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Companies Take Aim at MRSA Infections

Chris Fellner

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most widespread and virulent nosocomial pathogens.1 MRSA is categorized as either health care-associated MRSA (HA-MRSA)2 or community-associated MRSA (CA-MRSA),3 depending on the setting where the infection was acquired. In medical facilities, MRSA may cause life-threatening bloodstream infections, pneumonia, or surgical-site infections. In the community, most MRSA infections affect the skin.4

Although MRSA remains a major patient threat, data from the Centers for Disease Control and Prevention (CDC) have shown that the rate of invasive (life-threatening) MRSA infections in health care settings is declining. Invasive MRSA infections that began in hospitals dropped 54% between 2005 and 2011, with 30,800 fewer severe infections. The study showed 9,000 fewer deaths in hospital patients in 2011 than in 2005.1

Most patients who present to U.S. hospitals with suspected MRSA infections receive empiric antimicrobial therapy before the causative pathogen has been diagnosed and confirmed. Culture-based methods are still the gold standard for detecting MRSA.5

At least 10 marketed antibiotics have demonstrated potent activity against MRSA and are used to treat invasive HA-MRSA infections in the U.S. (Table 1). Vancomycin, a generic glycopeptide, is the most frequently prescribed antibiotic for infections in which MRSA is the suspected or known cause, followed by linezolid (Zyvox, Pfizer), an oxazolidinone, and daptamycin (Cubicin, Merck), a lipopeptide.5

The late-stage clinical pipeline for MRSA includes an array of treatments aimed at acute bacterial skin and skin-structure infections (ABSSSIs) and/or community-acquired bacterial pneumonia (Table 2). Three of these products—brilacidin (Cellceutix Corp.), Debio1450 (Debiopharm International), and lefamulin (Nabriva Therapeutics)—are expected to be first-in-class agents. The others include a new macrolide derivative (solithromycin, Cempra Pharmaceuticals); a next-generation tetracycline derivative (omadacycline, Paratek Pharmaceuticals); a proprietary oral formulation of fusidic acid (Taksta, Cempra Pharmaceuticals); and two anti-MRSA fluoroquinolones (delafloxacin, Melinta Therapeutics; and KRP-AM1977X, Kyorin Pharmaceutical).57

While these new treatments are expected to succeed, analysts foresee stiff competition from generic products, spurred by the loss of patent protection for two leading MRSA therapies, linezolid and daptamycin.5

Tables

Antibacterial Agents Most Commonly Used to Treat U.S. Hospital-Acquired MRSA Infectionsa

Product Company Indication(s) Dosageb Cost of Treatmentc
Cephalosporin
Ceftaroline fosamil (Teflaro) Actavis, Inc. ABSSSIs, CABP 600 mg every 12 hours by IV infusion administered over 5–60 minutes for 5–14 days (ABSSSIs) or 5–7 days (CABP) in adults (18 years of age or older) 5–14 days: $1,831–$5,127
Glycycycline
Tigecycline (Tygacil) Pfizer ABSSSIs, CABP, CIAIs Initial dose: 100 mg, followed by 50 mg every 12 hours IV over approximately 30–60 minutes for 5–14 days (ABSSSIs and CIAIs) or 7–14 days (CABP) 5–14 days: $1,888–$4,977
Glycopeptides and Lipoglycopeptides
Dalbavancin (Dalvance) Allergan ABSSSIs Two-dose regimen: 1,000 mg IV followed 1 week later by 500 mg IV, both administered over 30 minutes $5,364
Oritavancin (Orbactiv) The Medicines Company ABSSSIs 1,200-mg single dose by IV infusion over 3 hours in adults $3,480
Telavancin (Vibativ) Theravance Biopharma US ABSSSIs, HABP, VABP
  • ABSSSIs: 10 mg/kg by IV infusion over 60 minutes every 24 hours for 7–14 days
  • HABP/VABP: 10 mg/kg by IV infusion over 60 minutes every 24 hours for 7–21 days
7–21 days: M, $3,523–$10,568; F: $3,002–$9,007e
Vancomycin Generics Serious or severe infections caused by susceptible methicillin-resistant (beta-lactam-resistant) staphylococci
  • Adults: 2 g IV daily, divided as 500 mg every 6 hours or 1 g every 12 hours, administered at no more than 10 mg/min or over a period of at least 60 minutes, whichever is longer, for 7–10 daysd
  • Pediatric patients: 10 mg/kg IV every 6 hours over a period of at least 60 minutes for 7–10 daysd
7–10 days (adults): $101–$144
Lipopeptide
Daptomycin (Cubicin) Merck ABSSSIs, S. aureus bacteremia

    Adults with ABSSSIs (for 7–14 days):

  • ° CLCR ≥ 30 mL/min: 4 mg/kg once every 24 hours
  • ° CLCR < 30 mL/min: 4 mg/kg once every 48 hours

Adults with bacteremia (for 14–42 days):

