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NORTHBROOK, Ill., March 20, 2021 /PRNewswire/ -- Clarus Therapeutics Inc. announced today positive results of an open-label, multi-center safety and efficacy analysis following two years of JATENZO^® (testosterone undecanoate) oral capsules use in hypogonadal men. The data — presented virtually at ENDO 2021, the Endocrine Society's annual meeting — supports JATENZO as an effective long-term testosterone replacement therapy (TRT), with no evidence of liver toxicity.^1,2 JATENZO, which was approved in March 2019 and made commercially available in February 2020, is the first and only FDA-approved oral softgel for TRT in adult males who have low or no testosterone due to certain medical conditions. ^3,4

"Prior to the launch of JATENZO, the only approved oral TRT formulation in the U.S. — methyl-testosterone (alkylated androgen) — was associated with significant liver toxicity," said Ronald S. Swerdloff, MD, MACP, lead study author and senior investigator at the Lundquist Institute at Harbor-UCLA. "These results are significant because they provide adult men with hypogonadism an oral option that is not only effective in maintaining normal testosterone levels, but also has no evidence of damage to the liver."

The two-part study evaluated two years of twice-daily JATENZO use in hypogonadal men (two serum T ≤ 300 ng/dL) aged 18-75 years. The first study followed patients for 12 months; 86 men from the first study then enrolled in the second study, which lasted another year. The analysis found that JATENZO use^1,2:

• Kept total testosterone levels in the normal range with a safety profile that is relatively consistent with other forms of TRT. ^1,2
• Demonstrated no clinically significant change in liver function tests – no clinically significant changes in alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminases (ALT), and bilirubin levels. ^1,2
• Showed small, yet statistically significant, increases in prostate-specific antigen (PSA), a protein produced by the prostate, and hematocrit (HCT), which measures red blood cell levels. These increases are observed with other TRTs, regardless of mode of administration. ^1,2
• Had minimal effects on LDL ("bad") cholesterol and lowered HDL ("good") cholesterol, which is common among other TRTs. ^1,2

"We launched JATENZO to provide men with low testosterone an effective oral option that avoids some of the drawbacks of other routes of administration, such as injection-site pain or testosterone transference to partners and children, without harmful effects on the liver," said Dr. Bob Dudley, chairman, CEO and president of Clarus Therapeutics. "We're thrilled with these long-term results that continue to show we achieved that goal, and that JATENZO can offer a long-term therapeutic benefit for many patients."

The primary efficacy variable in the analysis was the change from baseline of total testosterone (T). The key safety variables included change in blood pressure (BP), including both systolic and diastolic BP; HCT, prostate variables, such as PSA and prostate function, via The American Urological Association International Prostate Symptom Score (AUA-IPSS); and liver function tests, including ALP, AST, ALT, and bilirubin.^1,2

For more information on JATENZO, visit JATENZO.com.

About Hypogonadism
Hypogonadism is a clinical syndrome that results from a failure of the testes to produce physiological concentrations of testosterone.⁵ According to current clinical guidelines from the Endocrine Society and the American Urological Association, diagnosis of hypogonadism is determined by both the identification of symptoms and/or signs consistent with the condition, and measurement of low morning total serum testosterone concentration, defined as <300 ng/dL, on 2 separate days.^4,6

About JATENZO
JATENZO is the first and only FDA-approved oral testosterone undecanoate for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired).^2,3

JATENZO's proprietary formulation is built around testosterone undecanoate—a testosterone prodrug that the body converts to testosterone.^2,3 In the JATENZO pivotal inTUne (investigational testosterone undecanoate) clinical trial, 87 percent of hypogonadal men treated with JATENZO achieved a mean total testosterone concentration in the eugonadal range at the end of treatment.⁷ The efficacy and safety of JATENZO was evaluated in 166 adult, hypogonadal males in a 4-month, open-label study. The primary endpoint was the percentage of patients with mean plasma total testosterone concentration (C_avg) over 24 hours within the normal eugonadal range on the final PK visit of the study.²

About Clarus Therapeutics, Inc.
Clarus is a specialty pharmaceutical company whose first commercial product, JATENZO, was launched in early 2020. For more information, visit www.clarustherapeutics.com.

Indication
JATENZO^® (testosterone undecanoate) capsules, CIII, 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): testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.
• Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range.

Limitation of use
Safety and efficacy of JATENZO in males less than 18 years old have not been established.

IMPORTANT SAFETY INFORMATION

WARNING: INCREASES IN BLOOD PRESSURE

• JATENZO can cause blood pressure (BP) increases that can increase the risk of major adverse cardiovascular events (MACE), including non-fatal myocardial infarction, non-fatal stroke and cardiovascular death.
• Before initiating JATENZO, consider the patient's baseline cardiovascular risk and ensure blood pressure is adequately controlled.
• Periodically monitor for and treat new-onset hypertension or exacerbations of pre-existing hypertension and re-evaluate whether the benefits of JATENZO outweigh its risks in patients who develop cardiovascular risk factors or cardiovascular disease on treatment.
• Due to this risk, use JATENZO only for the treatment of men with hypogonadal conditions associated with structural or genetic etiologies.

CONTRAINDICATIONS
JATENZO is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate, in women who are pregnant, in men with a known hypersensitivity to JATENZO or its ingredients, or in men with hypogonadal conditions that are not associated with structural or genetic etiologies as JATENZO has not been established for these conditions and there is a risk of increased blood pressure with JATENZO that can increase the risk of MACE.

