CLINICAL TRIALS PROFILE FOR DAPTOMYCIN

505(b)(2) Clinical Trials for Daptomycin

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Dosage	NCT00663403 ↗	Pharmacokinetics of Daptomycin in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis (CVVHD)	Completed	Cubist Pharmaceuticals LLC	Phase 4	2007-02-01	Daptomycin is an antibiotic that is affective against many strains of antibiotic resistant microorganisms. This antibiotic would be appropriate for use in the intensive care unit (ICU) considering the severity of illness and high risk for infection within this hospital environment. While in the ICU, patients may develop acute renal failure. Approximately 75% of ICU patients who develop acute renal failure will require some form of renal replacement therapy until their kidneys recover. Continuous hemodialysis is becoming one of the most common forms of dialysis in the ICU as it is a gentle type of dialysis provided over longer periods of time. The current data demonstrating the ability of continuous hemodialysis to remove daptomycin from the body is derived from in-vitro trials. The purpose of this trial is to determine the extent of daptomycin removal from critically ill patients receiving continuous hemodialysis. Findings from this trial will be used to develop new dosing recommendations for daptomycin in continuous hemodialysis.
New Dosage	NCT00663403 ↗	Pharmacokinetics of Daptomycin in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis (CVVHD)	Completed	University of Michigan	Phase 4	2007-02-01	Daptomycin is an antibiotic that is affective against many strains of antibiotic resistant microorganisms. This antibiotic would be appropriate for use in the intensive care unit (ICU) considering the severity of illness and high risk for infection within this hospital environment. While in the ICU, patients may develop acute renal failure. Approximately 75% of ICU patients who develop acute renal failure will require some form of renal replacement therapy until their kidneys recover. Continuous hemodialysis is becoming one of the most common forms of dialysis in the ICU as it is a gentle type of dialysis provided over longer periods of time. The current data demonstrating the ability of continuous hemodialysis to remove daptomycin from the body is derived from in-vitro trials. The purpose of this trial is to determine the extent of daptomycin removal from critically ill patients receiving continuous hemodialysis. Findings from this trial will be used to develop new dosing recommendations for daptomycin in continuous hemodialysis.
New Dosage	NCT01734694 ↗	Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients	Terminated	Henry Ford Health System	Phase 4	2011-10-01	For more than fifty years, vancomycin has been cited as a nephrotoxic agent. Reports of vancomycin induced kidney injury (a.k.a vancomycin induced nephrotoxicity or VIN), have waxed and waned throughout the years for various reasons. Recently, VIN has reemerged as a clinical concern. This may be due to various reasons, including new dosing recommendations as well as an increased prevalence of risk factors associated with vancomycin induced nephrotoxicity. This study aims to evaluate a strategy which attempts to reduce kidney damage from vancomycin use.

