Lipocine Withdraws Preliminary Injunction Threat Against Marketing of Clarus Therapeutics’ JATENZO® Product: Trial Date Set for August 2020


NORTHBROOK, Ill., Aug. 26, 2019 (GLOBE NEWSWIRE) -- Clarus today announced that Lipocine, Inc. has confirmed that it will not seek preliminary injunctive relief against Clarus in a lawsuit that asserts Clarus’s product JATENZO infringes certain Lipocine patents -- even in the event that Clarus launches JATENZO (oral testosterone undecanoate capsules for the treatment of appropriate men with testosterone deficiency).  A trial date in the dispute between Clarus and Lipocine has been set for August 24, 2020 in the United States District Court for the District of Delaware.

“We remain confident that we will prevail in the litigation with Lipocine and appreciate the Court’s scheduling of the trial on a much faster track than is often the case for disputes of this nature,” said Dr. Robert E. Dudley, President and Chief Executive Officer of Clarus.  “We are continuing our efforts to make our innovative JATENZO product available as soon as possible for use by appropriate men who have a testosterone deficiency.” For full JATENZO prescribing information please visit: www.JATENZO.com.

About Clarus Therapeutics

Clarus is a men's specialty pharmaceutical company developing and preparing for the commercial launch of JATENZO, a product protected by patents issued in the United States and in other major pharmaceutical markets around the world. Clarus owns the worldwide, royalty-free commercialization rights for JATENZO.  For more information, please visit: www.clarustherapeutics.com

IMPORTANT SAFETY INFORMATION

JATENZO™ (testosterone undecanoate) capsules, for oral use CIII

Initial US approval: 1953


WARNING: BLOOD PRESSURE INCREASES
  • JATENZO 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 JATENZO, consider the patient’s baseline cardiovascular risk and ensure blood pressure is adequately controlled.
  • Starting approximately 3 weeks after initiating therapy or changing the dose, periodically monitor for and treat new-onset hypertension or exacerbations of pre-existing hypertension in patients on JATENZO.
  • Re-evaluate whether the benefits of JATENZO outweigh its risks in patients who develop cardiovascular risk factors or cardiovascular disease while on treatment.
  • Due to this risk, use JATENZO only for the treatment of men with hypogonadal conditions associated with structural or genetic etiologies.

JATENZO INDICATIONS AND USAGE

JATENZO (testosterone undecanoate) 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)

LIMITATIONS OF USE

  • Safety and efficacy 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 efficacy 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 intensification 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 benefits 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 efficacy of JATENZO has not been established for these conditions and the increases in BP can increase the risk of MACE.

Polycythemia—Increases in hematocrit reflective 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 profile may require dose adjustment of lipid lowering drugs or discontinuation of testosterone therapy. Monitor the lipid profile 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 fluid 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 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. No patients over 65 years of age were enrolled in the 4-month efficacy and safety clinical study utilizing JATENZO.  Additionally, there is insufficient 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 defined 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.


            

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