  • ° CLCR ≥ 30 mL/min: 6 mg/kg once every 24 hours
  • ° CLCR < 30 mL/min: 6 mg/kg once every 48 hours
    • 4 mg/kg, 7–14 days: M, $2,634–$5,269; F, $2,245–$4,491
    • 6 mg/kg, 14–42 days: M, $7,903–$23,710, F, $6,736–$20,208e
    Oxazolidinones
    Linezolid (Zyvox) Pfizer ABSSSIs, CABP, HABP, uncomplicated SSSIs, vancomycin-resistant Enterococcus faecium infections
    • ABSSSIs, CAP, HABP in adults/adolescents: 600 mg IV or oral every 12 hours for 10–14 days
    • Uncomplicated SSSIs in adults: 400 mg oral every 12 hours for 10–14 days
    • Uncomplicated SSSIs in adolescents: 600 mg oral every 12 hours for 10–14 days
    • Vancomycin-resistant E. faecium infections in adults/adolescents: 600 mg IV or oral every 12 hours for 14–28 days
    • 600 mg, 10–28 days: IV, $1,920–$5,376; oral, $4,082–$11,429
    • 400 mg, oral, 10–14 days: $2,978–$4,169
    Tedizolid phosphate (Sivextro) Merck ABSSSIs 200 mg once daily IV or oral over 1 hour for 6 days
    • IV: $1,777
    • Oral: $2,230

    aAgents are listed alphabetically, not by preferred use. This list is not all-inclusive. Additional therapies may be available.

    bBased on prescribing information; doses and schedules may vary due to patient-specific requirements.

    cCosts calculated using average wholesale price for regimens in prescribing information for adults with normal kidney function, rounded to the nearest dollar.

    dRepresentative dosing for sterile vancomycin hydrochloride USP (Pfizer).

    ePrice calculated using weights of 88 kg for men and 75 kg for women.

    ABSSSIs = acute bacterial skin and skin-structure infections; CABP = community-acquired bacterial pneumonia; CIAIs = complicated intra-abdominal infections;

    CLCR = creatinine clearance; F = female; HABP = hospital-acquired bacterial pneumonia; IV = intravenous; M = male; SSSIs = skin and skin-structure infections; VABP = ventilator-associated bacterial pneumonia.

    Sources: GlobalData, product prescribing information, Red Book Online

    Promising Drugs in Late-Stage Clinical Development for the Treatment of MRSA Infections

    Product Company Therapeutic Class Lead Indication Status Expected U.S. Pricing Strategy Expected U.S. Launch Date
    Brilacidin Cellceutix Corp. Defensin-mimetic ABSSSIs Phase 3 Priced at 5% premium over average daily cost of linezolid due to its first-in-class status and ability to be administered as single IV infusion; estimated cost of 7-day regimen, $2,711 2019
    Debio 1450 (Debio 1452 prodrug) Debiopharm International Fabl enzyme inhibitor ABSSSIs Phase 2 Priced at 25% premium over average daily cost of linezolid because of its first-in-class status and narrow spectrum of activity; estimated cost of 10-day regimen, $4,611 2020
    Delafloxacin (RX-3341) Melinta Therapeutics Fluoroquinolone ABSSSIs Phase 3 Priced at 10% premium over average daily cost of ceftaroline fosamil due to its status as novel fluoroquinolone specifically indicated for MRSA and because of its oral and IV formulations; estimated cost of 10-day regimen, $3,055 2017
    KRP-AM1977X Kyorin Pharmaceutical Fluoroquinolone CABP Phase 3 (Japan) Priced equal to average daily cost of delafloxacin (Baxdela, Melinta Therapeutics, now in phase 3 development for ABSSSIs); estimated U.S. cost undetermined 2018
    Lefamulin (BC-3781) Nabriva Therapeutics Systemic pleuromutilin CABP Phase 2/3 Priced at 20% premium over average daily cost of ceftaroline fosamil because of its first-in-class status; estimated cost of 12-day regimen, $3,999 2019
    Omadacycline (PTK-0796) Paratek Pharmaceuticals Aminomethylcycline (tetracycline derivative) ABSSSIs, CABP Phase 3 Priced at 15% premium over average daily cost of tigecycline (Tygacil, Pfizer) because of more-convenient once-daily dosing, oral and IV formulations, and improved safety profile; estimated cost of 10-day regimen, $2,741 2019
    Solithromycin Cempra Pharmaceuticals Fluoroketolide (macrolide derivative) CABP Phase 3 Priced at 5% premium over average daily cost of ceftaroline fosamil because of its next-generation macrolide status and oral and IV formulations; estimated cost of 5-day regimen, $1,458 2017
    Taksta Cempra Pharmaceuticals Fusidic acid (proprietary oral formulation) ABSSSIs Phase 2/3 Priced at 5% premium over average daily cost of linezolid because of its first-in-class status; estimated cost of 10-day regimen, $4,058 2018

    ABSSSIs = acute bacterial skin and skin-structure infections; CABP = community-acquired bacterial pneumonia.

    Sources: GlobalData (December 2015),5 company websites

    Author bio: 
    Chris Fellner is a medical writer and the Editor of PTCommunity.com.

    References

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