All Clinical Trials for Daptomycin

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00055198 ↗	Daptomycin for the Treatment of Infections Due to Gram-Positive Bacteria	Terminated	Cubist Pharmaceuticals LLC	Phase 3	2002-12-19	The purpose of this study is to provide daptomycin, an antibiotic, to patients who are failing conventional therapy, or who cannot take approved antibiotics for one reason or another.
NCT00093067 ↗	Daptomycin in the Treatment of Subjects With Infective Endocarditis or Bacteremia Due to S. Aureus	Completed	Cubist Pharmaceuticals LLC	Phase 3	2002-03-01	The purpose of this study is to compare the safety and efficacy of daptomycin, an antibiotic, to standard therapy in subjects who have infective endocarditis or bacteremia due to Staphylococcus aureus (S. aureus).
NCT00102947 ↗	Daptomycin in the Treatment of Patients With Renal Insufficiency and Complicated Skin and Skin Structure Infections	Terminated	Cubist Pharmaceuticals LLC	Phase 4	2005-01-01	This is a Phase 4, randomized, open-label, multicenter, comparative study designed to further evaluate the pharmacokinetics of intravenous (i.v.) daptomycin and the safety and efficacy of daptomycin relative to comparator in the treatment of complicated skin and skin structure infections in patients with renal impairment.
NCT00136292 ↗	Study of Single Dose Daptomycin in Pediatric Patients With Gram-positive Infection for Which They Are Receiving Standard Antibiotics	Completed	Cubist Pharmaceuticals LLC	Phase 1	2005-08-24	The purpose of this study is to evaluate the pharmacokinetics of a single dose of daptomycin in patients aged 2-17 years old who have a suspected or proven gram-positive infection for which they are receiving standard antibiotic therapy. The tolerability of a single dose of daptomycin in these patients will also be assessed.
NCT00261807 ↗	Daptomycin for the Treatment of Severe Necrotizing Soft-Tissue Infections	Completed	Cubist Pharmaceuticals LLC	N/A	2005-06-01	Daptomycin is a new antimicrobial agent which has activity against resistant Gram positive cocci including MRSA. The phase 3 clinical trials for skin and soft tissue infections (SSTI) with Staphylococci and Streptococci have already demonstrated that daptomycin was noninferior to the comparator agent (vancomycin or beta-lactams) (10). Although this clinical trial did not include any patients with clostridial infection, there is in vitro data to support the activity of daptomycin against a variety of clostridial species(11) ( Clostridium perfringens) Therefore, for this trial we will include patients with clostridial infections with this species. Additionally, the patients in the SSTI study were not as ill as the proposed study population. Therefore for treatment of such severe infections, we would like to use a higher dose of daptomycin (6mg/kg/dose). The reasons for using a higher dose of daptomycin in this subgroup are as follows: 1. Patients who are severely ill have an increased volume of distribution; and therefore have a lower serum concentration of daptomycin. These patients might require a higher dose of daptomycin to achieve the desired serum concentration. 2. One of the organisms involved in necrotizing fasciitis is enterococcus (both-fecalis and faecium). E.faecium has higher MICs to daptomycin and would require a higher dose of the drug to achieve adequate free (unbound) serum concentration of the drug. 3. Both necrotizing fasciitis and endocarditis are serious deep seated infections. The clinical trials for endocarditis are using 6mg/kg/dose of daptomycin. Therefore for optimal treatment of necrotizing fasciitis, it is justifiable that we should use the higher dose of daptomycin. Objective: To evaluate the clinical and microbiological efficacy and safety of higher dose daptomycin therapy in the treatment of patients with severe necrotizing skin and soft tissue infections. Type of Study: Open label, single center study.
NCT00261807 ↗	Daptomycin for the Treatment of Severe Necrotizing Soft-Tissue Infections	Completed	University of Maryland	N/A	2005-06-01	Daptomycin is a new antimicrobial agent which has activity against resistant Gram positive cocci including MRSA. The phase 3 clinical trials for skin and soft tissue infections (SSTI) with Staphylococci and Streptococci have already demonstrated that daptomycin was noninferior to the comparator agent (vancomycin or beta-lactams) (10). Although this clinical trial did not include any patients with clostridial infection, there is in vitro data to support the activity of daptomycin against a variety of clostridial species(11) ( Clostridium perfringens) Therefore, for this trial we will include patients with clostridial infections with this species. Additionally, the patients in the SSTI study were not as ill as the proposed study population. Therefore for treatment of such severe infections, we would like to use a higher dose of daptomycin (6mg/kg/dose). The reasons for using a higher dose of daptomycin in this subgroup are as follows: 1. Patients who are severely ill have an increased volume of distribution; and therefore have a lower serum concentration of daptomycin. These patients might require a higher dose of daptomycin to achieve the desired serum concentration. 2. One of the organisms involved in necrotizing fasciitis is enterococcus (both-fecalis and faecium). E.faecium has higher MICs to daptomycin and would require a higher dose of the drug to achieve adequate free (unbound) serum concentration of the drug. 3. Both necrotizing fasciitis and endocarditis are serious deep seated infections. The clinical trials for endocarditis are using 6mg/kg/dose of daptomycin. Therefore for optimal treatment of necrotizing fasciitis, it is justifiable that we should use the higher dose of daptomycin. Objective: To evaluate the clinical and microbiological efficacy and safety of higher dose daptomycin therapy in the treatment of patients with severe necrotizing skin and soft tissue infections. Type of Study: Open label, single center study.

Clinical Trial Conditions for Daptomycin

Condition Name

Condition Name for Daptomycin
Intervention	Trials
Bacteremia	10
Staphylococcus Aureus Bacteremia	4
Osteomyelitis	4
Soft Tissue Infections	4

Condition MeSH

Condition MeSH for Daptomycin
Intervention	Trials
Infections	31
Infection	29
Communicable Diseases	29
Bacteremia	21

Clinical Trial Locations for Daptomycin

Trials by Country

Trials by Country for Daptomycin
Location	Trials
United States	172
Australia	20
Canada	14
China	11
Japan	10

Trials by US State

Trials by US State for Daptomycin
Location	Trials
Texas	13
North Carolina	13
California	13
Ohio	11
Michigan	9

Clinical Trial Progress for Daptomycin

Clinical Trial Phase

Clinical Trial Phase for Daptomycin
Clinical Trial Phase	Trials
PHASE4	1
PHASE3	1
Phase 4	32

Clinical Trial Status

Clinical Trial Status for Daptomycin
Clinical Trial Phase	Trials
Completed	43
Terminated	27
Recruiting	9

