Clarus Therapeutics Receives U.S. FDA Approval of JATENZO® (Testosterone Undecanoate Capsules for Oral Use) (CIII) for Testosterone Replacement Therapy in Certain Adult Men

Mar  2019

JATENZO is a rst-in-class proprietary softgel oral formulation of testosterone undecanoate for testosterone replacement therapy in certain adult men

NORTHBROOK,  Ill., March 27, 2019 (GLOBE NEWSWIRE)  -- Clarus Therapeutics, Inc., today announced that the U.S. Food and Drug Administration (FDA) has  approved JATENZO® (testosterone undecanoate capsules for oral use)  (CIII) for testosterone replacement therapy in adult males for conditions associated with a deciency or

absence of endogenous testosterone: primary hypogonadism (congenital or acquired)

and hypogonadotropic hypogonadism (congenital or acquired). Important Safety

Information, including a Boxed Warning is provided  below.


JATENZO is a rst-in-class proprietary softgel oral formulation, and the rst oral testosterone medicine approved in more than 60 years.1  FDA approval is based on Phase 3 inTUne clinical trial data, which showed 87 percent of hypogonadal men treated with JATENZO achieved a daily average testosterone level in the normal  range, with an adverse events prole generally  consistent with other T replacement therapies.


“The approval of oral JATENZO represents a new and signicant treatment option  for hypogonadal men,” said Dr. Robert E. Dudley, President and Chief Executive Ocer of Clarus. “We believe that an oral testosterone replacement therapy may offer appropriate adult male patients and their physicians the opportunity to reconsider treatment options, and help hypogonadal men nd relief from their symptoms.”


Patient adherence can be an issue with testosterone treatment. The oral delivery of JATENZO eliminates the risks of testosterone transference to women or children that can occur  with gels, application site irritation common with the transdermal testosterone patch,  and discomfort associated with deep  muscle injections of testosterone formulations. JATENZO is an important addition to the class of drugs used to treat  various  forms of testosterone deciency.


“JATENZO will ll an important void by providing physicians with an oral testosterone formulation FDA has  found to be safe and effective to treat  adult men with documented hypogonadism associated with structural or genetic etiologies,” said Dr. Ronald Swerdloff, Distinguished Professor of Medicine  at the David Geffen School  of Medicine at UCLA, Senior Scientist at the Los Angeles  Biomedical Research Institute and

Principal  Investigator for the JATENZO clinical trials. “Availability of a safe and effective oral testosterone dosage form has  long been  a desire of many of my hypogonadal patients.”


JATENZO will be available in three  dosages: 158 mg, 198 mg and 237 mg, for twice daily administration with food. Clarus expects JATENZO to be available in U.S. pharmacies before the end of the year.


"We represent thousands of men who struggle to maintain adequate levels of testosterone, many of whom do not start or stay on testosterone therapy because of issues with the current formulations," said Carol Meerschaert, Executive Director of the Association for X and Y Variations (AXYS), an advocacy, education and support organization for individuals  with X and Y chromosome variations and their families. "An oral testosterone medication, which AXYS has  supported since early trials were rst announced, could make  a signicant difference in their physical  and mental well-being and we hope  will help them  to lead fuller, more productive lives."


JATENZO is not for use  in men with hypogonadal conditions, such  as “age-related hypogonadism,” that are not associated with structural or genetic etiologies. Please

see  Important Safety Information below, including Boxed Warning for information about potential increased blood pressure associated with JATENZO.


About the inTUne Trial


The inTUne trial was a multicenter, randomized, open-label, study  designed to evaluate the ecacy  and safety of JATENZO in adult hypogonadal male subjects. An active comparator group received Axiron®, a topical  testosterone formulation. A total of 222 patients were randomized in a 3:1 ratio to JATENZO (n=166) or Axiron (n=56). The primary ecacy  endpoint was the percentage of patients in the JATENZO group with an average testosterone level in the normal  male range.


Both the percentage of patients (87.3%) and the lower bound  of the 95% condence interval (81.3%) met the FDA targets of ≥ 75% and ≥ 65%, respectively; therefore, the ecacy  criteria were satised and the study  met its primary endpoint. The safety prole of JATENZO was consistent with data  generated in two earlier Phase 3 trials and the general safety proles  for T replacement products as a therapeutic class.  JATENZO was associated with an increase in average systolic blood pressure consistent with a currently marketed form of injectable testosterone.  Importantly, the inTUne trial conrmed the ecacy  of JATENZO that was demonstrated in the earlier Phase 3 trials but further  rened  the dose adjustment scheme.


