Merck’s ZERBAXA® (ceftolozane and tazobactam) Met Primary Endpoints of
Non-Inferiority Compared to Meropenem in Pivotal Phase 3 Study of Adult Patients with Hospital-Acquired Bacterial Pneumonia or
Ventilator-Associated Bacterial Pneumonia
Company Plans to Submit Supplemental New Drug Applications in the US and EU
Merck & Co., Inc. (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the pivotal Phase 3
clinical study evaluating the company’s antibiotic ZERBAXA® (ceftolozane and tazobactam) at an investigational dose for
the treatment of adult patients with either ventilated hospital-acquired bacterial pneumonia (HABP) or ventilator-associated
bacterial pneumonia (VABP) met the pre-specified primary endpoints, demonstrating non-inferiority to meropenem, the active
comparator, in Day 28 all-cause mortality and in clinical cure rate at the test-of-cure visit. In the U.S., ZERBAXA is currently
indicated in adult patients for the treatment of complicated urinary tract infections, including pyelonephritis, caused by certain
Gram-negative microorganisms, and is indicated, in combination with metronidazole, in adult patients for the treatment of
complicated intra-abdominal infections caused by certain Gram-negative and Gram-positive microorganisms.
Based on these results, Merck plans to submit supplemental new drug applications to the U.S. Food and Drug Administration (FDA)
and European Medicines Agency (EMA) seeking regulatory approval of ZERBAXA for this potential new indication. The company plans to
submit results from the study for presentation at a future scientific conference.
“HABP and VABP are serious and life-threatening hospital related pulmonary infections, especially in patients with severe
underlying medical conditions,” said Dr. Roy Baynes, senior vice president, head of global clinical development and chief medical
officer, Merck Research Laboratories. “The results from the ASPECT-NP study demonstrate the potential role of ZERBAXA for the
treatment of patients with HABP and VABP.”
About the ASPECT-NP study
This prospective, randomized, double-blind, multicenter, non-inferiority, Phase 3 study assessed the safety and efficacy of
ZERBAXA compared with meropenem in 726 adult patients diagnosed with either ventilated HABP or VABP requiring intravenous
antibiotic therapy. In the study, ZERBAXA was administered in an investigational 3g dose compared with meropenem 1g, each given
intravenously every eight hours for 8 to 14 days, or for 14 days for Pseudomonas aeruginosa infection. Meropenem is an
approved broad-spectrum injectable antibiotic widely used to treat serious infections.
Additional details about the study can be found online at
https://www.clinicaltrials.gov/ct2/show/NCT02070757.
About ZERBAXA (ceftolozane and tazobactam)
ZERBAXA is an antibacterial combination product for intravenous infusion consisting of the cephalosporin antibacterial drug
ceftolozane sulfate and the beta-lactamase inhibitor tazobactam sodium.
ZERBAXA 1.5g (ceftolozane 1g and tazobactam 0.5g) is approved in the United States and is indicated in adult patients for the
treatment of complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following Gram-negative
microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa.
ZERBAXA used in combination with metronidazole is indicated in adult patients for the treatment of complicated intra-abdominal
infections (cIAI) caused by the following Gram-negative and Gram-positive microorganisms: Enterobacter cloacae,
Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas
aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and
Streptococcus salivarius.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZERBAXA and other antibacterial drugs,
ZERBAXA should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When
culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In
the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Important Safety Information about ZERBAXA
Patients with renal impairment: Decreased efficacy of ZERBAXA has been observed in patients with baseline creatinine
clearance (CrCl) of 30 to ≤50 mL/min. In a clinical trial, patients with cIAIs with CrCl >50 mL/min had a clinical cure rate of
85.2% when treated with ZERBAXA (ceftolozane and tazobactam) plus metronidazole vs. 87.9% when treated with meropenem. In the same
trial, patients with CrCl 30 to ≤50 mL/min had a clinical cure rate of 47.8% when treated with ZERBAXA plus metronidazole vs. 69.2%
when treated with meropenem. A similar trend was also seen in the cUTI trial. Monitor CrCl at least daily in patients with changing
renal function and adjust the dose of ZERBAXA accordingly.
Hypersensitivity: ZERBAXA is contraindicated in patients with known serious hypersensitivity to ceftolozane/tazobactam,
piperacillin/tazobactam, or other members of the beta-lactam class. Serious and occasionally fatal hypersensitivity (anaphylactic)
reactions have been reported in patients receiving beta-lactam antibacterials. Before initiating therapy with ZERBAXA, make careful
inquiry about previous hypersensitivity reactions to cephalosporins, penicillins, or other beta-lactams. If an anaphylactic
reaction to ZERBAXA occurs, discontinue use and institute appropriate therapy.
Clostridium difficile–associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis, has been
reported with nearly all systemic antibacterial agents, including ZERBAXA. Careful medical history is necessary because CDAD has
been reported to occur more than two months after the administration of antibacterial agents. If CDAD is confirmed, antibacterial
use not directed against C. difficile should be discontinued, if possible.
Development of drug-resistant bacteria: Prescribing ZERBAXA in the absence of a proven or strongly suspected bacterial
infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Adverse reactions: The most common adverse reactions occurring in ≥5% of patients were headache (5.8%) in the cUTI trial,
and nausea (7.9%), diarrhea (6.2%) and pyrexia (5.6%) in the cIAI trial.
Merck’s commitment to infectious diseases
For more than 100 years, Merck has contributed to the discovery and development of novel medicines and vaccines to combat
infectious diseases. In addition to a combined portfolio of antibiotic, antiviral and antifungal medicines, vaccines, and medicines
for HIV and HCV, Merck has multiple programs that span discovery through late-stage development. Merck currently has eight
compounds in Phase 2/Phase 3 clinical trials for the potential treatment or prevention of infectious diseases.
About Merck
For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada,
has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our
prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than
140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care
through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the
prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic
diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information,
visit
www.merck.com and connect with us on
Twitter,
Facebook,
Instagram,
YouTube and
LinkedIn.
Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within
the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based
upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There
can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that
they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize,
actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors,
including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care
legislation in the United States and internationally; global trends toward health care cost containment; technological advances,
new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory
approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial
instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other
protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause results to differ materially from those described in the
forward-looking statements can be found in the company’s 2017 Annual Report on Form 10-K and the company’s other filings with the
Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Please see Prescribing Information for ZERBAXA (ceftolozane and tazobactam) at
http://www.merck.com/product/usa/pi_circulars/z/zerbaxa/zerbaxa_pi.pdf
Merck & Co., Inc.
Media:
Pam Eisele, 267-305-3558
Robert Consalvo, 908-295-0928
or
Investors:
Michael DeCarbo, 908-740-1807
View source version on businesswire.com: https://www.businesswire.com/news/home/20180911005151/en/