Antares Pharma, Inc. recently announced the approval of Xyosted (testosterone enanthate) injection by the U.S. Food and Drug Administration (FDA). Xyosted is the first FDA approved subcutaneous testosterone enanthate product for once-weekly, at-home self-administration with an easy-to-use, single dose, disposable QuickShot® auto injector. Xyosted has been approved in three dosage strengths, 50 mg, 75 mg and 100 mg and is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone.

"Today's FDA approval of Xyosted is a significant milestone for Antares. Xyosted expands our branded portfolio of combination drug/device products and continues to highlight our passion and commitment to providing high quality therapies that improve patient care," said Robert F. Apple, President and Chief Executive Officer of the Company. "Xyosted, the first subcutaneous auto injector product designed for testosterone replacement therapy will soon be available for adult males diagnosed with a deficiency or absence of endogenous testosterone.

Published data from the Xyosted phase three studies have shown our product to be easy to use and virtually pain free while providing steady testosterone levels." He concluded, "We believe Xyosted significantly enhances a testosterone deficient patient's option for treatment, and I am proud of our team's success in developing and bringing to market this novel product. We will now begin the process of onboarding sales representatives and expect to make Xyosted available to patients before the end of this year."

Jed C. Kaminetsky, MD, a urologist at University Urology Associates, Medical Director of Manhattan Medical Research, clinical assistant professor of urology at New York University School of Medicine and principal investigator in the Xyosted pivotal studies said, "A once-weekly, at-home, subcutaneously administered testosterone product represents an exciting new treatment option for men suffering from hypogonadism." He continued, "The subcutaneous dosing of Xyosted also removes transfer concerns commonly associated with gels and potentially reduces the need for in-office injection procedures that may require more frequent patient visits. Xyosted has been clinically shown to produce physiologically normal levels of testosterone with a narrow peak-to-trough ratio."

Xyosted enters the testosterone replacement therapy market where approximately 6.5 million retail prescriptions were filled in 2017, according to data from Symphony Health Solutions. The majority of the prescriptions written were for injectable (66%) and topical (32%) testosterone products.

Important safety information

Xyosted can cause blood pressure increases that can increase the risk for major adverse cardiovascular events (MACE), including non-fatal myocardial infarction, non-fatal stroke and cardiovascular death, with greater risk for MACE in patients with cardiovascular risk factors or established cardiovascular disease.

Before initiating Xyosted, consider the patient's baseline cardiovascular risk and ensure blood pressure is adequately controlled.

Starting approximately 6 weeks after initiating therapy, periodically monitor for and treat new-onset hypertension or exacerbations of pre-existing hypertension in patients on Xyosted.

Re-evaluate whether the benefits of Xyosted outweigh its risks in patients who develop cardiovascular risk factors or cardiovascular disease while on treatment.

Due to this risk, use Xyosted only for the treatment of men with hypogonadal conditions associated with structural or genetic etiologies.

Indications and usage

Xyosted (testosterone enanthate) injection is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone.

Primary hypogonadism (congenital or acquired)

Hypogonadotropic hypogonadism (congenital or acquired)

Iimitations of use

Safety and efficacy of Xyosted in men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established

Safety and efficacy of Xyosted in males less than 18 years old have not been established

Contraindications

Xyosted is contraindicated in:

Men with carcinoma of the breast or known or suspected carcinoma of the prostate.

Women who are pregnant. Testosterone can cause virilization of the female fetus when administered to a pregnant woman.

Men with known hypersensitivity to Xyosted or any of its ingredients (testosterone enanthate and sesame oil).

Men with hypogonadal conditions, such as "age-related hypogonadism", that are not associated with structural or genetic etiologies. The efficacy of Xyosted has not been established for these conditions, and Xyosted can increase blood pressure (BP) that can increase the risk of MACE.

Use in specific populations

Pregnancy—Xyosted is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action. Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies.

Lactation—Xyosted is not indicated for use in females.

Females and Males of Reproductive Potential - During treatment with large doses of exogenous androgens, including Xyosted, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis. Reduced fertility is observed in some men taking testosterone replacement therapy. The impact on fertility may be irreversible.

Pediatric Use—Safety and effectiveness of Xyosted in pediatric patients less than 18 years old have not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.

Geriatric Use—There have not been sufficient numbers of geriatric patients in controlled clinical studies with Xyosted to determine whether efficacy or safety in those over 65 years of age differs from younger subjects. Of the 283 patients enrolled in the 6-month and 1-year efficacy and safety clinical study utilizing Xyosted, 49 (17%) were over 65 years of age. Additionally, there are insufficient long-term safety data in geriatric patients to assess the potentially increased risk of cardiovascular disease and prostate cancer. Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH.