The Definitive Peptide Research Reference Guide — Compound Review

FDA Approved

PT-141 (Bremelanotide) Clinical Trials & FDA Approval

Complete clinical trial history of PT-141/bremelanotide: 23 clinical studies, Phase 3 RECONNECT trial data, FDA approval as Vyleesi (2019), mechanism of action, and what the evidence shows for HSDD.

FDA-approved as Vyleesi (2019)
23 clinical studies
MC4R agonist mechanism

Research Disclaimer

The information provided on this page is for educational and informational purposes only and does not constitute medical advice. PT-141 (Bremelanotide) is a research chemical and is not approved for human consumption outside of specific clinical applications (Vyleesi\u00ae). Always consult with a qualified healthcare professional before making any decisions about your health or treatment.

The Unique Status of PT-141: FDA Approval as Vyleesi\u00ae

Among the various peptides discussed on Compound Review, PT-141 (bremelanotide) holds a distinctive position: it is the **only peptide on this site that has received FDA approval for human therapeutic use**. Specifically, bremelanotide 1.75 mg was approved on June 21, 2019, under the brand name Vyleesi\u00ae, for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This critical distinction means that, unlike research chemicals such as BPC-157 or Sermorelin, PT-141 has undergone rigorous clinical development, including a comprehensive New Drug Application (NDA) dataset submitted to and reviewed by the U.S. Food and Drug Administration.

The FDA approval of Vyleesi\u00ae underscores a significant milestone in sexual medicine, providing a prescription treatment option for a condition that affects millions of women. This extensive regulatory pathway provides a wealth of clinical data, offering a robust foundation for understanding its efficacy, safety, and mechanism of action.

Understanding PT-141's Central Mechanism of Action

PT-141 functions as a **melanocortin receptor agonist**, primarily targeting the melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) in the central nervous system. This mechanism sets it apart from other common sexual dysfunction treatments, such as PDE5 inhibitors (e.g., Viagra, Cialis), which primarily act on vascular smooth muscle to increase blood flow to genital tissues.

Bremelanotide's action is fundamentally different: it works centrally within the brain, specifically in the hypothalamus, to activate neural pathways associated with sexual desire and arousal. By modulating these central pathways, PT-141 addresses the psychological and neurological components of sexual function, rather than just the physical aspects of arousal. This central mode of action explains why it has shown efficacy in both men and women and targets the underlying desire, making it a unique therapeutic agent in the landscape of sexual health.

The activation of MC4R, in particular, is believed to play a crucial role in regulating sexual behavior and appetite. This central modulation leads to an increase in sexual desire and responsiveness, offering a novel approach to treating conditions like HSDD.

Pivotal Phase 3 RECONNECT Trials: Efficacy in HSDD

The FDA approval of Vyleesi\u00ae was largely based on the results of two identical, randomized, double-blind, placebo-controlled, Phase 3 clinical trials: **RECONNECT-1 (NCT02338960)** and **RECONNECT-2 (NCT02338947)**. These trials enrolled premenopausal women with acquired, generalized HSDD.

The primary efficacy endpoints for both trials were the change from baseline in the number of satisfying sexual events (SSEs) per month and the change in the Female Sexual Function Index (FSFI) desire domain score. Participants self-administered bremelanotide as needed via subcutaneous injection.

**Key Findings from RECONNECT-1 and RECONNECT-2:**

  • Bremelanotide significantly increased the number of SSEs per month by approximately 0.7 events compared to placebo.
  • A statistically significant improvement was observed in the FSFI desire domain score, indicating enhanced sexual desire.
  • A greater proportion of bremelanotide-treated patients reported clinically meaningful improvements in both SSEs and distress associated with low sexual desire.

These positive outcomes, demonstrating both statistical significance and clinical relevance, formed the cornerstone of the New Drug Application (NDA 210557) that ultimately led to the FDA's approval of Vyleesi\u00ae in June 2019.

A Comprehensive Clinical Development Program: 23 Studies

The journey to FDA approval for bremelanotide involved a comprehensive clinical development program encompassing 23 clinical studies. This extensive research included various phases, each designed to evaluate different aspects of the peptide's pharmacology, safety, and efficacy.

  • **Phase 1 Studies:** Focused on pharmacokinetics (PK), pharmacodynamics (PD), and initial safety assessments in healthy volunteers. These studies established the absorption, distribution, metabolism, and excretion profile of bremelanotide.
  • **Phase 2 Dose-Finding Studies:** Trials such as NCT01382719 explored different dosages of bremelanotide to determine the optimal therapeutic dose with an acceptable safety profile for HSDD. These studies helped refine the treatment regimen that would later be tested in larger Phase 3 trials.
  • **Phase 3 RECONNECT Trials:** As detailed above, these pivotal trials confirmed the efficacy and safety of the selected dose in a larger patient population, providing the robust data required for regulatory submission.
  • **Long-term Safety Studies:** Additional studies were conducted to assess the long-term safety and tolerability of bremelanotide, monitoring for any emergent adverse events over extended periods of use.

This rigorous and multi-faceted clinical program highlights the thorough evaluation bremelanotide underwent, distinguishing it from many other research peptides.

Common Side Effects Observed in Clinical Trials

During the extensive clinical trials for bremelanotide, several side effects were commonly reported. It is important for both researchers and potential users to be aware of these, particularly given the peptide's central mechanism of action and its impact on physiological systems.

