Vyleesi
Generic: BREMELANOTIDE
Basic Information
Manufacturer
Palatin Technologies
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
8c9607a2-5b57-4a59-b159-cf196deebdd9
Indications & Usage
1 INDICATIONS AND USAGE VYLEESI is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to: A co-existing medical or psychiatric condition, Problems with the relationship, or The effects of a medication or drug substance.
Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire.
Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner.
Limitations of Use VYLEESI is not indicated for the treatment of HSDD in postmenopausal women or in men.
VYLEESI is not indicated to enhance sexual performance.
VYLEESI is a melanocortin receptor agonist indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to: A co-existing medical or psychiatric condition, Problems with the relationship, or The effects of a medication or drug substance ( 1 ).
Limitations of Use ( 1 ): Not indicated for treatment of HSDD in postmenopausal women or in men.
Not indicated to enhance sexual performance.
Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire.
Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation or partner.
Limitations of Use VYLEESI is not indicated for the treatment of HSDD in postmenopausal women or in men.
VYLEESI is not indicated to enhance sexual performance.
VYLEESI is a melanocortin receptor agonist indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to: A co-existing medical or psychiatric condition, Problems with the relationship, or The effects of a medication or drug substance ( 1 ).
Limitations of Use ( 1 ): Not indicated for treatment of HSDD in postmenopausal women or in men.
Not indicated to enhance sexual performance.
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail elsewhere in labeling: Transient increases in blood pressure and reductions in heart rate [ see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.2 ) ] Focal hyperpigmentation [ see Warnings and Precautions ( 5.2 )] Nausea [ see Warnings and Precautions ( 5.3 ) ] Most common adverse reactions (incidence > 4%) are nausea, flushing, injection site reactions, headache, and vomiting.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Palatin Technologies at 1-800-972-5220 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The efficacy and safety of VYLEESI was studied in two identical, 24-week, randomized, double-blind, placebo-controlled trials in 1247 premenopausal women with acquired, generalized HSDD.
The age range was 19-56 years old with a mean age of 39 years old; 86% were White and 12% were Black.
Both trials also included a 52-week open-label, uncontrolled extension phase during which 684 patients received VYLEESI [ see Clinical Studies ( 14 )].
Most patients used VYLEESI two to three times per month and no more than once a week.
Serious adverse reactions were reported in 1.1% of VYLEESI-treated patients and 0.5% of placebo-treated patients.
Adverse Reactions Leading to Study Discontinuation The discontinuation rate due to adverse reactions was 18% among patients treated with VYLEESI and 2% among patients treated with placebo.
The most common adverse reactions leading to study drug discontinuation in the VYLEESI group were nausea (8%), headache (2%), vomiting (1%), flushing (1%), injection site reactions (1%), flu-like symptoms (<1%) and increased blood pressure (<1%).
Common Adverse Reactions Table 1 provides the incidence of common adverse reactions (those reported in at least 2% of patients in the VYLEESI treatment group and at an incidence that was greater than in the placebo group).
The most common adverse reactions included nausea, flushing, injection site reactions and headache.
The majority of events were reported to be mild (31%) to moderate (40%) in intensity and transient.
Table 1: Adverse Reactions Occurring in ≥ 2% of Patients in Randomized, Double-Blind Controlled Trials with VYLEESI in Premenopausal Women with HSDD a Includes injection site pain, unspecified injection site reactions, erythema, hematoma, pruritus, hemorrhage, bruising, paresthesia and hypoesthesia VYLEESI (n = 627) % Placebo (n= 620) % Nausea 40.0 1.3 Flushing 20.3 0.3 Injection site reactions a 13.2 8.4 Headache 11.3 1.9 Vomiting 4.8 0.2 Cough 3.3 1.3 Fatigue 3.2 0.5 Hot flush 2.7 0.2 Paraesthesia 2.6 0.0 Dizziness 2.2 0.5 Nasal congestion 2.1 0.5 Nausea In the pooled phase 3 placebo-controlled trials, nausea was the most common adverse reaction, reported in 40% of VYLEESI-treated patients compared to 1% of placebo-treated patients.
