer treatments (chemotherapy) and some heart medications.
Not only is it painful and embarrassing, gynecomastia can also be the reason some men stop taking their prescribed medication, Quay says. In prostate cancer treatment, for instance, testosterone is suppressed, resulting in higher estrogen levels that often trigger gynecomastia.
Since there is no FDA-approved pharmaceutical to treat gynecomastia, current approaches in these patients include pain control and prophylactic breast bud irradiation, which is often repeated. Some patients opt for breast reduction surgery, according to Atossa. Gynecomastia can also create quality of life issues, with some patients attempting to hide the condition with compression garments.
“We believe, subject to further clinical studies and regulatory approval, that our topical Endoxifen could fill a significant unmet medical need in reducing the risk of gynecomastia in men taking certain therapies to treat prostate cancer and helping them maintain their quality of life,” Quay states.
Due to more awareness of MBD in women, legislation has been recently enacted in over 30 states requiring women be notified if they have MBD, Atossa reports. These notifications typically state that women with MBD have a higher risk of developing breast cancer, and that mammography may not be as effective in detecting breast cancer because the MBD can “mask” the detection of cancers.
“We estimate that approximately 10 million women in the U.S. have MBD, for which there is no FDA-approved treatment,” Quay notes. “Although oral Tamoxifen is approved to prevent breast cancer in ‘high-risk’ women, it is used by less than 5 percent of women with an increased risk of developing breast cancer because of the actual or perceived side effects and risks of Tamoxifen.”
Atossa is conducting a double-blinded, placebo-controlled Phase 2 study in women with MBD at Stockholm South General Hospital in Sweden using its topical Endoxifen, led by principal investigator Dr. Per Hall, head of the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Stockholm.
The primary endpoint is to determine if daily topical Endoxifen administration results in an individual change in MBD, which will be measured after three and six months of entering the study.
The secondary endpoints are safety and tolerability, Quay says. Ninety participants were randomized to one of three groups (one placebo group and two groups of different strengths of topical Endoxifen), with about 30 participants per group.
The objective of the study is to determine if MBD is reduced, and if so, the results will drive sample size calculations for a future Phase 3 study.