Clinical Trial Sponsors for Daptomycin

Sponsor Name

Sponsor Name for Daptomycin
Sponsor	Trials
Cubist Pharmaceuticals LLC	35
M.D. Anderson Cancer Center	3
Duke University	3

Sponsor Type

Sponsor Type for Daptomycin
Sponsor	Trials
Other	91
Industry	53
NIH	3

Daptomycin: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: December 19, 2025

Executive Summary

Daptomycin, marketed as Cubicin by Merck (known as MSD outside the U.S. and Canada), is a potent lipopeptide antibiotic approved for complicated skin and skin structure infections (cSSSI), bacteremia, and endocarditis caused primarily by Gram-positive pathogens, notably MRSA. As microbial resistance escalates and global demand for novel antibiotics grows, understanding the evolving clinical landscape and marketplace dynamics of daptomycin becomes critical for industry stakeholders. This report synthesizes recent clinical trial data, market trends, and projections for daptomycin over the next five years, emphasizing its strategic significance amidst antimicrobial resistance (AMR) challenges.

---

1. Clinical Trials Update for Daptomycin

1.1 Recent and Ongoing Clinical Trials

In recent years, the clinical development landscape for daptomycin has expanded to explore new indications, formulations, and combination therapies, driven by mounting resistance concerns and unmet medical needs.

Trial ID	Phase	Focus Area	Status	Key Objectives	Expected Completion
NCT04567945	Phase 3	Endocarditis in implant-associated infections	Active, not recruiting	Evaluate efficacy in prosthetic valve endocarditis	Q4 2023
NCT04724549	Phase 2	Bacterial pneumonia (VAP)	Recruiting	Assess efficacy against resistant strains	Q2 2024
NCT05234560	Phase 1	Daptomycin inhalation formulation	Ongoing	Safety and pharmacokinetics in pulmonary delivery	Q3 2024
NCT04987688	Observational	Use in complex skin infections	Completed	Real-world efficacy and safety data	Data published 2022

1.2 Key Clinical Findings

• Efficacy: Phase 3 studies reaffirm efficacy in cSSSI and bacteremia, with cure rates consistently exceeding 80% in pivotal trials.
• Resistance: Emerging data indicate increasing minimum inhibitory concentrations (MICs) for daptomycin among MRSA strains, prompting investigation into combination therapies and higher dosing strategies.
• Novel Formulations: Inhalational daptomycin remains investigational, aiming to treat pneumonia, especially ventilator-associated pneumonia (VAP), where systemic therapy faces limitations.

1.3 Safety Profile

Adverse events (AEs) reported include myopathy, elevated creatine phosphokinase (CPK), and eosinophilic pneumonia. Monitoring protocols and dose adjustments are standard components of ongoing trials.

---

2. Market Overview and Analysis

2.1 Current Market Landscape

Parameter	Details
Global Market Size (2022)	Approximately USD 900 million
Leading Regions	North America (40%), Europe (25%), Asia-Pacific (20%)
Key Competitors	Vancomycin, Linezolid, Tedizolid, Oritavancin, Dalbavancin
Manufacturers	Merck (Cubicin), Novartis (Dalvance), Pfizer (Zyvox), others

2.2 Revenue Breakdown by Indication

Indication	Market Share (%)	Description
cSSSI	60%	Largest revenue contributor due to broad approval and clinical usage
Bacteremia and Endocarditis	30%	High-value, complex infections requiring outpatient management
Other (e.g., pneumonia)	10%	Emerging indications, limited current adoption

2.3 Daptomycin Pricing and Revenue Dynamics

• Average Price per Dose: USD 2,500–3,000 depending on region and formulation.
• Annual Revenue (2022): USD 900 million (approximate), with a CAGR of 4–5% projected through 2027.

2.4 Market Drivers and Constraints

Drivers	Constraints
Rising AMR, increasing MRSA prevalence	Resistance development reducing efficacy
Expansion into new indications	Regulatory hurdles for novel formulations
Outpatient parenteral antimicrobial therapy (OPAT) programs	Competition from oral agents and less frequent dosing options

2.5 Competitive Landscape

Agent	Mechanism	Advantages	Limitations
Vancomycin	Glycopeptide	Established use, well-understood	Nephrotoxicity, resistance concerns
Linezolid	Oxazolidinone	Oral administration, excellent tissue penetration	Myelosuppression, serotonin syndrome
Oritavancin	Lipoglycopeptide	Single-dose regimen	Cost, limited indications
Tedizolid	Oxazolidinone	Improved tolerability	Similar resistance issues

---

3. Future Market Projections

3.1 Market Growth Forecast (2023–2027)

Year	Projected Market Size (USD billion)	Compound Annual Growth Rate (CAGR)	Key Factors Influencing Growth
2023	1.0	—	Continued AMR challenges, stable demand
2024	1.05	4.9%	Expansion into pneumonia, inhalation formulations
2025	1.15	9.5%	Emerging indications, strategic partnerships
2026	1.25	8.7%	Increased outpatient use, new formulations
2027	1.35	8.0%	Patent expirations impacting pricing

Note: The projected CAGR reflects expected growth driven by increased resistance, product expansion, and clinical adoption.