WARNINGS AND PRECAUTIONS

• JATENZO can increase blood pressure, which can increase the risk of MACE, with greater risk in patients with established cardiovascular disease or risk factors for cardiovascular disease. Before initiating JATENZO, consider the patient's baseline cardiovascular risk and ensure blood pressure is adequately controlled. Monitor blood pressure approximately 3 weeks after initiating, increasing the dose, and periodically while on JATENZO, and treat any new or exacerbations of hypertension. Re-evaluate benefits and risks of continued treatment with JATENZO in patients who develop cardiovascular risk factors or disease. JATENZO is contraindicated in men with hypogonadal conditions such as "age-related hypogonadism" because the efficacy of JATENZO has not been established for these conditions and the increases in BP can increase the risk of MACE.
• Polycythemia may require a lower dose or discontinuation of JATENZO. Check hematocrit prior to initiation and every 3 months while a patient is on JATENZO and if hematocrit becomes elevated, stop JATENZO until hematocrit decreases to an acceptable level. If hematocrit increases after JATENZO is restarted, stop permanently.
• Some studies, but not all, have reported an increased risk of major adverse cardiovascular events (MACE) in association with use of testosterone replacement therapy in men. Long-term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use JATENZO. JATENZO can increase blood pressure, which can increase the risk of MACE.
• Monitor patients with benign prostatic hyperplasia (BPH) treated with androgens due to an increased risk for worsening signs and symptoms of BPH. Patients treated with androgens may be at increased risk for prostate cancer and should be evaluated prior to initiating and during treatment with androgens. Monitor prostate-specific antigen (PSA) levels periodically.
• Postmarketing reports of venous thromboembolic events (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), have been reported in patients using testosterone replacement products like JATENZO. Evaluate patients with signs or symptoms consistent with DVT or PE and, if a VTE is suspected, discontinue JATENZO and initiate appropriate workup and management.
• Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions. If abuse is suspected, check testosterone levels to ensure they are in therapeutic range. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.
• JATENZO is not indicated for use in women.
• Large doses of androgens can suppress spermatogenesis by feedback inhibition of pituitary FSH. Inform patients of this risk before prescribing JATENZO.
• Prolonged use of high doses of methyltestosterone has been associated with serious hepatic adverse events. JATENZO is not known to cause these adverse events; however, patients should be instructed to report any signs of hepatic dysfunction and JATENZO should be discontinued while the cause is evaluated.
• Androgens, including JATENZO, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required.
• Gynecomastia may develop and persist in patients being treated for hypogonadism.
• The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung disease.
• Changes in the serum lipid profile may require dose adjustment of lipid-lowering drugs or discontinuation of testosterone therapy. Monitor the lipid profile periodically, particularly after starting testosterone therapy.
• Use JATENZO with caution in cancer patients at risk of hypercalcemia. Monitor serum calcium concentration regularly during treatment with JATENZO in these patients.
• Androgens, including JATENZO, may decrease concentrations of thyroxine-binding globulin, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.
• Depression and suicidal ideation have been reported in patients treated with JATENZO in clinical trials. Advise patients and caregivers to seek medical attention for manifestations of new-onset or worsening depression, suicidal ideation or behavior, anxiety, or other mood changes.

ADVERSE EVENTS
The most common adverse events of JATENZO (incidence ≥2%) are headache (5%), increased hematocrit (5%), hypertension (4%), decreased HDL (3%), and nausea (2%).

DRUG INTERACTIONS

• JATENZO can cause changes in insulin sensitivity or glycemic control. Androgens may decrease blood glucose and may require a decrease in the dose of antidiabetic medications.
• Anticoagulant activity may be affected by androgens. More frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking warfarin, especially at initiation and termination of androgen therapy.
• Use of testosterone and corticosteroids concurrently may increase fluid retention and requires monitoring in patients with cardiac, renal, or hepatic disease.
• Some prescription and nonprescription analgesic cold medications contain drugs known to increase blood pressure and concomitant use of these medications with JATENZO may lead to additional increases in blood pressure.

USE IN SPECIFIC POPULATIONS
The safety and efficacy of JATENZO 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.

There have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing JATENZO to determine whether efficacy or safety in those over 65 years of age differs from younger subjects. There is insufficient long-term safety data in geriatric patients utilizing JATENZO to assess the potentially increased risk of cardiovascular disease and prostate cancer.

Please click here for full Prescribing Information, including BOXED WARNING on increases in blood pressure.

© 2020 Clarus Therapeutics, Inc. All rights reserved.

¹ Swerdloff R, et al. Safety Analysis of an Oral Testosterone Undecanoate (TU) Formulation Following 2 Years of Administration in Hypogonadal Men. Poster presented at: ENDO 2021; March 20, 2021; Virtual. Accessed March 11, 2021.
² Swerdloff R, et al. Ther Adv Urol. 2020;12:1-16. (part 1)
³ JATENZO (testosterone undecanoate) [prescribing information]. Clarus Therapeutics, Inc.
⁴ US Food & Drug Administration. FDA Approved Drug Products. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=206089. Accessed October 1, 2019.
⁵ Bhasin S, et al. J Clin Endocrinol Metab. 2018;103(5):1715-1744.
⁶ Mulhall JP, et al. J Urol. 2018;200(2):423-432.
⁷ Swerdloff et al., J Clin Endocrinol Metab 2020;105:2515-31.

SOURCE Clarus Therapeutics Inc.