ANI Pharmaceuticals (ANIP)

[Just the facts maam]

Several takeaways from the Clinical Practice Guidelines for Systemic Testosterone Use for Women.

By 2030, using the age of 50 years as a proxy for menopause, the world population of postmenopausal women will be around 1.2 billion, with an incidence of 47 million reaching menopause each year.

A phase 3 cardiovascular and breast safety RCT of 1% testosterone transdermal gel, 300 mcg daily was undertaken in 2008 and enrolled 3,656 postmenopausal participants older than 50 years, with at least 2 cardiovascular risk factors at baseline (eg, hypertension, dyslipidemia) and a clinical diagnosis of HSDD.115 The composite cardiovascular end point included death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, hospitalized unstable angina, and venous thromboembolic events.115 After 4 years, with more than 7,300 women-years of exposure, the company (BioSante Pharmaceuticals, Inc) reported 53 adjudicated cardiovascular events, a lower than anticipated rate, with the number of breast cancers as anticipated based on subject ages.116 Study results have been published in press releases but not in peer-reviewed publications.

Future Strategies to Assess Safety
Several recent meta-analyses and the 4-year open-label extension trial provide safety reassurance for the use of transdermal testosterone therapy in postmenopausal women with doses that approximate physiological levels for premenopausal women.114 However, reported RCTs to date have neither been large enough nor long enough to definitively determine the effects of testosterone therapy on safety outcomes of interest: cardiovascular events, breast cancer risk, endometrial and ovarian effects, cognitive health, mood, and musculoskeletal health.

One interim approach would be to establish longitudinal observational studies and patient registries to supplement completed RCTs. It would be clinically useful to stratify safety data by menopausal status, ovarian status (intact vs oophorectomized), and concurrent estrogen and progestogen therapies. As with studies of estrogen and progestin therapies, reassurances of safety would be strengthened with stratification of cardiovascular outcomes (venous thromboembolic events, stroke, myocardial infarction), by age, time since menopause, and metabolic characteristics to facilitate advising women at different baseline risk.

If a deal is in place, I can see peer review articles including Libigel's data coming in 2022.