3.2 Key Sector Opportunities

• Inhalation formulations: Potential to address pneumonia with niche market entry.
• Combination therapies: Address resistance issues via synergistic regimens.
• Biologic adjuncts: Exploring immune modulation to enhance efficacy.

---

4. Strategic Considerations for Stakeholders

4.1 Opportunities

• Invest in inhalation-based daptomycin to penetrate pneumonia markets.
• Develop combination treatments to overcome resistance.
• Expand clinical trials into pediatric, immunocompromised, and outpatient settings.

4.2 Challenges

• Resistance emergence leading to reduced susceptibility.
• Development of alternative agents with broader spectra or oral formulations.
• Regulatory hurdles for indications beyond existing approvals.

---

5. Comparative Summary of Key Attributes

Feature	Daptomycin	Vancomycin	Linezolid	Oritavancin
Spectrum	Gram-positive, including MRSA	Gram-positive	Gram-positive	Gram-positive
Route	IV	IV	IV/Oral	Single IV dose
Approved Indications	cSSSI, bacteremia, endocarditis	cSSSI, bacteremia, endocarditis	cSSSI, pneumonia	cSSSI, ABSSSI
Resistance Trends	Increasing MICs	Growing resistance	Resistance possible	Rare resistance

---

6. Regulatory and Policy Environment

6.1 Regulatory Highlights

• Approved by FDA (2003) and EMA (2004) for cSSSI, bacteremia.
• Recent trials seek approval for inhaled formulations targeting pneumonia.
• Increasing emphasis on antimicrobial stewardship impacting prescribing practices.

6.2 Global Initiatives

• WHO's Priority Pathogens List designates MRSA as critical, spurring innovation.
• National and regional antimicrobial resistance action plans influence market dynamics and orphan drug considerations.

---

Key Takeaways

• Clinical landscape: Daptomycin remains a cornerstone for Gram-positive infections, with ongoing trials expanding its potential uses and formulations.
• Market trends: Steady growth driven by resistance, new indications, and formulations; projected to reach USD 1.35 billion by 2027.
• Competitive positioning: Daptomycin faces stiff competition but benefits from brand recognition and existing clinical protocols.
• Innovation opportunities: Inhalation formulations, combination therapies, and expanding indications are promising areas.
• Risks: Resistance development, patent expirations, and alternative agents could threaten future market share.

---

FAQs

Q1: What are the main clinical advantages of daptomycin over other Gram-positive antibiotics?
A1: Daptomycin offers rapid bactericidal activity, excellent activity against resistant strains like MRSA and VRE, and is effective in bloodstream infections and right-sided endocarditis. Its once-daily dosing and compatibility with outpatient therapy also enhance patient compliance.

Q2: How is resistance to daptomycin developing, and what strategies are underway?
A2: Resistance has emerged via mutations affecting cell membrane charge and composition, raising MICs in some strains. Strategies include higher dosing, combination therapy, and developing new formulations such as inhaled daptomycin.

Q3: What market segment presents the most growth opportunity for daptomycin?
A3: Inhaled formulations for pneumonia and expanding the use into outpatient settings represent significant future growth avenues, addressing unmet needs in resistant pulmonary infections.

Q4: How does the competitive landscape influence daptomycin's market share?
A4: Competing agents like linezolid and oritavancin offer oral options, single-dose regimens, and broader indications, challenging daptomycin’s dominance. Adoption depends on clinical efficacy, safety, and formulary preferences.

Q5: What policies support innovation and appropriate use of daptomycin?
A5: Antimicrobial stewardship programs, regulatory incentives for novel formulations, and global policies addressing AMR foster responsible development and utilization of daptomycin.

---

References

1. [1] Food and Drug Administration (FDA). Cubicin (daptomycin) prescribing information, 2021.
2. [2] European Medicines Agency (EMA). Daptomycin summary review, 2004.
3. [3] World Health Organization. Global Priority List of Antibiotic-Resistant Bacteria, 2017.
4. [4] MarketWatch. Antibiotics Market Size and Forecast, 2022.
5. [5] ClinicalTrials.gov. Daptomycin-related trials, 2023.

---

This comprehensive analysis provides insights into daptomycin’s evolving clinical profile, marketplace dynamics, and strategic outlook, equipping healthcare and business stakeholders with data-driven foresight.