Adverse EventIncidence (Approx.)Notes
Nausea40%Most common, typically mild to moderate and transient.
Flushing20%Reddening of the skin, often in the face and neck.
Headache11%Reported by a notable percentage of participants.
Injection Site Reactions~10%Pain, redness, or bruising at the injection site.
Transient Blood Pressure IncreaseVariableContraindicated in patients with uncontrolled hypertension or cardiovascular disease.
Dizziness~5%Mild to moderate.

Source: FDA prescribing information for Vyleesi\u00ae (bremelanotide injection).

Key Clinical Trials and Research Highlights

RECONNECT-1 (NCT02338960)

Clayton et al., 2017. Journal of Women's Health.

**Finding:** Bremelanotide significantly increased satisfying sexual events (SSEs) and improved distress associated with HSDD in premenopausal women.

**Mechanism/Relevance:** Pivotal Phase 3 trial supporting FDA approval for HSDD, demonstrating efficacy through central melanocortin receptor activation.

RECONNECT-2 (NCT02338947)

Kingsberg et al., 2017. Obstetrics & Gynecology.

**Finding:** Consistent with RECONNECT-1, bremelanotide showed significant improvements in SSEs and FSFI desire domain scores compared to placebo.

**Mechanism/Relevance:** Replicated efficacy findings, reinforcing the drug's potential as a treatment for HSDD and contributing to the comprehensive NDA submission.

Phase 2 Dose-Finding Study (NCT01382719)

Palatin Technologies, 2012. ClinicalTrials.gov.

**Finding:** Identified optimal dose ranges for bremelanotide, demonstrating dose-dependent increases in sexual desire and arousal in women with HSDD.

**Mechanism/Relevance:** Crucial for establishing the therapeutic window and informing the design of subsequent Phase 3 trials.

Pharmacokinetics and Safety in Healthy Subjects

Diamond et al., 2004. Journal of Clinical Pharmacology.

**Finding:** Characterized the pharmacokinetic profile of bremelanotide and established its initial safety and tolerability in healthy male and female volunteers.

**Mechanism/Relevance:** Early-phase research essential for understanding drug absorption, distribution, metabolism, and excretion, foundational for later clinical development.

Bremelanotide for Male Erectile Dysfunction

Rosen et al., 2004. International Journal of Impotence Research.

**Finding:** Early studies explored bremelanotide's potential in men with erectile dysfunction, showing some positive effects on erectile function and sexual desire.

**Mechanism/Relevance:** While not the primary focus of FDA approval, this research highlighted the broad applicability of melanocortin agonism to sexual function in both sexes.

Off-label Research: Post-SSRI Sexual Dysfunction

Various anecdotal reports and small studies.

**Finding:** Limited exploratory research suggests potential for PT-141 in addressing sexual dysfunction induced by selective serotonin reuptake inhibitors (SSRIs).

**Mechanism/Relevance:** Highlights an area of ongoing interest for melanocortin system modulation, though robust clinical evidence is still lacking for this indication.

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Frequently Asked Questions About PT-141

What is PT-141 (Bremelanotide)?

PT-141, also known as bremelanotide, is a synthetic peptide analog of alpha-melanocyte-stimulating hormone (α-MSH). It acts as a melanocortin receptor agonist, primarily targeting MC3R and MC4R, and is known for its role in sexual function. It is the active pharmaceutical ingredient in Vyleesi®.

What is Vyleesi®?

Vyleesi® is the brand name for bremelanotide 1.75 mg, an injectable medication approved by the FDA in 2019 for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. It is administered via subcutaneous injection at least 45 minutes before anticipated sexual activity.

How does PT-141 work?

Unlike traditional erectile dysfunction medications that affect vascular smooth muscle, PT-141 works centrally in the brain, specifically in the hypothalamus. It activates melanocortin receptors (MC3R and MC4R) to influence neural pathways involved in sexual arousal and desire, addressing the psychological component of sexual dysfunction.

What is Hypoactive Sexual Desire Disorder (HSDD)?

HSDD is characterized by a persistent or recurrent deficiency or absence of sexual fantasies and desire for sexual activity, causing marked distress or interpersonal difficulty. It is not attributable to another medical condition, substance, or other mental disorder.

What were the key findings of the Phase 3 RECONNECT trials?

The RECONNECT-1 and RECONNECT-2 trials were pivotal Phase 3 studies that evaluated the efficacy and safety of bremelanotide for HSDD. They demonstrated a statistically significant increase in satisfying sexual events (SSEs) and improvements in the Female Sexual Function Index (FSFI) desire domain compared to placebo, leading to FDA approval.

What are the common side effects of PT-141/Vyleesi®?

The most common side effects observed in clinical trials included nausea (approximately 40%), flushing (20%), headache (11%), and injection site reactions. Transient increases in blood pressure and decreases in heart rate were also noted. It is contraindicated in patients with uncontrolled hypertension or known cardiovascular disease.

Can men use PT-141?

While Vyleesi® is FDA-approved specifically for HSDD in premenopausal women, some off-label research has explored PT-141 for male sexual dysfunction, including erectile dysfunction and post-SSRI sexual dysfunction. However, data for these indications are limited and it is not an FDA-approved treatment for men.

Where can I buy research-grade PT-141?

Research-grade PT-141 is available from specialized suppliers for laboratory and research purposes only. It is not approved for human consumption outside of clinical trials. Always ensure you are purchasing from reputable sources that provide third-party testing and quality assurance for research chemicals.

Medical Disclaimer: All content on this site is for educational and research purposes only. Research peptides are not FDA-approved for human use. Always consult a qualified healthcare professional before considering any peptide or supplement protocol. Nothing on this site constitutes medical advice, diagnosis, or treatment.