About Hypogonadism


Hypogonadism, also  known as testosterone deciency, is a condition in men in which the body does not produce enough testosterone. Only those men who are symptomatic and have consistently low results on a reliable testosterone assay should be offered testosterone replacement therapy, according to current treatment guidelines from both

the Endocrine Society and the American Urological Association.2,3 Treatment is meant to induce  and maintain secondary sex characteristics and improve bone  mineral density, sexual function,  sense of well-being, muscle mass and strength. In 2018,

approximately 7 million testosterone replacement therapy prescriptions were written by healthcare providers,  with estimated total sales of $1.6 billion.4


About Clarus Therapeutics


Clarus is a men's specialty pharmaceutical company developing and preparing for the commercial launch  of JATENZO, a rst-in-class proprietary softgel oral formulation of testosterone undecanoate for testosterone replacement therapy in certain adult males protected by patents issued in the United States and in other major pharmaceutical markets around the world. JATENZO is the rst oral testosterone prodrug  FDA- approved to treat  men diagnosed with hypogonadism associated with structural and genetic etiologies. Clarus owns  the worldwide, royalty-free commercialization rights  for JATENZO. For more information, please visit: www.clarustherapeutics.com


For full prescribing information please visit WWW.JATENZO.COM


IMPORTANT SAFETY INFORMATION JATENZO™ (testosterone undecanoate) capsules, for oral use CIII Initial US approval:  1953


JATENZO INDICATIONS AND USAGE


JATENZO (testosterone undecanoate) is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deciency or absence of endogenous testosterone.


Primary hypogonadism (congenital or acquired) Hypogonadotropic hypogonadism (congenital or acquired)


LIMITATIONS OF USE


Safety and ecacy  of JATENZO in males less  than 18 years  old have not been established


CONTRAINDICATIONS


JATENZO 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 JATENZO or any of its ingredients.


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


WARNINGS AND PRECAUTIONS


Blood Pressure Increases— In a clinical trial, JATENZO increased systolic BP during 4 months of treatment by an average of 4.9 mmHg based on ambulatory blood pressure monitoring (ABPM) and by an average of 2.8 mmHg from baseline based on blood pressure cuff measurements. Average blood pressures had not plateaued at the end of the trial. Seven percent of JATENZO-treated patients were started on antihypertensive medications or required intensication of their antihypertensive medication regimen during the 4-month trial.


BP increases can increase the risk of MACE, with greater risk in patients with established cardiovascular disease or risk factors for cardiovascular disease.


These BP increases can increase the risk of MACE, with greater risk in patients with established cardiovascular disease or risk factors for cardiovascular disease [see Boxed Warning].


In some patients, the increase in BP with JATENZO may be too small to detect, but can still increase the risk for MACE.


Before initiating JATENZO, consider the patient’s baseline cardiovascular risk and ensure blood pressure is adequately controlled. Check BP approximately 3 weeks after initiating JATENZO or increasing the dose and periodically  thereafter. Treat new-onset hypertension or exacerbations of pre-existing hypertension. Re-evaluate whether the benets of continued treatment with JATENZO outweigh its risks in patients who develop cardiovascular risk factors or cardiovascular disease.


JATENZO is contraindicated in men with hypogonadal conditions such  as “age-related hypogonadism,” because the ecacy  of JATENZO has  not been  established for these conditions and the increases in BP can increase the risk of MACE.


Polycythemia— Increases in hematocrit reective of increases in red blood cell mass, may require  lowering the dose or discontinuation of JATENZO. Check that hematocrit is not elevated prior to initiating JATENZO. Evaluate  hematocrit approximately every 3 months while the patient is on JATENZO. If hematocrit becomes elevated, stop JATENZO until the hematocrit decreases to an acceptable concentration. If JATENZO is restarted and again  causes hematocrit to become elevated, stop JATENZO

permanently. An increase in red blood cell mass may increase the risk of thromboembolic events.


Cardiovascular Risk— Long term clinical safety trials have not been  conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been  inconclusive for determining the risk of MACE, such  as non-fatal myocardial infarction,  non-fatal stroke,  and cardiovascular death,  with the use  of testosterone compared to non-use. Some  studies, but not all, have reported an increased risk of MACE in association with use  of testosterone replacement therapy in men.


JATENZO can cause BP increases that can increase the risk of MACE [see Boxed Warning and Warnings  and Precautions (5.1)]. Patients should be informed of this possible risk when deciding whether to use  or to continue to use  JATENZO.


Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer— Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms.


Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens.


Venous Thromboembolism (VTE)— There have been  postmarketing reports of venous thromboembolic events, including deep  vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone replacement products such  as JATENZO. Evaluate  patients who report  symptoms of pain, edema, warmth and erythema in the lower extremity  for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with JATENZO

and initiate appropriate workup and management.


Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations— 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 testosterone abuse is suspected, check  testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal  or subnormal range  in men abusing synthetic testosterone derivatives. 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.


Not for Use in Women— Due to lack of controlled studies in women and potential virilizing effects, JATENZO is not indicated for use  in women.