The median onset of nausea was within one-hour post-dose and lasted about two hours in duration.
The incidence of nausea was highest after the first VYLEESI dose (reported in 21% of patients) then declined to about 3% after subsequent doses.
Thirteen percent of VYLEESI-treated patients received an anti-emetic medication.
Overall, 8% of VYLEESI-treated patients and no placebo-treated patients prematurely discontinued the trials due to nausea.
[see Warnings and Precautions ( 5.3 )] In a phase 4, single-dose, placebo-controlled clinical study, pre-treatment with oral ondansetron (a 5-HT 3 receptor antagonist) did not reduce the incidence of nausea associated with VYLEESI treatment.
In this study, 228 healthy women were randomized (1:1) to receive 8 mg ondansetron or placebo orally 30 minutes prior to a single administration of 1.75 mg of VYLEESI given subcutaneously.
No significant difference in the incidence of VYLEESI-associated nausea was seen between the treatment groups.
Therefore, pre-treatment with oral ondansetron given 30 minutes prior to VYLEESI administration does not reduce the incidence of VYLEESI-associated nausea and is not recommended.
Treatment with ondansetron after VYLEESI administration or after the onset of nausea has not been formally studied.
Headache In the pooled phase 3 placebo-controlled trials, headache occurred at a higher incidence in VYLEESI-treated patients (11%) than placebo-treated patients (2%).
One patient experienced a headache event that was serious (intractable pain leading to hospitalization) and 1% of patients who received VYLEESI discontinued the study due to headache.
Flushing In the pooled phase 3 placebo-controlled trials, flushing occurred more frequently in VYLEESI-treated patients (20%) than placebo-treated patients (<1%).
None of the flushing events were serious and few were severe (<1%), and 1% of patients who received VYLEESI discontinued the study due to flushing.
Less Common Adverse Reactions Less common adverse reactions occurring in <2% of VYLEESI-treated patients and at an incidence greater than in the placebo group were upper abdominal pain, diarrhea, myalgia, arthralgia, pain, restless leg syndrome, rhinorrhea, increased creatine phosphokinase, blood pressure increased, pain in extremity and focal skin hyperpigmentation.
Acute hepatitis In the open-label, uncontrolled extension phase of one study, a single case of acute hepatitis was reported in a patient who had received 10 doses of VYLEESI over one year.
She presented with serum transaminases exceeding 40 times the upper limit of normal (ULN), total bilirubin 6 times the ULN, and alkaline phosphatase less than 2 times ULN.
Liver tests returned to normal 4 months after study drug discontinuation.
Because another etiology was not identified, the role of VYLEESI could not definitively be excluded.
There was no imbalance between treatment groups in serum transaminase outliers or other signals for hepatotoxicity in the clinical development program.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Palatin Technologies at 1-800-972-5220 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The efficacy and safety of VYLEESI was studied in two identical, 24-week, randomized, double-blind, placebo-controlled trials in 1247 premenopausal women with acquired, generalized HSDD.
The age range was 19-56 years old with a mean age of 39 years old; 86% were White and 12% were Black.
Both trials also included a 52-week open-label, uncontrolled extension phase during which 684 patients received VYLEESI [ see Clinical Studies ( 14 )].
Most patients used VYLEESI two to three times per month and no more than once a week.
Serious adverse reactions were reported in 1.1% of VYLEESI-treated patients and 0.5% of placebo-treated patients.
Adverse Reactions Leading to Study Discontinuation The discontinuation rate due to adverse reactions was 18% among patients treated with VYLEESI and 2% among patients treated with placebo.
The most common adverse reactions leading to study drug discontinuation in the VYLEESI group were nausea (8%), headache (2%), vomiting (1%), flushing (1%), injection site reactions (1%), flu-like symptoms (<1%) and increased blood pressure (<1%).