Potential for Adverse Effects on Spermatogenesis— With large doses of exogenous androgens, including JATENZO, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count.  Patients should be informed of this possible risk when deciding whether to use  or to continue to use JATENZO.


Hepatic Adverse Effects— Prolonged use  of high doses of orally active  17-alpha-alkyl androgens (e.g., methyltestosterone) has  been  associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term  therapy with intramuscular testosterone enanthate, which elevates blood levels for prolonged periods, has  produced multiple hepatic adenomas. JATENZO is not known to produce these adverse effects. Nonetheless, patients should be instructed to report  any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly  discontinue JATENZO while the cause is evaluated.


Edema— 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 preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic  therapy may be required.


Gynecomastia— Gynecomastia may develop  and may persist in patients being treated for hypogonadism.


Sleep Apnea— Treatment with testosterone products, including JATENZO, may potentiate sleep apnea in some patients, especially those with risk factors such  as obesity or chronic  lung disease.


Lipids— Changes in the serum lipid prole may require  dose adjustment of lipid lowering drugs  or discontinuation of testosterone therapy. Monitor the lipid prole periodically, particularly  after starting testosterone therapy.


Hypercalcemia— Androgens, including JATENZO, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Monitor serum calcium concentrations regularly during treatment with JATENZO in these patients.


Decreased Thyroxine-binding Globulin— 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.


Risk of Depression and Suicide— Depression and suicidal ideation has  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 REACTIONS

The safety of JATENZO was evaluated in a randomized, controlled clinical study  with

166 patients treated with JATENZO twice daily with morning  and evening  meals for approximately 4 months. All patients were started on 237 mg twice daily, then the dose was titrated to 158 mg, 198 mg, 316 mg, or 396 mg twice daily to achieve testosterone concentrations in the eugonadal range.


The most commonly reported adverse reactions (>2%) were: increased hematocrit , hypertension,, nausea, diarrhea, dyspepsia, burping, peripheral edema, enlarged prostate and headache.


DRUG INTERACTIONS


Insulin— Changes in insulin sensitivity or glycemic  control  may occur  in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of anti-diabetic medication.


Oral Anticoagulants— Changes in anticoagulant activity may be seen with androgens, therefore, more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking warfarin, especially at the initiation and termination of androgen therapy.


Corticosteroids— The concurrent use  of testosterone with corticosteroids may result  in increased uid retention and requires careful  monitoring, particularly  in patients with cardiac, renal or hepatic disease.


Medications that May Also Increase Blood Pressure— Some  prescription medications and nonprescription analgesic and cold medications contain drugs  known to increase blood pressure. Concomitant administration of these medications with JATENZO may lead to additional increases in blood pressure.


USE IN SPECIFIC POPULATIONS


Pregnancy— JATENZO 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— JATENZO is not indicated for use  in females.


Females  and Males of Reproductive Potential— During treatment with large doses of exogenous androgens, including JATENZO, 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 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.


Geriatric Use— There have not been  sucient numbers of geriatric  patients involved in controlled clinical studies utilizing JATENZO to determine whether ecacy  or safety in those over 65 years  of age differs  from younger  subjects. No patients over 65 years  of age were enrolled  in the 4-month ecacy  and safety clinical study  utilizing JATENZO. Additionally, there  is insucient long-term safety data  in geriatric  patients utilizing JATENZO 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.


DRUG ABUSE AND DEPENDENCE


JATENZO contains testosterone undecanoate, which is a Schedule III controlled substance as dened under  the Controlled  Substances Act.


Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often  in combination with other anabolic androgenic steroids, may be abused by athletes and bodybuilders.


Serious adverse reactions have been  reported in individuals  who abuse anabolic androgenic steroids, and include cardiac arrest, myocardial infarction,  hypertrophic cardiomyopathy, congestive heart  failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility, and aggression.


The following adverse reactions have been  reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemia, testicular atrophy, subfertility, and infertility.


The following adverse reactions have been  reported in women:  hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male pattern baldness, and menstrual irregularities.


The following adverse reactions have been  reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty.


Withdrawal symptoms can be experienced upon abrupt discontinuation in patients with addiction. Withdrawal symptoms include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia,  insomnia, decreased libido, and hypogonadotropic hypogonadism. Drug dependence in individuals  using approved doses for approved indications have not been  documented.


For more information, call 1-800-208-4115.


Please see  full Prescribing Information, including Boxed Warning and Medication

Guide.

© 2019 Clarus Therapeutics, Inc. All rights  reserved. MEDIA CONTACT:

Michael Beyer

312-961-2502

mbeyer@clarustherapeutics.com

info@cbridgecap.com
www.cbridgecap.com
© 2020 CBC Group. All Rights Reserved.