Common Adverse Reactions Table 1 provides the incidence of common adverse reactions (those reported in at least 2% of patients in the VYLEESI treatment group and at an incidence that was greater than in the placebo group).
The most common adverse reactions included nausea, flushing, injection site reactions and headache.
The majority of events were reported to be mild (31%) to moderate (40%) in intensity and transient.
Table 1: Adverse Reactions Occurring in ≥ 2% of Patients in Randomized, Double-Blind Controlled Trials with VYLEESI in Premenopausal Women with HSDD a Includes injection site pain, unspecified injection site reactions, erythema, hematoma, pruritus, hemorrhage, bruising, paresthesia and hypoesthesia VYLEESI (n = 627) % Placebo (n= 620) % Nausea 40.0 1.3 Flushing 20.3 0.3 Injection site reactions a 13.2 8.4 Headache 11.3 1.9 Vomiting 4.8 0.2 Cough 3.3 1.3 Fatigue 3.2 0.5 Hot flush 2.7 0.2 Paraesthesia 2.6 0.0 Dizziness 2.2 0.5 Nasal congestion 2.1 0.5 Nausea In the pooled phase 3 placebo-controlled trials, nausea was the most common adverse reaction, reported in 40% of VYLEESI-treated patients compared to 1% of placebo-treated patients.
The median onset of nausea was within one-hour post-dose and lasted about two hours in duration.
The incidence of nausea was highest after the first VYLEESI dose (reported in 21% of patients) then declined to about 3% after subsequent doses.
Thirteen percent of VYLEESI-treated patients received an anti-emetic medication.
Overall, 8% of VYLEESI-treated patients and no placebo-treated patients prematurely discontinued the trials due to nausea.
[see Warnings and Precautions ( 5.3 )] In a phase 4, single-dose, placebo-controlled clinical study, pre-treatment with oral ondansetron (a 5-HT 3 receptor antagonist) did not reduce the incidence of nausea associated with VYLEESI treatment.
In this study, 228 healthy women were randomized (1:1) to receive 8 mg ondansetron or placebo orally 30 minutes prior to a single administration of 1.75 mg of VYLEESI given subcutaneously.
No significant difference in the incidence of VYLEESI-associated nausea was seen between the treatment groups.
Therefore, pre-treatment with oral ondansetron given 30 minutes prior to VYLEESI administration does not reduce the incidence of VYLEESI-associated nausea and is not recommended.
Treatment with ondansetron after VYLEESI administration or after the onset of nausea has not been formally studied.
Headache In the pooled phase 3 placebo-controlled trials, headache occurred at a higher incidence in VYLEESI-treated patients (11%) than placebo-treated patients (2%).
One patient experienced a headache event that was serious (intractable pain leading to hospitalization) and 1% of patients who received VYLEESI discontinued the study due to headache.
Flushing In the pooled phase 3 placebo-controlled trials, flushing occurred more frequently in VYLEESI-treated patients (20%) than placebo-treated patients (<1%).
None of the flushing events were serious and few were severe (<1%), and 1% of patients who received VYLEESI discontinued the study due to flushing.
Less Common Adverse Reactions Less common adverse reactions occurring in <2% of VYLEESI-treated patients and at an incidence greater than in the placebo group were upper abdominal pain, diarrhea, myalgia, arthralgia, pain, restless leg syndrome, rhinorrhea, increased creatine phosphokinase, blood pressure increased, pain in extremity and focal skin hyperpigmentation.
Acute hepatitis In the open-label, uncontrolled extension phase of one study, a single case of acute hepatitis was reported in a patient who had received 10 doses of VYLEESI over one year.
She presented with serum transaminases exceeding 40 times the upper limit of normal (ULN), total bilirubin 6 times the ULN, and alkaline phosphatase less than 2 times ULN.
Liver tests returned to normal 4 months after study drug discontinuation.
Because another etiology was not identified, the role of VYLEESI could not definitively be excluded.
There was no imbalance between treatment groups in serum transaminase outliers or other signals for hepatotoxicity in the clinical development program.